{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:19:54Z","timestamp":1791566394451,"version":"4.3.4"},"reference-count":79,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T00:00:00Z","timestamp":1721001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RC2788872"],"award-info":[{"award-number":["RC2788872"]}]},{"name":"Fondazione Roma (Italy)","award":["RC2788872"],"award-info":[{"award-number":["RC2788872"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previous studies reported the expression of toll-like receptors (TLRs), merely TLR2 and TLR4, and complement fragments (C3a, C5b9) in vitreoretinal disorders. Other than pathogens, TLRs can recognize endogenous products of tissue remodeling as damage-associated molecular pattern (DAMPs). The aim of this study was to confirm the expression of TLR2 and TLR4 in the fibrocellular membranes and vitreal fluids (soluble TLRs) of patients suffering of epiretinal membranes (ERMs) and assess their association with disease severity, complement fragments and inflammatory profiles. Twenty (n = 20) ERMs and twelve (n = 12) vitreous samples were collected at the time of the vitrectomy. Different severity-staged ERMs were processed for: immunolocalization (IF), transcriptomic (RT-PCR) and proteomics (ELISA, IP\/WB, Protein Chip Array) analysis. The investigation of targets included TLR2, TLR4, C3a, C5b9, a few selected inflammatory biomarkers (Eotaxin-2, Rantes, Vascular Endothelial Growth Factor (VEGFA), Vascular Endothelial Growth Factor receptor (VEGFR2), Interferon-\u03b3 (IFN\u03b3), Interleukin (IL1\u03b2, IL12p40\/p70)) and a restricted panel of matrix enzymes (Matrix metalloproteinases (MMPs)\/Tissue Inhibitor of Metallo-Proteinases (TIMPs)). A reduced cellularity was observed as function of ERM severity. TLR2, TLR4 and myD88 transcripts\/proteins were detected in membranes and decreased upon disease severity. The levels of soluble TLR2 and TLR4, as well as C3a, C5b9, Eotaxin-2, Rantes, VEGFA, VEGFR2, IFN\u03b3, IL1\u03b2, IL12p40\/p70, MMP7 and TIMP2 levels were changed in vitreal samples. Significant correlations were observed between TLRs and complement fragments and between TLRs and some inflammatory mediators. Our findings pointed at TLR2 and TLR4 over-expression at early stages of ERM formation, suggesting the participation of the local immune response in the severity of disease. These activations at the early-stage of ERM formation suggest a potential persistence of innate immune response in the early phases of fibrocellular membrane formation.<\/jats:p>","DOI":"10.3390\/ijms25147732","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T18:17:32Z","timestamp":1721067452000},"page":"7732","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["TLR2 and TLR4 Are Expressed in Epiretinal Membranes: Possible Links with Vitreous Levels of Complement Fragments and DAMP-Related Proteins"],"prefix":"10.3390","volume":"25","author":[{"given":"Lucia","family":"Dinice","sequence":"first","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8777-197X","authenticated-orcid":false,"given":"Graziana","family":"Esposito","sequence":"additional","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1793-9842","authenticated-orcid":false,"given":"Andrea","family":"Cacciamani","sequence":"additional","affiliation":[{"name":"Surgical Retina Research Unit, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-1647","authenticated-orcid":false,"given":"Bijorn Omar","family":"Balzamino","sequence":"additional","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Cosimi","sequence":"additional","affiliation":[{"name":"Surgical Retina Research Unit, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1401-8020","authenticated-orcid":false,"given":"Concetta","family":"Cafiero","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Unit, Fabrizio Spaziani Hospital, 03100 Frosinone, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Ripandelli","sequence":"additional","affiliation":[{"name":"Surgical Retina Research Unit, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9375-6071","authenticated-orcid":false,"given":"Alessandra","family":"Micera","sequence":"additional","affiliation":[{"name":"Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS\u2014Fondazione Bietti, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,15]]},"reference":[{"key":"ref_1","first-page":"91","article-title":"A Review of Last Decade Developments on Epiretinal Membrane Pathogenesis","volume":"9","author":"Tsotridou","year":"2020","journal-title":"Med. Hypothesis Discov. Innov. Ophthalmol."},{"key":"ref_2","first-page":"10","article-title":"An immunohistochemical study of IgG, complement C3, collagen type III and macrophage-marker Ki-M7 in epiretinal membranes","volume":"12","author":"Shi","year":"1996","journal-title":"Yan Ke Xue Bao"},{"key":"ref_3","first-page":"176","article-title":"Lymphocytes, macrophages and HLA-DR expression in vitreal and epiretinal membranes of proliferative vitreoretinopathy. An immunohistochemical study","volume":"1","author":"Tang","year":"1992","journal-title":"Ger. J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bianchi, L., Altera, A., Barone, V., Bonente, D., Bacci, T., De Benedetto, E., Bini, L., Tosi, G.M., Galvagni, F., and Bertelli, E. (2022). Untangling the Extracellular Matrix of Idiopathic Epiretinal Membrane: A Path Winding among Structure, Interactomics and Translational Medicine. Cells, 15.","DOI":"10.3390\/cells11162531"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hu, M., Ling, Z., and Ren, X. (2022). Extracellular matrix dynamics: Tracking in biological systems and their implications. J. Biol. Eng., 16.","DOI":"10.1186\/s13036-022-00292-x"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"971","DOI":"10.3109\/02713683.2015.1080282","article-title":"A Simple Spontaneous Vitreal Reflux Collecting Procedure During Intravitreal Injection: Set-Up and Validation Studies","volume":"41","author":"Cacciamani","year":"2016","journal-title":"Curr. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1007\/s00417-020-04685-w","article-title":"Osteopontin in vitreous and idiopathic epiretinal membranes","volume":"258","author":"Dinice","year":"2020","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1007\/s00417-021-05492-7","article-title":"Cellular components of the idiopathic epiretinal membrane","volume":"260","author":"Roda","year":"2022","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_9","first-page":"493043","article-title":"Osteopontin and other regulators of angiogenesis and fibrogenesis in the vitreous from patients with proliferative vitreoretinal disorders","volume":"2012","author":"Nawaz","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1189\/jlb.0306164","article-title":"DAMPs, PAMPs and alarmins: All we need to know about danger","volume":"81","author":"Bianchi","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.expneurol.2013.11.020","article-title":"Extracellular matrix regulation of inflammation in the healthy and injured spinal cord","volume":"258","author":"Gaudet","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1369\/0022155417740880","article-title":"Danger-Associated Molecular Patterns Derived From the Extracellular Matrix Provide Temporal Control of Innate Immunity","volume":"66","author":"Frevert","year":"2018","journal-title":"J. Histochem. Cytochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1189\/jlb.1209775","article-title":"Endogenous ligands of TLR2 and TLR4: Agonists or assistants?","volume":"87","author":"Clett","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_14","first-page":"1","article-title":"Insight into the mechanisms regulating immune homeostasis in health and disease","volume":"29","author":"Sirisinha","year":"2011","journal-title":"Asian Pac. J. Allergy Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1002\/jcp.25124","article-title":"Toll-Like Receptors and Tissue Remodeling: The Pro\/Cons Recent Findings","volume":"231","author":"Micera","year":"2016","journal-title":"J. Cell Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/35100529","article-title":"Toll-like receptors and innate immunity","volume":"1","author":"Medzhitov","year":"2001","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","first-page":"1098","article-title":"Toll-Like Receptors and Their Adapter Molecules","volume":"75","author":"Tukhvatulin","year":"2010","journal-title":"Biochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/01.all.0000182537.55650.99","article-title":"Toll-like receptors and the eye","volume":"5","author":"Micera","year":"2005","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-540-72167-3_1","article-title":"Toll-Like receptors (TLRs) and their ligands","volume":"183","author":"Uematsu","year":"2008","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.trsl.2021.05.005","article-title":"Immune responses to injury and their links to eye disease","volume":"236","author":"Stepp","year":"2021","journal-title":"Transl. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3389\/fimmu.2018.00457","article-title":"The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker","volume":"9","author":"Hossain","year":"2018","journal-title":"Front Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/j.1365-2249.2009.03854.x","article-title":"Soluble forms of Toll-like receptor 4 are present in human saliva and modulate tumor necrosis factor-alpha secretion by macrophage-like cells","volume":"156","author":"Zunt","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.it.2010.01.002","article-title":"Crosstalk pathways between Toll-like receptors and the complement system","volume":"31","author":"Hajishengallis","year":"2010","journal-title":"Trends Immunol."},{"key":"ref_24","first-page":"2","article-title":"Toll-like receptor (TLR)-2\/4 expression in retinal ganglion cells in a high-glucose environment and its implications","volume":"25","author":"Zhao","year":"2016","journal-title":"Genet. Mol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ajo.2016.12.006","article-title":"Insights Into Epiretinal Membranes: Presence of Ectopic Inner Foveal Layers and a New Optical Coherence Tomography Staging Scheme","volume":"175","author":"Govetto","year":"2017","journal-title":"Am. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cacciamani, A., Cosimi, P., Ripandelli, G., Di Nicola, M., and Scarinci, F. (2021). Epiretinal Membrane Surgery: Structural Retinal Changes Correlate with the Improvement of Visual Function. J. Clin. Med., 10.","DOI":"10.3390\/jcm10010090"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zakeri, A., and Russo, M. (2018). Dual Role of Toll-like Receptors in Human and Experimental Asthma Models. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01027"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13045-014-0057-5","article-title":"Toll-like receptors in the pathogenesis of human B cell malignancies","volume":"7","author":"Liang","year":"2014","journal-title":"J. Hematol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1172\/JCI11837","article-title":"Toll-like receptor\u2013mediated NF-\u03baB activation: A phylogenetically conserved paradigm in innate immunity","volume":"107","author":"Zhang","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1590\/1806-9282.64.04.361","article-title":"Expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)\/Tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary diseases and their relationships with pulmonary vascular remodelling","volume":"64","author":"Yu","year":"2018","journal-title":"Rev. Assoc. Med. Bras."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/imr.12467","article-title":"More than complementing Tolls: Complement\u2013Toll-like receptor synergy and crosstalk in innate immunity and inflammation","volume":"274","author":"Hajishengallis","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mahaling, B., Low, S.W.Y., Beck, M., Kumar, D., Ahmed, S., Connor, T., Ahmad, B., and Chaurasia, S.S. (2022). Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052591"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s00109-021-02113-y","article-title":"The interplay of DAMPs, TLR4, and proinflammatory cytokines in pulmonary fibrosis","volume":"99","author":"Bolourani","year":"2021","journal-title":"J. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1167\/iovs.15-16504","article-title":"High-fat diet induces toll-like receptor 4-dependent macrophage\/microglial cell activation and retinal impairment","volume":"56","author":"Lee","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1016\/j.celrep.2020.01.064","article-title":"Toll-like Receptor 2 Facilitates Oxidative Damage-Induced Retinal Degeneration","volume":"30","author":"Mulfaul","year":"2020","journal-title":"Cell. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Klettner, A., and Roider, J. (2021). Retinal Pigment Epithelium Expressed Toll-like Receptors and Their Potential Role in Age-Related Macular Degeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168387"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"105960","DOI":"10.1016\/j.phrs.2021.105960","article-title":"Role of toll-like receptor 4 in diabetic retinopathy","volume":"175","author":"Bayan","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2972","DOI":"10.1093\/jac\/dkac254","article-title":"TLR2 and TLR4 activity in monocytes and macrophages after exposure to amoxicillin, ciprofloxacin, doxycycline and erythromycin","volume":"77","author":"Lagos","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s42269-019-0227-2","article-title":"Toll-like receptors activation, signaling, and targeting: An overview","volume":"43","author":"Sibaii","year":"2019","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.visres.2017.04.013","article-title":"Diabetic retinopathy and dysregulated innate immunity","volume":"139","author":"Xu","year":"2017","journal-title":"Vision Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1097\/IAE.0b013e3181ef8786","article-title":"Idiopathic and secondary epiretinal membranes: Do they differ in terms of morphology? An optical coherence tomography-based study","volume":"31","author":"Yazici","year":"2011","journal-title":"Retina"},{"key":"ref_42","first-page":"1794","article-title":"Cell proliferation in human epiretinal membranes: Characterization of cell types and correlation with disease condition and duration","volume":"17","author":"Oberstein","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1097\/IAE.0b013e31815ec275","article-title":"Human idiopathic epiretinal membranes express NGF and NGF receptors","volume":"28","author":"Minchiotti","year":"2008","journal-title":"Retina"},{"key":"ref_44","first-page":"1483","article-title":"Immunocytochemical identification of Muller\u2019s glia as a component of human epiretinal membranes","volume":"31","author":"Guerin","year":"1990","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"27739","DOI":"10.1038\/srep27739","article-title":"TLR2\/4 deficiency prevents oxygen-induced vascular degeneration and promotes revascularization by downregulating IL-17 in the retina","volume":"6","author":"He","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s10072-012-1236-1","article-title":"The expression of Toll-like receptors in murine M\u00fcller cells, the glial cells in retina","volume":"34","author":"Lin","year":"2013","journal-title":"Neurol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/glia.22296","article-title":"Microglia are required for astroglial Toll-like receptor 4 response and for optimal TLR2 and TLR3 response","volume":"60","author":"Holm","year":"2012","journal-title":"Glia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"671905","DOI":"10.1155\/2015\/671905","article-title":"Current Trends about Inner Limiting Membrane Peeling in Surgery for Epiretinal Membranes","volume":"2015","author":"Semeraro","year":"2015","journal-title":"J. Ophthalmol."},{"key":"ref_49","first-page":"1343","article-title":"The role of Toll-like receptors in retinal ischemic diseases","volume":"9","author":"Xu","year":"2016","journal-title":"Int. J. Ophthalmol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5824","DOI":"10.1167\/iovs.10-6357","article-title":"The role of TLR4 activation in photoreceptor mitochondrial oxidative stress","volume":"52","author":"Ko","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1128\/IAI.00149-12","article-title":"Toll-like receptor 2 ligand pretreatment attenuates retinal microglial inflammatory response but enhances phagocytic activity toward Staphylococcus aureus","volume":"80","author":"Kochan","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Kumar, A., and Shamsuddin, N. (2012). Retinal M\u00fcller glia initiate innate response to infectious stimuli via toll-like receptor signaling. PLoS ONE, 7.","DOI":"10.1371\/annotation\/951b4189-ee76-4a19-98f4-504f4355c45c"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1097\/IAE.0000000000000349","article-title":"Idiopathic Epiretinal Membrane","volume":"34","author":"Bu","year":"2014","journal-title":"Retina"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Owuraku, T.-L., Imran, M., and Winfried, M.A. (2022). Toll-Like Receptor Signalling Pathways and the Pathogenesis of Retinal Diseases. Front. Ophthalmol., 2.","DOI":"10.3389\/fopht.2022.850394"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1007\/s12031-020-01503-0","article-title":"Increased Neuroprotective Microglia and Photoreceptor Survival in the Retina from a Peptide Inhibitor of Myeloid Differentiation Factor 88 (MyD88)","volume":"70","author":"Garces","year":"2020","journal-title":"J. Mol. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7128","DOI":"10.4049\/jimmunol.166.12.7128","article-title":"An essential role of the NF-kappa B\/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells","volume":"166","author":"Li","year":"2001","journal-title":"J Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Szczepan, M., Llori\u00e1n-Salvador, M., Chen, M., and Xu, H. (2022). Immune Cells in Subretinal Wound Healing and Fibrosis. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.916719"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.4049\/jimmunol.1300591","article-title":"Coexpression of TLR2 or TLR4 with HLA-DR potentiates the superantigenic activities of Mycoplasma arthritidis-derived mitogen","volume":"192","author":"Shio","year":"2014","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Balogh, A., Milib\u00e1k, T., Szab\u00f3, V., Nagy, Z.Z., Kaarniranta, K., and Resch, M.D. (2020). Immunological biomarkers of the vitreous responsible for proliferative alteration in the different forms of retinal detachment. BMC Ophthalmol., 20.","DOI":"10.1186\/s12886-020-01745-x"},{"key":"ref_60","first-page":"5338","article-title":"Eotaxin-2 increased toll-like receptor 4 expression in endothelial cells in vitro and exacerbates high-cholesterol diet-induced atherogenesis in vivo","volume":"8","author":"Tsai","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1007\/s00417-015-3127-7","article-title":"Elevated vitreous body glial fibrillary acidic protein in retinal diseases","volume":"253","author":"Rejdak","year":"2015","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.1038\/s41598-017-04199-2","article-title":"Microbial Antigens Stimulate Metalloprotease-7 Secretion in Human B-Lymphocytes Using mTOR-Dependent and Independent Pathways","volume":"7","author":"Ali","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.archoralbio.2012.12.009","article-title":"Toll-like receptor activation and mechanical force stimulation promote the secretion of matrix metalloproteinases 1, 3 and 10 of human periodontal fibroblasts via p38, JNK and NF-kB","volume":"58","author":"Lisboa","year":"2013","journal-title":"Arch. Oral Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/08830185.2019.1609962","article-title":"The complement system, toll-like receptors and inflammasomes in host defense: Three musketeers\u2019 one target","volume":"38","author":"Kumar","year":"2019","journal-title":"Int. Rev. Immunol."},{"key":"ref_65","first-page":"1195","article-title":"Anaphylatoxin levels in human vitreous humor","volume":"29","author":"Mondino","year":"1988","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","first-page":"1288","article-title":"Anaphylatoxin levels in human aqueous humor","volume":"8","author":"Mondino","year":"1986","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","first-page":"871","article-title":"Activated complement in inflamed aqueous humor","volume":"25","author":"Mondino","year":"1984","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/eye.2011.109","article-title":"Sub-lytic C5b-9 induces functional changes in retinal pigment epithelial cells consistent with age-related macular degeneration","volume":"25","author":"Lueck","year":"2011","journal-title":"Eye"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/cr.2009.139","article-title":"Complement and its role in innate and adaptive immune responses","volume":"20","author":"Dunkelberger","year":"2010","journal-title":"Cell Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.jacbts.2020.03.015","article-title":"Innate Immune Receptors, Key Actors in Cardiovascular Diseases","volume":"5","author":"Prieto","year":"2020","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wenger, M., Grosse-Kathoefer, S., Kraiem, A., Pelamatti, E., Nunes, N., Pointner, L., and Aglas, L. (2023). When the allergy alarm bells toll: The role of Toll-like receptors in allergic diseases and treatment. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1204025"},{"key":"ref_72","first-page":"1272118","article-title":"Sex and gender affect immune aging","volume":"28","author":"Accardi","year":"2023","journal-title":"Front Aging."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e63425","DOI":"10.7554\/eLife.63425","article-title":"Sex differences in biological aging with a focus on human studies","volume":"10","year":"2021","journal-title":"eLife"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e014644","DOI":"10.1136\/bmjopen-2016-014644","article-title":"Prevalence and risk factors of epiretinal membranes: A systematic review and meta-analysis of population-based studies","volume":"7","author":"Xiao","year":"2017","journal-title":"BMJ Open"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.intimp.2018.03.002","article-title":"Toll-like receptors in immunity and inflammatory diseases: Past, present, and future","volume":"59","author":"Kumar","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"E36","DOI":"10.1093\/nar\/30.9.e36","article-title":"Relative Expression Software Tool (REST\u00a9) for group wise comparison and statistical analysis of relative expression results in real-time PCR","volume":"30","author":"Pfaffl","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41577-019-0215-7","article-title":"DAMP-sensing receptors in sterile inflammation and inflammatory diseases","volume":"20","author":"Gong","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2174\/1389203711314010006","article-title":"Toll-like receptors: Sensor molecules for detecting damage to the nervous system","volume":"14","author":"Lee","year":"2013","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1189\/jlb.3VMR0316-132R","article-title":"Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases-C3 or C5 emerge together with CD14 as promising targets","volume":"101","author":"Pischke","year":"2017","journal-title":"J. Leukoc. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/14\/7732\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:16:58Z","timestamp":1760109418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/14\/7732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,15]]},"references-count":79,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25147732"],"URL":"https:\/\/doi.org\/10.3390\/ijms25147732","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,15]]}}}