{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:55:38Z","timestamp":1780077338339,"version":"3.54.0"},"reference-count":125,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY10609"],"award-info":[{"award-number":["EY10609"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Peripherin 2 (Prph2) is a photoreceptor-specific tetraspanin protein present in the outer segment (OS) rims of rod and cone photoreceptors. It shares many common features with other tetraspanins, including a large intradiscal loop which contains several cysteines. This loop enables Prph2 to associate with itself to form homo-oligomers or with its homologue, rod outer segment membrane protein 1 (Rom1) to form hetero-tetramers and hetero-octamers. Mutations in PRPH2 cause a multitude of retinal diseases including autosomal dominant retinitis pigmentosa (RP) or cone dominant macular dystrophies. The importance of Prph2 for photoreceptor development, maintenance and function is underscored by the fact that its absence results in a failure to initialize OS formation in rods and formation of severely disorganized OS membranous structures in cones. Although the exact role of Rom1 has not been well studied, it has been concluded that it is not necessary for disc morphogenesis but is required for fine tuning OS disc size and structure. Pathogenic mutations in PRPH2 often result in complex and multifactorial phenotypes, involving not just photoreceptors, as has historically been reasoned, but also secondary effects on the retinal pigment epithelium (RPE) and retinal\/choroidal vasculature. The ability of Prph2 to form complexes was identified as a key requirement for the development and maintenance of OS structure and function. Studies using mouse models of pathogenic Prph2 mutations established a connection between changes in complex formation and disease phenotypes. Although progress has been made in the development of therapeutic approaches for retinal diseases in general, the highly complex interplay of functions mediated by Prph2 and the precise regulation of these complexes made it difficult, thus far, to develop a suitable Prph2-specific therapy. Here we describe the latest results obtained in Prph2-associated research and how mouse models provided new insights into the pathogenesis of its related diseases. Furthermore, we give an overview on the current status of the development of therapeutic solutions.<\/jats:p>","DOI":"10.3390\/cells9030784","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T13:04:04Z","timestamp":1585055044000},"page":"784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Interplay between Peripherin 2 Complex Formation and Degenerative Retinal Diseases"],"prefix":"10.3390","volume":"9","author":[{"given":"Lars","family":"Tebbe","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mashal","family":"Kakakhel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa S.","family":"Makia","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muayyad R.","family":"Al-Ubaidi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muna I.","family":"Naash","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/nrm1736","article-title":"Tetraspanin functions and associated microdomains","volume":"6","author":"Hemler","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/nri1548","article-title":"The tetraspanin web modulates immune-signalling complexes","volume":"5","author":"Levy","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","first-page":"3641","article-title":"Tetraspanins at a glance","volume":"127","author":"Charrin","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1042\/BST20160284","article-title":"Molecular interactions shaping the tetraspanin web","volume":"45","author":"Dunlock","year":"2017","journal-title":"Biochem. Soc. Trans."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/PL00000933","article-title":"Tetraspanins","volume":"58","author":"Boucheix","year":"2001","journal-title":"Cell. Mol. Life Sci. Cmls"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1146\/annurev.cellbio.19.111301.153609","article-title":"Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain","volume":"19","author":"Hemler","year":"2003","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/emboj\/20.1.12","article-title":"CD81 extracellular domain 3D structure: Insight into the tetraspanin superfamily structural motifs","volume":"20","author":"Kitadokoro","year":"2001","journal-title":"Embo. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.mcn.2018.04.001","article-title":"Tetraspanins shape the synapse","volume":"91","author":"Murru","year":"2018","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0968-0004(02)00014-2","article-title":"Functional domains in tetraspanin proteins","volume":"28","author":"Stipp","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.ympev.2010.02.015","article-title":"Evolution of cysteine patterns in the large extracellular loop of tetraspanins from animals, fungi, plants and single-celled eukaryotes","volume":"56","author":"DeSalle","year":"2010","journal-title":"Mol. Phylogenetics Evol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1083\/jcb.200404100","article-title":"Palmitoylation supports assembly and function of integrin-tetraspanin complexes","volume":"167","author":"Yang","year":"2004","journal-title":"J. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/S0014-5793(00)01240-0","article-title":"CD63 associates with CD11\/CD18 in large detergent-resistant complexes after translocation to the cell surface in human neutrophils","volume":"469","author":"Skubitz","year":"2000","journal-title":"Febs Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7974","DOI":"10.1074\/jbc.M008650200","article-title":"Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts","volume":"276","author":"Claas","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1083\/jcb.200108061","article-title":"Specific tetraspanin functions","volume":"155","author":"Hemler","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_15","first-page":"50","article-title":"Peripherin. A rim-specific membrane protein of rod outer segment discs","volume":"28","author":"Molday","year":"1987","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8118","DOI":"10.1523\/JNEUROSCI.17-21-08118.1997","article-title":"The effect of peripherin\/rds haploinsufficiency on rod and cone photoreceptors","volume":"17","author":"Cheng","year":"1997","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1083\/jcb.116.3.659","article-title":"Localization of peripherin\/rds in the disk membranes of cone and rod photoreceptors: Relationship to disk membrane morphogenesis and retinal degeneration","volume":"116","author":"Arikawa","year":"1992","journal-title":"J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13191","DOI":"10.1074\/jbc.C900853199","article-title":"Peripherin\/rds influences membrane vesicle morphology. Implications for retinopathies","volume":"275","author":"Wrigley","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0076-6879(00)16717-5","article-title":"Fusion between retinal rod outer segment membranes and model membranes: Functional assays and role for peripherin\/rds","volume":"316","year":"2000","journal-title":"Methods Enzymol."},{"key":"ref_20","first-page":"456","article-title":"Nonviral ocular gene therapy: Assessment and future directions","volume":"10","author":"Conley","year":"2008","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6144","DOI":"10.1021\/bi960259n","article-title":"Subunit composition of the peripherin\/rds-rom-1 disk rim complex from rod photoreceptors: Hydrodynamic evidence for a tetrameric quaternary structure","volume":"35","author":"Goldberg","year":"1996","journal-title":"Biochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4897","DOI":"10.1021\/bi048414i","article-title":"Role of the second intradiscal loop of peripherin\/rds in homo and hetero associations","volume":"44","author":"Ding","year":"2005","journal-title":"Biochemistry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4799","DOI":"10.1093\/hmg\/ddq410","article-title":"Differences in RDS trafficking, assembly and function in cones versus rods: Insights from studies of C150S-RDS","volume":"19","author":"Chakraborty","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/0896-6273(92)90137-3","article-title":"Cloning of the cDNA for a novel photoreceptor membrane protein (rom-1) identifies a disk rim protein family implicated in human retinopathies","volume":"8","author":"Bascom","year":"1992","journal-title":"Neuron"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"36272","DOI":"10.1074\/jbc.M113.520700","article-title":"Structural and functional analysis of the native peripherin-ROM1 complex isolated from photoreceptor cells","volume":"288","author":"Kevany","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.preteyeres.2015.12.002","article-title":"PRPH2\/RDS and ROM-1: Historical context, current views and future considerations","volume":"52","author":"Stuck","year":"2016","journal-title":"Prog Retin Eye Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/75621","article-title":"Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis","volume":"25","author":"Clarke","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1093\/hmg\/ddn406","article-title":"Differential requirements for retinal degeneration slow intermolecular disulfide-linked oligomerization in rods versus cones","volume":"18","author":"Chakraborty","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.preteyeres.2008.01.002","article-title":"The spectrum of retinal dystrophies caused by mutations in the peripherin\/RDS gene","volume":"27","author":"Boon","year":"2008","journal-title":"Prog Retin Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1136\/bjo.2004.062695","article-title":"Genetic and phenotypic heterogeneity in pattern dystrophy","volume":"89","author":"Francis","year":"2005","journal-title":"Br. J. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.3928\/23258160-20161130-05","article-title":"High-Resolution Adaptive Optics Retinal Image Analysis at Early Stage Central Areolar Choroidal Dystrophy With PRPH2 Mutation","volume":"47","author":"Gocho","year":"2016","journal-title":"Ophthalmic Surg. Lasers Imaging Retin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/cne.902240107","article-title":"Development and degeneration of retina in rds mutant mice: Electron microscopy","volume":"224","author":"Jansen","year":"1984","journal-title":"J. Comp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1083\/jcb.201608081","article-title":"Photoreceptor discs form through peripherin-dependent suppression of ciliary ectosome release","volume":"216","author":"Salinas","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_34","first-page":"459","article-title":"Prph2 initiates outer segment morphogenesis but maturation requires Prph2\/Rom1 oligomerization","volume":"28","author":"Conley","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.preteyeres.2017.05.001","article-title":"Cilia - The sensory antennae in the eye","volume":"60","author":"Wolfrum","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1083\/jcb.15.2.363","article-title":"Centrioles and the formation of rudimentary cilia by fibroblasts and smooth muscle cells","volume":"15","author":"Sorokin","year":"1962","journal-title":"J. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1042\/BC20110034","article-title":"Intraflagellar transport proteins in ciliogenesis of photoreceptor cells","volume":"103","author":"Sedmak","year":"2011","journal-title":"Biol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.preteyeres.2013.03.002","article-title":"Protein sorting, targeting and trafficking in photoreceptor cells","volume":"36","author":"Pearring","year":"2013","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chakraborty, D., Conley, S.M., Al-Ubaidi, M.R., and Naash, M.I. (2014). Initiation of rod outer segment disc formation requires RDS. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098939"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.cub.2014.01.002","article-title":"C. elegans ciliated sensory neurons release extracellular vesicles that function in animal communication","volume":"24","author":"Wang","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Cao, M., Ning, J., Hernandez-Lara, C.I., Belzile, O., Wang, Q., Dutcher, S.K., Liu, Y., and Snell, W.J. (2015). Uni-directional ciliary membrane protein trafficking by a cytoplasmic retrograde IFT motor and ciliary ectosome shedding. eLife, 4.","DOI":"10.7554\/eLife.05242"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10571-016-0345-4","article-title":"Ciliary Extracellular Vesicles: Txt Msg Organelles","volume":"36","author":"Wang","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.cell.2016.11.036","article-title":"An Actin Network Dispatches Ciliary GPCRs into Extracellular Vesicles to Modulate Signaling","volume":"168","author":"Nager","year":"2017","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.cell.2016.12.032","article-title":"Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision","volume":"168","author":"Phua","year":"2017","journal-title":"Cell"},{"key":"ref_45","first-page":"9477","article-title":"Fusion between retinal rod outer segment membranes and model membranes: A role for photoreceptor peripherin\/rds Peripherin\/rds fusogenic function correlates with subunit assembly An inducible amphipathic helix within the intrinsically disordered C terminus can participate in membrane curvature generation by peripherin-2\/rds","volume":"37","author":"Lamba","year":"1998","journal-title":"Biochemistry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1006\/exer.2002.2004","article-title":"Peripherin\/rds fusogenic function correlates with subunit assembly","volume":"75","author":"Stefano","year":"2002","journal-title":"Exp. Eye Res."},{"key":"ref_47","first-page":"4659","article-title":"Membrane curvature generation by a C-terminal amphipathic helix in peripherin-2\/rds, a tetraspanin required for photoreceptor sensory cilium morphogenesis","volume":"126","author":"Khattree","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7850","DOI":"10.1074\/jbc.M116.768143","article-title":"An inducible amphipathic helix within the intrinsically disordered C terminus can participate in membrane curvature generation by peripherin-2\/rds","volume":"292","author":"Milstein","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1002\/cne.901900307","article-title":"Disc morphogenesis in vertebrate photoreceptors","volume":"190","author":"Steinberg","year":"1980","journal-title":"J. Comp. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1083\/jcb.201508093","article-title":"Discs of mammalian rod photoreceptors form through the membrane evagination mechanism","volume":"211","author":"Ding","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5013","DOI":"10.1182\/blood.V90.12.5013","article-title":"A novel five-transmembrane hematopoietic stem cell antigen: Isolation, characterization, and molecular cloning","volume":"90","author":"Miraglia","year":"1997","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12425","DOI":"10.1073\/pnas.94.23.12425","article-title":"Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells","volume":"94","author":"Weigmann","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5002","DOI":"10.1182\/blood.V90.12.5002","article-title":"AC133, a novel marker for human hematopoietic stem and progenitor cells","volume":"90","author":"Yin","year":"1997","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/hmg\/9.1.27","article-title":"A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration","volume":"9","author":"Maw","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1167\/iovs.11-8635","article-title":"Prominin-1 localizes to the open rims of outer segment lamellae in Xenopus laevis rod and cone photoreceptors","volume":"53","author":"Han","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_56","first-page":"2908","article-title":"Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice","volume":"118","author":"Yang","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1523\/JNEUROSCI.2034-08.2009","article-title":"Loss of the cholesterol-binding protein prominin-1\/CD133 causes disk dysmorphogenesis and photoreceptor degeneration","volume":"29","author":"Zacchigna","year":"2009","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1167\/iovs.19-26993","article-title":"Characteristic Ocular Features in Cases of Autosomal Recessive PROM1 Cone-Rod Dystrophy","volume":"60","author":"Collison","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s00417-018-04206-w","article-title":"Identification of novel PROM1 mutations responsible for autosomal recessive maculopathy with rod-cone dystrophy","volume":"257","author":"Liang","year":"2019","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/S0955-0674(00)00239-8","article-title":"Implications of lipid microdomains for membrane curvature, budding and fission","volume":"13","author":"Huttner","year":"2001","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.jtbi.2005.09.020","article-title":"Curvature-induced accumulation of anisotropic membrane components and raft formation in cylindrical membrane protrusions","volume":"240","author":"Iglic","year":"2006","journal-title":"J. Theor. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/0042-6989(70)90001-5","article-title":"Further studies on the question of the patency of saccules in outer segments of vertebrate photoreceptors","volume":"10","author":"Cohen","year":"1970","journal-title":"Vis. Res."},{"key":"ref_63","first-page":"117","article-title":"Mammalian cones: Disc shedding, phagocytosis, and renewal","volume":"17","author":"Anderson","year":"1978","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_64","first-page":"90","article-title":"Fine structure and radioautography of rabbit photoreceptor cells","volume":"17","author":"Bunt","year":"1978","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/cne.901880204","article-title":"Rods and cones in the mouse retina. I. Structural analysis using light and electron microscopy","volume":"188","author":"LaVail","year":"1979","journal-title":"J. Comp. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/ng774","article-title":"Nrl is required for rod photoreceptor development","volume":"29","author":"Mears","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1167\/iovs.04-1427","article-title":"Cone-like morphological, molecular, and electrophysiological features of the photoreceptors of the Nrl knockout mouse","volume":"46","author":"Daniele","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.1096\/fj.14-251397","article-title":"Rim formation is not a prerequisite for distribution of cone photoreceptor outer segment proteins","volume":"28","author":"Conley","year":"2014","journal-title":"FASEB J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1083\/jcb.200509036","article-title":"Retention of function without normal disc morphogenesis occurs in cone but not rod photoreceptors","volume":"173","author":"Farjo","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_70","first-page":"352","article-title":"Molecular cloning, membrane topology, and localization of bovine rom-1 in rod and cone photoreceptor cells","volume":"37","author":"Moritz","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s00018-011-0736-0","article-title":"Structural and functional relationships between photoreceptor tetraspanins and other superfamily members","volume":"69","author":"Conley","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5370","DOI":"10.1074\/jbc.275.8.5370","article-title":"Disulfide-mediated oligomerization of Peripherin\/Rds and Rom-1 in photoreceptor disk membranes. Implications for photoreceptor outer segment morphogenesis and degeneration","volume":"275","author":"Loewen","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1523\/JNEUROSCI.3437-13.2014","article-title":"An unconventional secretory pathway mediates the cilia targeting of peripherin\/rds","volume":"34","author":"Tian","year":"2014","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1021\/bi701807c","article-title":"Outer segment oligomerization of Rds: Evidence from mouse models and subcellular fractionation","volume":"47","author":"Chakraborty","year":"2008","journal-title":"Biochemistry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"27901","DOI":"10.1074\/jbc.M115.683698","article-title":"Retinal Degeneration Slow (RDS) Glycosylation Plays a Role in Cone Function and in the Regulation of RDS.ROM-1 Protein Complex Formation","volume":"290","author":"Stuck","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1096\/fj.201901888R","article-title":"Novel molecular mechanisms for Prph2-associated pattern dystrophy","volume":"34","author":"Chakraborty","year":"2020","journal-title":"FASEB J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1021\/bi972036i","article-title":"Cysteine residues of photoreceptor peripherin\/rds: Role in subunit assembly and autosomal dominant retinitis pigmentosa","volume":"37","author":"Goldberg","year":"1998","journal-title":"Biochemistry"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1093\/hmg\/ddy240","article-title":"Oligomerization of Prph2 and Rom1 is essential for photoreceptor outer segment formation","volume":"27","author":"Zulliger","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3500","DOI":"10.1093\/hmg\/ddw193","article-title":"The K153Del PRPH2 mutation differentially impacts photoreceptor structure and function","volume":"25","author":"Chakraborty","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1001\/archopht.1993.01090110097033","article-title":"Phenotypic variation including retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in a single family with a deletion of codon 153 or 154 of the peripherin\/RDS gene","volume":"111","author":"Weleber","year":"1993","journal-title":"Arch. Ophthalmol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.1093\/hmg\/ddu014","article-title":"Insights into the mechanisms of macular degeneration associated with the R172W mutation in RDS","volume":"23","author":"Conley","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6260","DOI":"10.1093\/hmg\/ddu345","article-title":"The Y141C knockin mutation in RDS leads to complex phenotypes in the mouse","volume":"23","author":"Stuck","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3570","DOI":"10.1167\/iovs.02-1287","article-title":"Late-onset autosomal dominant macular dystrophy with choroidal neovascularization and nonexudative maculopathy associated with mutation in the RDS gene","volume":"44","author":"Khani","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_84","first-page":"498","article-title":"Generation and analysis of transgenic mice expressing P216L-substituted rds\/peripherin in rod photoreceptors","volume":"38","author":"Kedzierski","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1042\/BJ20041960","article-title":"The Cys214\u2192Ser mutation in peripherin\/rds causes a loss-of-function phenotype in transgenic mice","volume":"388","author":"Stricker","year":"2005","journal-title":"Biochem. J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1093\/hmg\/ddh211","article-title":"The R172W mutation in peripherin\/rds causes a cone-rod dystrophy in transgenic mice","volume":"13","author":"Ding","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5397","DOI":"10.1167\/iovs.07-0663","article-title":"Late-onset cone photoreceptor degeneration induced by R172W mutation in Rds and partial rescue by gene supplementation","volume":"48","author":"Conley","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_88","first-page":"509","article-title":"Rom1 converts Y141C-Prph2-associated pattern dystrophy to retinitis pigmentosa","volume":"26","author":"Conley","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1046\/j.1471-4159.1999.0720430.x","article-title":"Transgenic analysis of rds\/peripherin N-glycosylation: Effect on dimerization, interaction with rom1, and rescue of the rds null phenotype","volume":"72","author":"Kedzierski","year":"1999","journal-title":"J. Neurochem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"48009","DOI":"10.1074\/jbc.M108941200","article-title":"The cGMP-gated channel and related glutamic acid-rich proteins interact with peripherin-2 at the rim region of rod photoreceptor disc membranes","volume":"276","author":"Poetsch","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"11231","DOI":"10.1523\/JNEUROSCI.2875-11.2011","article-title":"In situ visualization of protein interactions in sensory neurons: Glutamic acid-rich proteins (GARPs) play differential roles for photoreceptor outer segment scaffolding","volume":"31","author":"Ritter","year":"2011","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1242\/jcs.042531","article-title":"Knockout of GARPs and the beta-subunit of the rod cGMP-gated channel disrupts disk morphogenesis and rod outer segment structural integrity","volume":"122","author":"Zhang","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.cell.2012.10.038","article-title":"Three-dimensional architecture of the rod sensory cilium and its disruption in retinal neurodegeneration","volume":"151","author":"Gilliam","year":"2012","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"5989","DOI":"10.1093\/hmg\/ddu323","article-title":"Peripherin-2 couples rhodopsin to the CNG channel in outer segments of rod photoreceptors","volume":"23","author":"Becirovic","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1167\/iovs.15-18516","article-title":"Role of RDS and Rhodopsin in Cngb1-Related Retinal Degeneration","volume":"57","author":"Chakraborty","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/S0161-6420(94)31377-7","article-title":"Macular dystrophy associated with mutations at codon 172 in the human retinal degeneration slow gene","volume":"101","author":"Wroblewski","year":"1994","journal-title":"Ophthalmology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3109\/13816819609057891","article-title":"Full characterization of the maculopathy associated with an Arg-172-Trp mutation in the RDS\/peripherin gene","volume":"17","author":"Piguet","year":"1996","journal-title":"Ophthalmic Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1086\/301679","article-title":"Founder effect, seen in the British population, of the 172 peripherin\/RDS mutation-and further refinement of genetic positioning of the peripherin\/RDS gene","volume":"62","author":"Payne","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1001\/archopht.117.10.1373","article-title":"Clinical features of codon 172 RDS macular dystrophy: Similar phenotype in 12 families","volume":"117","author":"Downes","year":"1999","journal-title":"Arch. Ophthalmol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/BF00216463","article-title":"A novel Cys-214-Ser mutation in the peripherin\/RDS gene in a Japanese family with autosomal dominant retinitis pigmentosa","volume":"92","author":"Saga","year":"1993","journal-title":"Hum. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/354480a0","article-title":"Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa","volume":"354","author":"Kajiwara","year":"1991","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1126\/science.8202715","article-title":"Digenic retinitis pigmentosa due to mutations at the unlinked peripherin\/RDS and ROM1 loci","volume":"264","author":"Kajiwara","year":"1994","journal-title":"Science"},{"key":"ref_103","first-page":"1972","article-title":"Dominant and digenic mutations in the peripherin\/RDS and ROM1 genes in retinitis pigmentosa","volume":"38","author":"Dryja","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"7718","DOI":"10.1073\/pnas.141124198","article-title":"Deficiency of rds\/peripherin causes photoreceptor death in mouse models of digenic and dominant retinitis pigmentosa","volume":"98","author":"Kedzierski","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1167\/iovs.04-0065","article-title":"Modulating expression of peripherin\/rds in transgenic mice: Critical levels and the effect of overexpression","volume":"45","author":"Nour","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1136\/bjo.79.1.28","article-title":"Extensive intrafamilial and interfamilial phenotypic variation among patients with autosomal dominant retinal dystrophy and mutations in the human RDS\/peripherin gene","volume":"79","author":"Theischen","year":"1995","journal-title":"Br. J. Ophthalmol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1093\/hmg\/11.9.1005","article-title":"Murine model of autosomal dominant retinitis pigmentosa generated by targeted deletion at codon 307 of the rds-peripherin gene","volume":"11","author":"McNally","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/ng0393-202","article-title":"Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene","volume":"3","author":"Nichols","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1001\/archopht.1996.01100130444016","article-title":"Deletion in the peripherin\/RDS gene in two unrelated Sardinian families with autosomal dominant butterfly-shaped macular dystrophy","volume":"114","author":"Fossarello","year":"1996","journal-title":"Arch. Ophthalmol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1001\/archopht.120.4.485","article-title":"Butterfly-shaped pattern dystrophy: A genetic, clinical, and histopathological report","volume":"120","author":"Zhang","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e0138508","DOI":"10.1371\/journal.pone.0138508","article-title":"SNAREs Interact with Retinal Degeneration Slow and Rod Outer Segment Membrane Protein-1 during Conventional and Unconventional Outer Segment Targeting","volume":"10","author":"Zulliger","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0896-6273(92)90226-4","article-title":"Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal degeneration slow (rds) mice","volume":"9","author":"Travis","year":"1992","journal-title":"Neuron"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/77068","article-title":"Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy","volume":"25","author":"Ali","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1002\/jgm.401","article-title":"Long-term evaluation of retinal function in Prph2Rd2\/Rd2 mice following AAV-mediated gene replacement therapy","volume":"5","author":"Schlichtenbrede","year":"2003","journal-title":"J. Gene Med."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Ding, X.Q., Quiambao, A.B., Fitzgerald, J.B., Cooper, M.J., Conley, S.M., and Naash, M.I. (2009). Ocular delivery of compacted DNA-nanoparticles does not elicit toxicity in the mouse retina. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007410"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1096\/fj.09-139147","article-title":"Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA nanoparticles results in improved phenotype in a mouse model of retinitis pigmentosa","volume":"24","author":"Cai","year":"2010","journal-title":"FASEB J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1172\/JCI64833","article-title":"DNA nanoparticle-mediated ABCA4 delivery rescues Stargardt dystrophy in mice","volume":"122","author":"Han","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Han, Z., Conley, S.M., Makkia, R., Guo, J., Cooper, M.J., and Naash, M.I. (2012). Comparative analysis of DNA nanoparticles and AAVs for ocular gene delivery. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052189"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"521","DOI":"10.2217\/nnm.11.158","article-title":"Direct gene transfer with compacted DNA nanoparticles in retinal pigment epithelial cells: Expression, repeat delivery and lack of toxicity","volume":"7","author":"Han","year":"2012","journal-title":"Nanomedicine"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"a017376","DOI":"10.1101\/cshperspect.a017376","article-title":"Gene therapy for PRPH2-associated ocular disease: Challenges and prospects","volume":"4","author":"Conley","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Cai, X., Nash, Z., Conley, S.M., Fliesler, S.J., Cooper, M.J., and Naash, M.I. (2009). A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005290"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1089\/hum.2011.213","article-title":"Long-term rescue of retinal structure and function by rhodopsin RNA replacement with a single adeno-associated viral vector in P23H RHO transgenic mice","volume":"23","author":"Mao","year":"2012","journal-title":"Hum. Gene Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"E8547","DOI":"10.1073\/pnas.1805055115","article-title":"Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector","volume":"115","author":"Cideciyan","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/humu.20287","article-title":"RNAi-based suppression and replacement of rds-peripherin in retinal organotypic culture","volume":"27","author":"Palfi","year":"2006","journal-title":"Hum. Mutat."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/978-1-4614-0631-0_29","article-title":"Suppression of rds expression by siRNA and gene replacement strategies for gene therapy using rAAV vector","volume":"723","author":"Yasumura","year":"2012","journal-title":"Adv. Exp. Med. Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/3\/784\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:10:59Z","timestamp":1760173859000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/3\/784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,24]]},"references-count":125,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["cells9030784"],"URL":"https:\/\/doi.org\/10.3390\/cells9030784","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,24]]}}}