{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:04:42Z","timestamp":1788365082125,"version":"build-2803163510"},"reference-count":210,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Melrose Personal Research Fund, Sydney, Australia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This narrative review outlines the structure and essential functions of ocular proteoglycans (PGs) in visual processing as documented in the extensive literature on this subject matter. The eye, as one of the most complex sensory organs, relies on the coordinated activity of various tissues and cell types, with PGs playing a central role in facilitating communication and maintaining tissue function. These molecules stabilise ocular tissues; for example, SPACRCAN (IMPG2) and hyaluronan aggregates in the interphotoreceptor matrix protect photoreceptors from oxidative stress. Specialised heparan sulfate PGs, such as pikachurin, eyes-shut, and the neurexin family, stabilise synapses and ensure synaptic specificity and plasticity. Pikachurin is particularly important for the rapid transmission of visual signals at the bipolar ribbon synapse. A diverse array of chondroitin sulfate (aggrecan, versican, neurocan, brevican, phosphacan, NG2), keratan sulfate (SV2), and heparan sulfate (perlecan, agrin, collagen XVIII) PGs are differentially expressed in ocular tissues, contributing to tissue stability and homeostasis. In the cornea, sclera, and choroid, small leucine-rich repeat PGs (SLRPs) maintain three-dimensional structure, corneal transparency, and tissue function through interactions with cytokines and growth factors. The vitreous humour contains opticin and nyctalopin, which support the nutrition of avascular regions and facilitate bipolar ribbon synapse signalling. Ultimately, the effectiveness of the eye as a visual organ depends significantly on the functional roles of its constituent PGs.<\/jats:p>","DOI":"10.3390\/ijms27041943","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T11:45:58Z","timestamp":1771415158000},"page":"1943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Structure and Function of Ocular Proteoglycans: Essential Proteins for Vision"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9237-0524","authenticated-orcid":false,"given":"James","family":"Melrose","sequence":"first","affiliation":[{"name":"Raymond Purves Bone and Joint Laboratory, Kolling Institute of Medical Research, The University of Sydney at Royal North Shore Hospital, Northern Sydney Local Health District, St. Leonards, Sydney, NSW 2065, Australia"},{"name":"Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1159\/000099236","article-title":"Anatomy and function of the eye","volume":"92","author":"Kaplan","year":"2007","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.clindermatol.2014.10.006","article-title":"Human ocular anatomy","volume":"33","author":"Kels","year":"2015","journal-title":"Clin. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/S0014-4835(03)00212-4","article-title":"Scleral structure, organisation and disease. A review","volume":"78","author":"Watson","year":"2004","journal-title":"Exp. Eye Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100773","DOI":"10.1016\/j.preteyeres.2019.100773","article-title":"Scleral structure and biomechanics","volume":"74","author":"Boote","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/j.1442-9071.2011.02745.x","article-title":"Anatomy of Tenons capsule","volume":"40","author":"Kakizaki","year":"2012","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.actbio.2020.06.026","article-title":"Collagen fiber interweaving is central to sclera stiffness","volume":"113","author":"Wang","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7528","DOI":"10.1167\/iovs.12-10797","article-title":"Mapping the differential distribution of proteoglycan core proteins in the adult human retina, choroid, and sclera","volume":"53","author":"Keenan","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1021\/bm0603746","article-title":"Fibrillogenesis of collagen types I, II, and III with small leucine-rich proteoglycans decorin and biglycan","volume":"7","author":"Douglas","year":"2006","journal-title":"Biomacromolecules"},{"key":"ref_9","first-page":"1057","article-title":"Small leucine rich repeat proteoglycans (SLRPs) in the human sclera: Identification of abundant levels of PRELP","volume":"12","author":"Johnson","year":"2006","journal-title":"Mol. Vis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1002\/pmic.201300255","article-title":"The human eye proteome project","volume":"13","author":"Omenn","year":"2013","journal-title":"Proteomics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1600340","DOI":"10.1002\/pmic.201600340","article-title":"The proteomes of the human eye, a highly compartmentalized organ","volume":"17","author":"Omenn","year":"2017","journal-title":"Proteomics"},{"key":"ref_12","first-page":"1740","article-title":"Proteoglycans in the human sclera. Evidence for the presence of aggrecan","volume":"38","author":"Rada","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","first-page":"1639","article-title":"Proteoglycan composition in the human sclera during growth and aging","volume":"41","author":"Rada","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0012-1606(91)90288-E","article-title":"Increased aggrecan (cartilage proteoglycan) production in the sclera of myopic chicks","volume":"147","author":"Rada","year":"1991","journal-title":"Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1167\/iovs.02-0783","article-title":"Ocular and scleral alterations in gene-targeted lumican-fibromodulin double-null mice","volume":"44","author":"Chakravarti","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.exer.2014.07.015","article-title":"The Dynamic Sclera: Extracellular Matrix Remodeling in Normal Ocular Growth and Myopia Development","volume":"133","author":"Harper","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"152239","DOI":"10.1016\/j.aanat.2024.152239","article-title":"The structure and function of the human choroid","volume":"254","author":"Zhang","year":"2024","journal-title":"Ann. Anat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.preteyeres.2009.12.002","article-title":"The multifunctional choroid","volume":"29","author":"Nickla","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101358","DOI":"10.1016\/j.preteyeres.2025.101358","article-title":"Characterizing Bruch\u2019s membrane: State-of-the-art imaging, computational segmentation, and biologic models in retinal disease and health","volume":"106","author":"Ong","year":"2025","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1177\/1120672120919337","article-title":"Bruch\u2019s membrane pathology: A mechanistic perspective","volume":"30","author":"Murali","year":"2020","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100803","DOI":"10.1016\/j.preteyeres.2019.100803","article-title":"Interactions of the choroid, Bruch\u2019s membrane, retinal pigment epithelium, and neurosensory retina collaborate to form the outer blood-retinal-barrier","volume":"76","author":"Fields","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2009.08.003","article-title":"The dynamic nature of Bruch\u2019s membrane","volume":"29","author":"Booij","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100416","DOI":"10.1016\/j.xops.2023.100416","article-title":"Bruch\u2019s Membrane Calcification in Pseudoxanthoma Elasticum: Comparing Histopathology and Clinical Imaging","volume":"4","author":"Risseeuw","year":"2023","journal-title":"Ophthalmol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bille, J.F. (2019). High Resolution Imaging in Microscopy and Ophthalmology: New Frontiers in Biomedical Optics, Springer.","DOI":"10.1007\/978-3-030-16638-0"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.jcrs.2010.12.037","article-title":"Anatomy and physiology of the cornea","volume":"37","author":"DelMonte","year":"2011","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jtos.2023.06.013","article-title":"Small leucine rich proteoglycans: Biology, function and their therapeutic potential in the ocular surface","volume":"29","author":"Gesteira","year":"2023","journal-title":"Ocul. Surf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0369-8114(01)00144-4","article-title":"Corneal collagens","volume":"49","author":"Robert","year":"2001","journal-title":"Pathol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.exer.2014.06.015","article-title":"Characterization of full-length recombinant human Proteoglycan 4 as an ocular surface boundary lubricant","volume":"127","author":"Samsom","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2017.05.006","article-title":"Degradation of proteoglycan 4\/lubricin by cathepsin S: Potential mechanism for diminished ocular surface lubrication in Sj\u00f6gren\u2019s syndrome","volume":"161","author":"Regmi","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"108628","DOI":"10.1016\/j.exer.2021.108628","article-title":"Proteoglycan 4 (PRG4) expression and function in dry eye associated inflammation","volume":"208","author":"Menon","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Puri, S., Coulson-Thomas, Y.M., Gesteira, T.F., and Coulson-Thomas, V.J. (2020). Distribution and Function of Glycosaminoglycans and Proteoglycans in the Development, Homeostasis and Pathology of the Ocular Surface. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00731"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Carrasco, R., and Sharma, A. (2025). Ocular surface glycocalyx in health and disease. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1561324"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jtos.2016.03.003","article-title":"Ocular Surface Membrane-Associated Mucins","volume":"14","author":"Ablamowicz","year":"2016","journal-title":"Ocul. Surf."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2015.07.001","article-title":"Corneal structure and transparency","volume":"49","author":"Meek","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100140","DOI":"10.1016\/j.medntd.2022.100140","article-title":"Corneal and scleral biomechanics in ophthalmic diseases: An updated review","volume":"15","author":"Wang","year":"2022","journal-title":"Med. Nov. Technol. Devices"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e35313","DOI":"10.1016\/j.heliyon.2024.e35313","article-title":"Collagen is crucial target protein for scleral remodeling and biomechanical change in myopia progression and control","volume":"10","author":"Sun","year":"2024","journal-title":"Heliyon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e20","DOI":"10.1002\/pgr2.20","article-title":"Clearing the light path: Proteoglycans and their important roles in the lens and cornea","volume":"2","author":"Stepp","year":"2024","journal-title":"Proteoglycan Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.exer.2016.08.015","article-title":"Small leucine-rich repeat proteoglycans in corneal inflammation and wound healing","volume":"151","author":"Frikeche","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s10792-024-03057-1","article-title":"Corneal biomechanics and diagnostics: A review","volume":"44","author":"Komninou","year":"2024","journal-title":"Int. Ophthalmol."},{"key":"ref_40","first-page":"26330040211003573","article-title":"Keratoconus: Cross-linking the window of the eye","volume":"2","author":"Hayes","year":"2021","journal-title":"Ther. Adv. Rare Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1167\/iovs.09-3738","article-title":"Mechanisms of corneal tissue cross-linking in response to treatment with topical riboflavin and long-wavelength ultraviolet radiation (UVA)","volume":"51","author":"McCall","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_42","first-page":"44","article-title":"A comprehensive review on corneal crosslinking","volume":"14","author":"Naranjo","year":"2024","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2174\/1874364101711010217","article-title":"Recent Innovations in Collagen Corneal Cross-linking; a Mini Review","volume":"11","author":"Vastardis","year":"2017","journal-title":"Open Ophthalmol. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.neuron.2012.10.002","article-title":"The neuronal organization of the retina","volume":"76","author":"Masland","year":"2012","journal-title":"Neuron"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.preteyeres.2014.06.003","article-title":"Functional architecture of the retina: Development and disease","volume":"42","author":"Hoon","year":"2014","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7282","DOI":"10.1038\/s41598-022-11204-w","article-title":"A comprehensive atlas of Aggrecan, Versican, Neurocan and Phosphacan expression across time in wildtype retina and in retinal degeneration","volume":"12","author":"Matsuyama","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-4835(02)00273-7","article-title":"SPACRCAN in the interphotoreceptor matrix of the mouse retina: Molecular, developmental and promoter analysis","volume":"76","author":"Chen","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6945","DOI":"10.1074\/jbc.275.10.6945","article-title":"SPACRCAN, a novel human interphotoreceptor matrix hyaluronan-binding proteoglycan synthesized by photoreceptors and pinealocytes","volume":"275","author":"Acharya","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Birbrair, A. (2019). Pericytes in the Retina. Pericyte Biology in Different Organs, Springer. Advances in Experimental Medicine and Biology.","DOI":"10.1007\/978-3-030-11093-2"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Yabuno, K., Morise, J., Kizuka, Y., Hashii, N., Kawasaki, N., Takahashi, S., Miyata, S., Izumikawa, T., Kitagawa, H., and Takematsu, H. (2015). A Sulfated Glycosaminoglycan Linkage Region is a Novel Type of Human Natural Killer-1 (HNK-1) Epitope Expressed on Aggrecan in Perineuronal Nets. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144560"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Low, S., Connor, T.B., Kassem, I.S., Costakos, D.M., and Chaurasia, S.S. (2021). Small Leucine-Rich Proteoglycans (SLRPs) in the Retina. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147293"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1440-169X.2012.01339.x","article-title":"Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance","volume":"54","author":"Dellett","year":"2012","journal-title":"Dev. Growth Differ."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1146\/annurev.ne.08.030185.002011","article-title":"Phototransduction in vertebrate rods","volume":"8","author":"Schwartz","year":"1985","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_54","unstructured":"Kolb, H., Fernandez, E., Jones, B., and Nelson, R. (1995). Photoreceptors. Webvision: The Organization of the Retina and Visual System, University of Utah Health Sciences Center."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1007\/s00424-021-02551-0","article-title":"Light responses of mammalian cones","volume":"473","author":"Fain","year":"2021","journal-title":"Pflugers Arch."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/j.1748-1716.2011.02355.x","article-title":"Structure and function of a complex sensory synapse","volume":"204","year":"2012","journal-title":"Acta Physiol."},{"key":"ref_57","first-page":"275","article-title":"Retinal phototransduction","volume":"19","author":"Mannu","year":"2014","journal-title":"Neurosciences"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00441-006-0234-0","article-title":"Ribbon synapses of the retina","volume":"326","author":"Dieck","year":"2006","journal-title":"Cell Tissue Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101116","DOI":"10.1016\/j.preteyeres.2022.101116","article-title":"Rhodopsin, light-sensor of vision","volume":"93","author":"Hofmann","year":"2023","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.bbabio.2013.08.009","article-title":"Cone visual pigments","volume":"1837","author":"Imamoto","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1350-9462(98)00024-X","article-title":"Matrix and the retinal pigment epithelium in proliferative retinal disease","volume":"18","author":"Hiscott","year":"1999","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"eadd9539","DOI":"10.1126\/scisignal.add9539","article-title":"Structure of the photoreceptor synaptic assembly of the extracellular matrix protein pikachurin with the orphan receptor GPR179","volume":"16","author":"Patil","year":"2023","journal-title":"Sci. Signal"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.neuron.2009.12.019","article-title":"LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation","volume":"64","author":"Sylwestrak","year":"2009","journal-title":"Neuron"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.neuron.2009.12.012","article-title":"LRRTM2 functions as a neurexin ligand in promoting excitatory synapse formation","volume":"64","author":"Ko","year":"2009","journal-title":"Neuron"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1038\/emboj.2010.123","article-title":"Structural insights into the exquisite selectivity of neurexin\/neuroligin synaptic interactions","volume":"29","author":"Leone","year":"2010","journal-title":"EMBO J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.sbi.2019.01.009","article-title":"Neurexins\u2014Versatile molecular platforms in the synaptic cleft","volume":"54","author":"Rudenko","year":"2019","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.1038\/s41467-018-06333-8","article-title":"Structural insights into modulation and selectivity of transsynaptic neurexin-LRRTM interaction","volume":"9","author":"Yamagata","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1016\/j.cell.2018.07.002","article-title":"Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships","volume":"174","author":"Zhang","year":"2018","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Frederick, C.E., and Zenisek, D. (2023). Ribbon Synapses and Retinal Disease: Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065090"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1152\/physrev.00026.2018","article-title":"Sensory Processing at Ribbon Synapses in the Retina and the Cochlea","volume":"100","author":"Moser","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1146\/annurev-vision-101322-111204","article-title":"Presynaptic Proteins and Their Roles in Visual Processing by the Retina","volume":"10","author":"Thoreson","year":"2024","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0896-6273(00)00159-8","article-title":"RIBEYE, a component of synaptic ribbons: A protein\u2019s journey through evolution provides insight into synaptic ribbon function","volume":"28","author":"Schmitz","year":"2000","journal-title":"Neuron"},{"key":"ref_73","first-page":"376","article-title":"Freeze-etching technique with simple rapid freezing of fresh biological specimen","volume":"29","author":"Usukura","year":"1980","journal-title":"J. Electron. Microsc."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.ajhg.2009.10.012","article-title":"Mutations in TRPM1 are a common cause of complete congenital stationary night blindness","volume":"85","author":"Bijveld","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/81619","article-title":"Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness","volume":"26","author":"Naylor","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/81627","article-title":"The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein","volume":"26","author":"Pusch","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/978-3-642-54215-2_15","article-title":"TRPM1","volume":"222","author":"Irie","year":"2014","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"11521","DOI":"10.1523\/JNEUROSCI.1682-11.2011","article-title":"TRPM1 forms complexes with nyctalopin in vivo and accumulates in postsynaptic compartment of ON-bipolar neurons in mGluR6-dependent manner","volume":"31","author":"Cao","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/1097-0029(20000715)50:2<141::AID-JEMT6>3.0.CO;2-B","article-title":"Presynaptic proteins of ribbon synapses in the retina","volume":"50","author":"Morgans","year":"2000","journal-title":"Microsc. Res. Tech."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1177\/1073858408331373","article-title":"The role of ribbons at sensory synapses","volume":"15","author":"LoGiudice","year":"2009","journal-title":"Neuroscientist"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1113\/JP274124","article-title":"Mutations in the voltage-sensing domain affect the alternative ion permeation pathway in the TRPM3 channel","volume":"596","author":"Held","year":"2018","journal-title":"J. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1042\/BST0350086","article-title":"Subunit interaction in channel assembly and functional regulation of transient receptor potential melastatin (TRPM) channels","volume":"35","author":"Jiang","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/nrn2924","article-title":"The diverse roles of ribbon synapses in sensory neurotransmission","volume":"11","author":"Matthews","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.preteyeres.2005.04.002","article-title":"Synaptic transmission at retinal ribbon synapses","volume":"24","author":"Heidelberger","year":"2005","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev-vision-082114-035709","article-title":"Ribbon Synapses and Visual Processing in the Retina","volume":"1","author":"Lagnado","year":"2015","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/bies.1118","article-title":"Structure suggests function: The case for synaptic ribbons as exocytotic nanomachines","volume":"23","author":"Lenzi","year":"2001","journal-title":"Bioessays"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/35008000","article-title":"Specificities of heparan sulphate proteoglycans in developmental processes","volume":"404","author":"Perrimon","year":"2000","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1038\/nature05817","article-title":"Heparan sulphate proteoglycans fine-tune mammalian physiology","volume":"446","author":"Bishop","year":"2007","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.vph.2013.12.002","article-title":"Potential roles of vessel wall heparan sulfate proteoglycans in atherosclerosis","volume":"60","author":"Madonna","year":"2014","journal-title":"Vasc. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"C1052","DOI":"10.1152\/ajpcell.00018.2022","article-title":"The role of the glypican and syndecan families of heparan sulfate proteoglycans in cardiovascular function and disease","volume":"323","author":"Thota","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6511","DOI":"10.1167\/iovs.11-7909","article-title":"Mapping the differential distribution of glycosaminoglycans in the adult human retina, choroid, and sclera","volume":"52","author":"Clark","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1076\/ceyr.22.3.190.5519","article-title":"Vascular localization of heparan sulfateproteoglycans in retinas of patients with diabetes mellitus and in VEGF-induced retinopathy using domain-specific antibodies","volume":"22","author":"Witmer","year":"2001","journal-title":"Curr. Eye Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1167\/iovs.62.14.5","article-title":"An Atlas of Heparan Sulfate Proteoglycans in the Postnatal Rat Lens","volume":"62","author":"Wishart","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/S0140-6736(22)02609-5","article-title":"Age-related macular degeneration","volume":"401","author":"Guymer","year":"2023","journal-title":"Lancet"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1097\/IAE.0000000000001575","article-title":"Choroidal Neovascularization","volume":"37","author":"Spaide","year":"2017","journal-title":"Retina"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.survophthal.2024.08.003","article-title":"Macular neovascularization","volume":"70","author":"Sheth","year":"2025","journal-title":"Surv. Ophthalmol."},{"key":"ref_97","first-page":"3974","article-title":"Mechanisms of retinal and choroidal neovascularization","volume":"35","year":"1994","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1007\/s00018-021-03796-9","article-title":"The complement system in age-related macular degeneration","volume":"78","author":"Armento","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1755-3768.2011.02295.x","article-title":"Complement system activation and endothelial dysfunction in patients with age-related macular degeneration (AMD): Possible relationship between AMD and atherosclerosis","volume":"90","author":"Kawa","year":"2012","journal-title":"Acta Ophthalmol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1167\/iovs.65.12.20","article-title":"Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration","volume":"65","author":"Tang","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1126\/science.1109557","article-title":"Complement factor H polymorphism in age-related macular degeneration","volume":"308","author":"Klein","year":"2005","journal-title":"Science"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/APO.0000000000000223","article-title":"Age-Related Macular Degeneration: Genetics and Biology","volume":"5","author":"Kumaramanickavel","year":"2016","journal-title":"Asia Pac. J. Ophthalmol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.preteyeres.2017.09.001","article-title":"Complement factor H in AMD: Bridging genetic associations and pathobiology","volume":"62","author":"Toomey","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4962","DOI":"10.4049\/jimmunol.1401613","article-title":"Identification of factor H-like protein 1 as the predominant complement regulator in Bruch\u2019s membrane: Implications for age-related macular degeneration","volume":"193","author":"Clark","year":"2014","journal-title":"J. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1159\/000356513","article-title":"The role of complement in age-related macular degeneration: Heparan sulphate, a ZIP code for complement factor H?","volume":"6","author":"Keenan","year":"2014","journal-title":"J. Innate Immun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"30192","DOI":"10.1074\/jbc.M110.103986","article-title":"Impaired binding of the age-related macular degeneration-associated complement factor H 402H allotype to Bruch\u2019s membrane in human retina","volume":"285","author":"Clark","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5370","DOI":"10.1167\/iovs.14-14126","article-title":"Age-dependent changes in heparan sulfate in human Bruch\u2019s membrane: Implications for age-related macular degeneration","volume":"55","author":"Keenan","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1369\/0022155420988661","article-title":"A Systems View of the Heparan Sulfate Interactome","volume":"69","author":"Sorrentino","year":"2021","journal-title":"J. Histochem. Cytochem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1042\/EBC20230093","article-title":"Interactions of proteins with heparan sulfate","volume":"68","author":"Alotaibi","year":"2024","journal-title":"Essays Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"19892","DOI":"10.1074\/jbc.M111.228114","article-title":"A systems biology approach for the investigation of the heparin\/heparan sulfate interactome","volume":"286","author":"Ori","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/emboj\/21.7.1535","article-title":"Lack of collagen XVIII\/endostatin results in eye abnormalities","volume":"21","author":"Fukai","year":"2002","journal-title":"EMBO J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/sj.emboj.7600014","article-title":"Collagen XVIII\/endostatin is essential for vision and retinal pigment epithelial function","volume":"23","author":"Marneros","year":"2004","journal-title":"EMBO J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1167\/iovs.03-0862","article-title":"Localization of collagen XVIII and the endostatin portion of collagen XVIII in aged human control eyes and eyes with age-related macular degeneration","volume":"45","author":"Bhutto","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/(SICI)1097-4695(199602)29:2<165::AID-NEU4>3.0.CO;2-8","article-title":"The developing avian retina expresses agrin isoforms during synaptogenesis","volume":"29","author":"Horton","year":"1996","journal-title":"J. Neurobiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1006\/mcne.1997.0651","article-title":"Differential distribution of agrin isoforms in the developing and adult avian retina","volume":"10","year":"1997","journal-title":"Mol. Cell Neurosci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1006\/dbio.1999.9410","article-title":"Synapse formation and agrin expression in stratospheroid cultures from embryonic chick retina","volume":"214","author":"Hering","year":"1999","journal-title":"Dev. Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"4188","DOI":"10.1046\/j.1460-9568.1999.00848.x","article-title":"Expression, distribution and ultrastructural localization of the synapse-organizing molecule agrin in the mature avian retina","volume":"11","author":"Koulen","year":"1999","journal-title":"Eur. J. Neurosci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3892\/ijmm.2024.5422","article-title":"Role of Agrin in tissue repair and regeneration: From mechanisms to therapeutic opportunities","volume":"54","author":"Li","year":"2024","journal-title":"Int. J. Mol. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/ar2957","article-title":"New role for Agrin in T cells and its potential importance in immune system regulation","volume":"12","author":"Jury","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"cwae051","DOI":"10.1093\/glycob\/cwae051","article-title":"Dystroglycan-HSPG interactions provide synaptic plasticity and specificity","volume":"34","author":"Melrose","year":"2024","journal-title":"Glycobiology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.celrep.2018.08.068","article-title":"Transsynaptic Binding of Orphan Receptor GPR179 to Dystroglycan-Pikachurin Complex Is Essential for the Synaptic Organization of Photoreceptors","volume":"25","author":"Orlandi","year":"2018","journal-title":"Cell Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/nn.2160","article-title":"Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation","volume":"11","author":"Sato","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"6126","DOI":"10.1523\/JNEUROSCI.0322-12.2012","article-title":"Presynaptic dystroglycan-pikachurin complex regulates the proper synaptic connection between retinal photoreceptor and bipolar cells","volume":"32","author":"Omori","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Alfano, G., Kruczek, P.M., Shah, A.Z., Kramarz, B., Jeffery, G., Zelhof, A.C., and Bhattacharya, S.S. (2016). EYS Is a Protein Associated with the Ciliary Axoneme in Rods and Cones. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166397"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/neu.10343","article-title":"Activity-driven sharpening of the retinotectal projection: The search for retrograde synaptic signaling pathways","volume":"59","author":"Schmidt","year":"2004","journal-title":"J. Neurobiol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"8150","DOI":"10.1523\/JNEUROSCI.1744-08.2008","article-title":"Developmental control of synaptic receptivity","volume":"28","author":"Barker","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.neuron.2012.11.012","article-title":"Neurexin regulates visual function via mediating retinoid transport to promote rhodopsin maturation","volume":"77","author":"Tian","year":"2013","journal-title":"Neuron"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1042\/bj2990497","article-title":"Extraction and characterisation of the tissue forms of collagen types II and IX from bovine vitreous","volume":"299","author":"Bishop","year":"1994","journal-title":"Biochem. J."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"6992","DOI":"10.1016\/S0021-9258(19)39249-X","article-title":"Occurrence in chick embryo vitreous humour of a type IX collagen proteoglycan with an extraordinarily large chondroitin sulphate chain and short \u03b11 polypeptide","volume":"265","author":"Yada","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1074\/jbc.275.3.2123","article-title":"Identification in vitreous and molecular cloning of opticin, a novel member of the family of leucine-rich repeat proteins of the extracellular matrix","volume":"275","author":"Reardon","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/sj.cr.7290106","article-title":"Structure and function of aggrecan","volume":"12","author":"Kiani","year":"2002","journal-title":"Cell Res."},{"key":"ref_132","first-page":"291","article-title":"Brain aggrecan","volume":"3","author":"Schwartz","year":"1996","journal-title":"Perspect. Dev. Neurobiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1369\/0022155420952902","article-title":"Aggrecan in Cardiovascular Development and Disease","volume":"68","author":"Koch","year":"2020","journal-title":"J. Histochem. Cytochem."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Hayes, A., and Melrose, J. (2020). Aggrecan, the Primary Weight-Bearing Cartilage Proteoglycan, Has Context-Dependent, Cell-Directive Properties in Embryonic Development and Neurogenesis: Aggrecan Glycan Side Chain Modifications Convey Interactive Biodiversity. Biomolecules, 10.","DOI":"10.3390\/biom10091244"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"642798","DOI":"10.1155\/2014\/642798","article-title":"Chondroitin sulfate proteoglycans: Structure-function relationship with implication in neural development and brain disorders","volume":"2014","author":"Avram","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1369\/0022155412464376","article-title":"The different roles of aggrecan interaction domains","volume":"60","author":"Aspberg","year":"2012","journal-title":"J. Histochem. Cytochem."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"C967","DOI":"10.1152\/ajpcell.00081.2022","article-title":"Aggrecan and versican: Two brothers close or apart","volume":"322","author":"Watanabe","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"32247","DOI":"10.1074\/jbc.271.50.32247","article-title":"Interaction of cartilage matrix protein with aggrecan. Increased covalent cross-linking with tissue maturation","volume":"271","author":"Hauser","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"24591","DOI":"10.1074\/jbc.M611390200","article-title":"Interaction of cartilage oligomeric matrix protein\/thrombospondin 5 with aggrecan","volume":"282","author":"Chen","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Melin F\u00fcrst, C., M\u00f6rgelin, M., Vadstrup, K., Heineg\u00e5rd, D., Aspberg, A., and Blom, A.M. (2013). The C-type lectin of the aggrecan G3 domain activates complement. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061407"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1369\/0022155420953922","article-title":"Versican: A Dynamic Regulator of the Extracellular Matrix","volume":"88","author":"Islam","year":"2020","journal-title":"J. Histochem. Cytochem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1369\/0022155420937098","article-title":"Versican and Versican-matrikines in Cancer Progression, Inflammation, and Immunity","volume":"68","author":"Papadas","year":"2020","journal-title":"J. Histochem. Cytochem."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1182\/blood-2016-06-721092","article-title":"Versican vs versikine: Tolerance vs attack","volume":"128","author":"Schmitt","year":"2016","journal-title":"Blood"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00018-020-03578-9","article-title":"Neural glycomics: The sweet side of nervous system functions","volume":"78","author":"Sytnyk","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"22957","DOI":"10.1074\/jbc.271.38.22957","article-title":"Structure of the HNK-1 carbohydrate epitope on bovine peripheral myelin glycoprotein P0","volume":"271","author":"Voshol","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1016\/j.bbagen.2017.06.025","article-title":"The role of human natural killer-1 (HNK-1) carbohydrate in neuronal plasticity and disease","volume":"1861","author":"Morise","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"27227","DOI":"10.1074\/jbc.C200296200","article-title":"Mice deficient in nervous system-specific carbohydrate epitope HNK-1 exhibit impaired synaptic plasticity and spatial learning","volume":"277","author":"Yamamoto","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.brainres.2015.06.003","article-title":"The role of the NG2 proteoglycan in OPC and CNS network function","volume":"1638","author":"Sakry","year":"2016","journal-title":"Brain Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/978-3-030-02601-1_2","article-title":"The NG2 Proteoglycan in Pericyte Biology","volume":"1109","author":"Stallcup","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"801","DOI":"10.4103\/1673-5374.353488","article-title":"Pathology-induced NG2 proteoglycan expression in microglia","volume":"18","author":"Meyer","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s40478-020-01016-2","article-title":"Acute brain injuries trigger microglia as an additional source of the proteoglycan NG2","volume":"8","author":"Huang","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"23142","DOI":"10.1074\/jbc.M401584200","article-title":"Spacrcan binding to hyaluronan and other glycosaminoglycans. Molecular and biochemical studies","volume":"279","author":"Chen","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e1800166","DOI":"10.1002\/bies.201800166","article-title":"Proteoglycan 4: From Mere Lubricant to Regulator of Tissue Homeostasis and Inflammation: Does proteoglycan 4 have the ability to buffer the inflammatory response?","volume":"41","author":"Das","year":"2019","journal-title":"Bioessays"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e2300090","DOI":"10.1002\/bies.202300090","article-title":"Emergence of proteoglycan-4, (lubricin) as a multifunctional, cell instructive, anti-inflammatory boundary lubricant","volume":"45","author":"Melrose","year":"2023","journal-title":"Bioessays"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Roggio, F., Petrigna, L., Trovato, B., Di Rosa, M., and Musumeci, G. (2023). The Role of Lubricin, Irisin and Exercise in the Prevention and Treatment of Osteoarthritis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065126"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1189\/jlb.1006629","article-title":"Hemopexin domains as multifunctional liganding modules in matrix metalloproteinases and other proteins","volume":"81","author":"Piccard","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Menon, N., Suhail, Y., Goyal, R., Du, W., Tanguay, A.P., Jay, G.D., Ghosh, M., and Kshitiz Schmidt, T.A. (2022). Recombinant Human Proteoglycan 4 (rhPRG4) Downregulates TNF\u03b1-Stimulated NF\u03baB Activity and FAT10 Expression in Human Corneal Epithelial Cells. Int. J. Mol. Sci., 23.","DOI":"10.1101\/2022.10.12.511806"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s00441-022-03647-4","article-title":"Proteoglycan 4 is present within the dura mater and produced by mesenchymal progenitor cells","volume":"389","author":"Mudigonda","year":"2022","journal-title":"Cell Tissue Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1073\/pnas.91.7.2512","article-title":"Phosphacan, a chondroitin sulfate proteoglycan of brain that interacts with neurons and neural cell-adhesion molecules, is an extracellular variant of a receptor-type protein tyrosine phosphatase","volume":"91","author":"Maurel","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/0-387-30128-3_3","article-title":"DSD-1-Proteoglycan\/Phosphacan and receptor protein tyrosine phosphatase-beta isoforms during development and regeneration of neural tissues","volume":"557","author":"Faissner","year":"2006","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0968-0004(98)01195-5","article-title":"Multi-ligand interactions with receptor-like protein tyrosine phosphatase beta: Implications for intercellular signaling","volume":"23","author":"Peles","year":"1998","journal-title":"Trends Biochem. Sci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s12079-009-0066-2","article-title":"The matricellular functions of small leucine-rich proteoglycans (SLRPs)","volume":"3","author":"Merline","year":"2009","journal-title":"J. Cell Commun. Signal"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"104","DOI":"10.33696\/Signaling.4.098","article-title":"Structural Insights into Protein-Ligand Interactions of Small Leucine Rich Repeat Proteoglycans with a Large Number of Binding Partners: An Overview","volume":"4","author":"Matsushima","year":"2023","journal-title":"J. Cell Signal"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"23744","DOI":"10.1074\/jbc.M116.730325","article-title":"The Tyrosine Sulfate Domain of Fibromodulin Binds Collagen and Enhances Fibril Formation","volume":"291","author":"Tillgren","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Smith, M., and Melrose, J. (2024). Lumican, a Multifunctional Cell Instructive Biomarker Proteoglycan Has Novel Roles as a Marker of the Hypercoagulative State of Long Covid Disease. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052825"},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Stasiak, M., Boncela, J., Perreau, C., Karamanou, K., Chatron-Colliet, A., Proult, I., Przygodzka, P., Chakravarti, S., Maquart, F.X., and Kowalska, M.A. (2016). Lumican Inhibits SNAIL-Induced Melanoma Cell Migration Specifically by Blocking MMP-14 Activity. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150226"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"4319","DOI":"10.1016\/j.febslet.2014.09.040","article-title":"Lumican: A new inhibitor of matrix metalloproteinase-14 activity","volume":"588","author":"Pietraszek","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1016\/j.febslet.2009.08.012","article-title":"Lumcorin: A leucine-rich repeat 9-derived peptide from human lumican inhibiting melanoma cell migration","volume":"583","author":"Zeltz","year":"2009","journal-title":"FEBS Lett."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Pietraszek, K., Br\u00e9zillon, S., Perreau, C., Malicka-B\u0142aszkiewicz, M., Maquart, F.X., and Wegrowski, Y. (2013). Lumican-derived peptides inhibit melanoma cell growth and migration. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076232"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Kao, W., Zhang, J., Venkatakrishnan, J., Chang, S.H., Yuan, Y., Yamanaka, O., Xia, Y., Gesteira, T.F., Verma, S., and Coulson-Thomas, V.J. (2024). Lumican\/Lumikine Promotes Healing of Corneal Epithelium Debridement by Upregulation of EGFR Ligand Expression via Noncanonical Smad-Independent TGF\u03b2\/TBRs Signaling. Cells, 13.","DOI":"10.3390\/cells13191599"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"42057","DOI":"10.1038\/srep42057","article-title":"Lumican Peptides: Rational Design Targeting ALK5\/TGFBRI","volume":"7","author":"Gesteira","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1074\/jbc.M112.430512","article-title":"The C-terminal peptide of chondroadherin modulates cellular activity by selectively binding to heparan sulfate chains","volume":"288","author":"Haglund","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"15061","DOI":"10.1074\/jbc.M108285200","article-title":"The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement membrane anchor","volume":"277","author":"Bengtsson","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"24634","DOI":"10.1038\/s41598-025-09018-7","article-title":"PRELP functions via multiple interactions with intrinsically weak affinity relying on ECM anchoring and remodeling","volume":"15","author":"Kosuge","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1083\/jcb.200906014","article-title":"The glycosaminoglycan-binding domain of PRELP acts as a cell type-specific NF-kappaB inhibitor that impairs osteoclastogenesis","volume":"187","author":"Rucci","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"a004952","DOI":"10.1101\/cshperspect.a004952","article-title":"Heparan sulfate proteoglycans","volume":"3","author":"Sarrazin","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1007\/s00018-009-0096-1","article-title":"Multifunctionality of extracellular and cell surface heparan sulfate proteoglycans","volume":"66","author":"Carson","year":"2009","journal-title":"Cell Mol. Life Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1007\/s00018-007-7455-6","article-title":"Serglycin\u2013structure and biology","volume":"65","author":"Kolset","year":"2008","journal-title":"Cell Mol. Life Sci."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Hayes, A., Farrugia, B.L., Biose, I.J., Bix, G.J., and Melrose, J. (2022). Perlecan, A Multi-Functional, Cell-Instructive, Matrix-Stabilizing Proteoglycan With Roles in Tissue Development Has Relevance to Connective Tissue Repair and Regeneration. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.856261"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Guilak, F., Hayes, A.J., and Melrose, J. (2021). Perlecan in Pericellular Mechanosensory Cell-Matrix Communication, Extracellular Matrix Stabilisation and Mechanoregulation of Load-Bearing Connective Tissues. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052716"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"105849","DOI":"10.1016\/j.biocel.2020.105849","article-title":"Perlecan, a modular instructive proteoglycan with diverse functional properties","volume":"128","author":"Melrose","year":"2020","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"11174","DOI":"10.1021\/bi8013938","article-title":"Diverse cell signaling events modulated by perlecan","volume":"47","author":"Whitelock","year":"2008","journal-title":"Biochemistry"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S1050-1738(00)00048-7","article-title":"Lipoprotein modulation of subendothelial heparan sulfate proteoglycans (perlecan) and atherogenicity","volume":"10","author":"Pillarisetti","year":"2000","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"7766","DOI":"10.1038\/s41598-018-25635-x","article-title":"Perlecan, a heparan sulfate proteoglycan, regulates systemic metabolism with dynamic changes in adipose tissue and skeletal muscle","volume":"8","author":"Yamashita","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"5486","DOI":"10.4049\/jimmunol.0903596","article-title":"Heparan sulfate, including that in Bruch\u2019s membrane, inhibits the complement alternative pathway: Implications for age-related macular degeneration","volume":"185","author":"Kelly","year":"2010","journal-title":"J. Immunol."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Hammadi, S., Tzoumas, N., Ferrara, M., Meschede, I.P., Lo, K., Harris, C., Lako, M., and Steel, D.H. (2023). Bruch\u2019s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration. J. Clin. Med., 12.","DOI":"10.3390\/jcm12082870"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"8763","DOI":"10.1073\/pnas.92.19.8763","article-title":"Mouse Col18a1 is expressed in a tissue-specific manner as three alternative variants and is localized in basement membrane zones","volume":"92","author":"Muragaki","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1097\/00001756-200208270-00001","article-title":"Agrin in the CNS: A protein in search of a function?","volume":"13","author":"Smith","year":"2002","journal-title":"Neuroreport"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.neuint.2012.02.028","article-title":"The role of agrin in synaptic development, plasticity and signaling in the central nervous system","volume":"61","author":"Daniels","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.biocel.2006.10.012","article-title":"Neural agrin: A synaptic stabiliser","volume":"39","author":"Ngo","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_191","first-page":"207","article-title":"Agrin in the developing CNS: New roles for a synapse organizer","volume":"17","year":"2002","journal-title":"News Physiol. Sci."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature22978","article-title":"The extracellular matrix protein agrin promotes heart regeneration in mice","volume":"547","author":"Bassat","year":"2017","journal-title":"Nature"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"e25361","DOI":"10.1002\/jnr.25361","article-title":"CNS\/PNS proteoglycans functionalize neuronal and astrocyte niche microenvironments optimizing cellular activity by preserving membrane polarization dynamics, ionic microenvironments, ion fluxes, neuronal activation, and network neurotransductive capacity","volume":"102","author":"Melrose","year":"2024","journal-title":"J. Neurosci. Res."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/febs.16251","article-title":"Role of neurexin heparan sulfate in the molecular assembly of synapses\u2014Expanding the neurexin code?","volume":"290","author":"Noborn","year":"2023","journal-title":"FEBS J."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Farrugia, B., and Melrose, J. (2023). The Glycosaminoglycan Side Chains and Modular Core Proteins of Heparan Sulphate Proteoglycans and the Varied Ways They Provide Tissue Protection by Regulating Physiological Processes and Cellular Behaviour. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814101"},{"key":"ref_196","first-page":"1616","article-title":"Spatiotemporal expression patterns of N-syndecan, a transmembrane heparan sulfate proteoglycan, in developing retina","volume":"43","author":"Inatani","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.celrep.2014.06.008","article-title":"Syndecan promotes axon regeneration by stabilizing growth cone migration","volume":"8","author":"Edwards","year":"2014","journal-title":"Cell Rep."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/iep.12112","article-title":"Fell-Muir Lecture: Syndecans: From peripheral coreceptors to mainstream regulators of cell behaviour","volume":"96","author":"Couchman","year":"2015","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3270001","article-title":"Syndecans: Multifunctional cell-surface co-receptors","volume":"327","author":"Carey","year":"1997","journal-title":"Biochem. J."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00441-009-0829-3","article-title":"Syndecans as receptors and organizers of the extracellular matrix","volume":"339","author":"Xian","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/BF01921737","article-title":"Syndecan family of cell surface proteoglycans: Developmentally regulated receptors for extracellular effector molecules","volume":"51","author":"Salmivirta","year":"1995","journal-title":"Experientia"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1111\/febs.14828","article-title":"Structures and interactions of syndecans","volume":"286","author":"Gondelaud","year":"2019","journal-title":"FEBS J."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1111\/febs.12174","article-title":"Mapping of matrix metalloproteinase cleavage sites on syndecan-1 and syndecan-4 ectodomains","volume":"280","author":"Multhaupt","year":"2013","journal-title":"FEBS J."},{"key":"ref_204","first-page":"347","article-title":"The glypican family of heparan sulfate proteoglycans: Major cell-surface proteoglycans of the developing nervous system","volume":"3","author":"Lander","year":"1996","journal-title":"Perspect. Dev. Neurobiol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.matbio.2013.12.007","article-title":"The role of glypicans in Hedgehog signaling","volume":"35","author":"Filmus","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1242\/dev.078402","article-title":"Dally and Notum regulate the switch between low and high level Hedgehog pathway signalling","volume":"139","author":"Ayers","year":"2012","journal-title":"Development"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.devcel.2008.03.006","article-title":"Glypican-3 inhibits Hedgehog signaling during development by competing with Patched for Hedgehog binding","volume":"14","author":"Capurro","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"17103","DOI":"10.1074\/jbc.M110.208082","article-title":"Novel contact-dependent bone morphogenetic protein (BMP) signaling mediated by heparan sulfate proteoglycans","volume":"286","author":"Dejima","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"7576","DOI":"10.1074\/jbc.M114.612705","article-title":"Processing by convertases is required for glypican-3-induced inhibition of Hedgehog signaling","volume":"290","author":"Capurro","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jprot.2016.08.017","article-title":"Mass spectrometry-based proteomics revealed Glypican-1 as a novel ADAM17 substrate","volume":"151","author":"Kawahara","year":"2017","journal-title":"J. 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