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Importantly, PRPE-SF treatment preserved retinal structure and scotopic b-wave amplitudes, suggesting therapeutic potential for delaying retinal degeneration. PRPE-SF is uniquely produced using biomimetic membranes for RPE polarization and maturation, promoting a protective RPE secretome phenotype. Additionally, PRPE-SF is produced without animal serum to avoid immunogenicity in future clinical development. Lastly, PRPE-SF is a combination of neurotrophic factors, potentially ameliorating multiple dysfunctions in retinal degenerations. In conclusion, PRPE-SF offers a promising therapeutic candidate for retinal degenerative diseases, advancing the development of effective therapeutic strategies for these debilitating conditions.<\/jats:p>","DOI":"10.3390\/cells12131689","type":"journal-article","created":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T01:54:56Z","timestamp":1687485296000},"page":"1689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Polarized RPE Secretome Preserves Photoreceptors in Retinal Dystrophic RCS Rats"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0951-6647","authenticated-orcid":false,"given":"Kabir","family":"Ahluwalia","sequence":"first","affiliation":[{"name":"Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, 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USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.exer.2010.08.022","article-title":"Trophic factors GDNF and BDNF improve function of retinal sheet transplants","volume":"91","author":"Yang","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.survophthal.2013.09.004","article-title":"Trophic factors in the pathogenesis and therapy for retinal degenerative diseases","volume":"59","author":"Kolomeyer","year":"2014","journal-title":"Surv. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1080\/08820538.2021.1890793","article-title":"Nerve Growth Factor as an Ocular Therapy: Applications, Challenges, and Future Directions","volume":"36","author":"Kanu","year":"2021","journal-title":"Semin. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1167\/iovs.12-11239","article-title":"Subretinal Implantation of Retinal Pigment Epithelial Cells Derived From Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer","volume":"54","author":"Diniz","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0006-8993(92)91015-7","article-title":"Effects of RPE-cell factors secreted from permselective fibers on retinal cells in vitro","volume":"587","author":"Sheedlo","year":"1992","journal-title":"Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1006\/exer.1993.1183","article-title":"Effects of RPE age and culture conditions on support of photoreceptor cell survival in transplanted RCS dystrophic rats","volume":"57","author":"Sheedlo","year":"1993","journal-title":"Exp. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/BF02634278","article-title":"Retinal pigment epithelial cell support of photoreceptor survival in vitro","volume":"31","author":"Sheedlo","year":"1995","journal-title":"Vitr. Cell. Dev. Biol.-Anim. J. Soc. Vitr. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0165-3806(96)00008-9","article-title":"Influence of a retinal pigment epithelial cell factor(s) on rat retinal progenitor cells","volume":"93","author":"Sheedlo","year":"1996","journal-title":"Dev. Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/(SICI)1097-4547(19960615)44:6<519::AID-JNR2>3.0.CO;2-E","article-title":"Effects of retinal pigment epithelial cell-secreted factors on neonatal rat retinal explant progenitor cells","volume":"44","author":"Sheedlo","year":"1996","journal-title":"J. Neurosci. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1076\/ceyr.16.2.116.5091","article-title":"A transformed neonatal rat retinal pigment epithelial cell line: Secreted protein analysis and fibroblast growth factor and receptor expression","volume":"16","author":"Sheedlo","year":"1997","journal-title":"Curr. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0165-3806(97)00219-8","article-title":"RPE secreted proteins and antibody influence photoreceptor cell survival and maturation","volume":"107","author":"Sheedlo","year":"1998","journal-title":"Dev. Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1073\/pnas.1814014116","article-title":"Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation in mice","volume":"116","author":"Landowski","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"591067","DOI":"10.3389\/fcell.2020.591067","article-title":"Not All Stressors Are Equal: Mechanism of Stressors on RPE Cell Degeneration","volume":"8","author":"Tong","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12694","DOI":"10.1038\/s41598-022-16701-6","article-title":"Oxidative stress differentially impacts apical and basolateral secretion of angiogenic factors from human iPSC-derived retinal pigment epithelium cells","volume":"12","author":"Chen","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1111\/jcmm.12834","article-title":"Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells","volume":"20","author":"Barcia","year":"2016","journal-title":"J. Cell Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sreekumar, P.G., Kannan, R., Kitamura, M., Spee, C., Barron, E., Ryan, S.J., and Hinton, D.R. (2010). \u03b1B Crystallin Is Apically Secreted within Exosomes by Polarized Human Retinal Pigment Epithelium and Provides Neuroprotection to Adjacent Cells. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012578"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"51","DOI":"10.18632\/aging.100516","article-title":"Chronic oxidative stress upregulates Drusen-related protein expression in adult human RPE stem cell-derived RPE cells: A novel culture model for dry AMD","volume":"5","author":"Rabin","year":"2012","journal-title":"Aging"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.5966\/sctm.2014-0179","article-title":"Defined culture of human embryonic stem cells and xeno-free derivation of retinal pigmented epithelial cells on a novel, synthetic substrate","volume":"4","author":"Pennington","year":"2015","journal-title":"Stem Cells Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000338749","article-title":"A novel approach for subretinal implantation of ultrathin substrates containing stem cell-derived retinal pigment epithelium monolayer","volume":"48","author":"Hu","year":"2012","journal-title":"Ophthalmic. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1002\/term.1458","article-title":"Differentiation of human pluripotent stem cells to retinal pigmented epithelium in defined conditions using purified extracellular matrix proteins","volume":"7","author":"Rowland","year":"2013","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s10544-012-9645-8","article-title":"Mesh-supported submicron parylene-C membranes for culturing retinal pigment epithelial cells","volume":"14","author":"Lu","year":"2012","journal-title":"Biomed Microdevices"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1007\/s00417-018-4134-2","article-title":"A new immunodeficient retinal dystrophic rat model for transplantation studies using human-derived cells","volume":"256","author":"Thomas","year":"2018","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1038\/srep03963","article-title":"Hes1 is involved in the self-renewal and tumourigenicity of stem-like cancer cells in colon cancer","volume":"4","author":"Gao","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_47","first-page":"1470","article-title":"The retinal determination gene Dachshund restricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex","volume":"142","author":"Casares","year":"2015","journal-title":"Development"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.ydbio.2008.12.022","article-title":"The LIM homeobox transcription factor Lhx2 is required to specify the retina field and synergistically cooperates with Pax6 for Six6 trans-activation","volume":"327","author":"Tetreault","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1242\/dev.041202","article-title":"Lhx2 links the intrinsic and extrinsic factors that control optic cup formation","volume":"136","author":"Yun","year":"2009","journal-title":"Development"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"38","DOI":"10.5115\/acb.2012.45.1.38","article-title":"Nestin expressing progenitor cells during establishment of the neural retina and its vasculature","volume":"45","author":"Lee","year":"2012","journal-title":"Anat. Cell Biol."},{"key":"ref_51","first-page":"5","article-title":"Spatiotemporal pattern of doublecortin expression in the retina of the sea lamprey","volume":"10","year":"2016","journal-title":"Front. Neuroanat."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7028","DOI":"10.1523\/JNEUROSCI.1624-07.2007","article-title":"Late-stage neuronal progenitors in the retina are radial Muller glia that function as retinal stem cells","volume":"27","author":"Bernardos","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lamba, D.A., McUsic, A., Hirata, R.K., Wang, P.R., Russell, D., and Reh, T.A. (2010). Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008763"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.1167\/iovs.04-0511","article-title":"Multipotent retinal progenitors express developmental markers, differentiate into retinal neurons, and preserve light-mediated behavior","volume":"45","author":"Klassen","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1167\/iovs.08-3067","article-title":"Molecular characterization of human retinal progenitor cells","volume":"50","author":"Schmitt","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13898","DOI":"10.1074\/jbc.M209164200","article-title":"Nerve Growth Factor Protects against 6-Hydroxydopamine-induced Oxidative Stress by Increasing Expression of Heme Oxygenase-1 in a Phosphatidylinositol 3-Kinase-dependent Manner*","volume":"278","author":"Salinas","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_57","first-page":"388","article-title":"Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model","volume":"19","author":"Hacioglu","year":"2016","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"152","DOI":"10.21037\/atm-20-8040","article-title":"Leukemia inhibitory factor protects photoreceptor cone cells against oxidative damage through activating JAK\/STAT3 signaling","volume":"9","author":"Dong","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1042\/CS20130463","article-title":"PEDF and its roles in physiological and pathological conditions: Implication in diabetic and hypoxia-induced angiogenic diseases","volume":"128","author":"He","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9517","DOI":"10.1038\/s41598-017-09743-8","article-title":"Retinal cell death dependent reactive proliferative gliosis in the mouse retina","volume":"7","author":"Oertel","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hollingsworth, T.J., and Gross, A.K. (2020). Innate and Autoimmunity in the Pathogenesis of Inherited Retinal Dystrophy. Cells, 9.","DOI":"10.3390\/cells9030630"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3389\/fimmu.2012.00360","article-title":"Activation of PAD4 in NET formation","volume":"3","author":"Rohrbach","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1167\/iovs.10-6413","article-title":"Polarized Secretion of PEDF from Human Embryonic Stem Cell\u2013Derived RPE Promotes Retinal Progenitor Cell Survival","volume":"52","author":"Zhu","year":"2011","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_64","first-page":"216","article-title":"Retinal Pigment Epithelial Cell Conditioned Medium Enhances the Yield of RPE Cells Differentiated from Human Embryonic Stem Cells","volume":"5","year":"2015","journal-title":"J. Clin. Exp. Pathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/0014-4835(92)90020-S","article-title":"RPE conditioned medium stimulates photoreceptor cell survival, neurite outgrowth and differentiation in vitro","volume":"54","author":"Gaur","year":"1992","journal-title":"Exp. Eye Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1007\/s12177-011-9076-4","article-title":"RPE-secreted factors: Influence differentiation in human retinal cell line in dose- and density-dependent manner","volume":"3","author":"Dutt","year":"2010","journal-title":"J. Ocul. Biol. Dis. Infor."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Kimura, A., Namekata, K., Guo, X., Harada, C., and Harada, T. (2016). Neuroprotection, Growth Factors and BDNF-TrkB Signalling in Retinal Degeneration. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091584"},{"key":"ref_68","unstructured":"Raffaele, O.S., and Domp\u00e9 Farmaceutici, S.p.A. (2023, March 06). Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02609165."},{"key":"ref_69","unstructured":"GenVec (2023, March 06). Study of AdGVPEDF.11D in Neovascular Age-related Macular Degeneration (AMD), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT00109499."},{"key":"ref_70","unstructured":"Domp\u00e9 Farmaceutici, S.p.A., and Cromsource (2023, March 06). Study to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution Versus Vehicle in Patients With Glaucoma, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02855450."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.freeradbiomed.2016.02.027","article-title":"Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration","volume":"94","author":"Ye","year":"2016","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ai.2016.02.001","article-title":"Malondialdehyde Epitopes as Targets of Immunity and the Implications for Atherosclerosis","volume":"131","author":"Busch","year":"2016","journal-title":"Adv. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.exer.2013.03.017","article-title":"Retinal deimination and PAD2 levels in retinas from donors with age-related macular degeneration (AMD)","volume":"111","author":"Bonilha","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_74","first-page":"289360","article-title":"Neutrophils compromise retinal pigment epithelial barrier integrity","volume":"2010","author":"Hinton","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"eaay5356","DOI":"10.1126\/science.aay5356","article-title":"Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy","volume":"369","author":"Binet","year":"2020","journal-title":"Science"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1158\/1535-7163.MCT-21-0414","article-title":"NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment","volume":"20","author":"Dong","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e2121875119","DOI":"10.1073\/pnas.2121875119","article-title":"Compartmentalized citrullination in Muller glial endfeet during retinal degeneration","volume":"119","author":"Palko","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/hmg\/9.4.645","article-title":"Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat","volume":"9","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/s12967-019-1976-2","article-title":"Animal to human translation: A systematic scoping review of reported concordance rates","volume":"17","author":"Leenaars","year":"2019","journal-title":"J. Transl. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/13\/1689\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:58:35Z","timestamp":1760126315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/13\/1689"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,22]]},"references-count":79,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["cells12131689"],"URL":"https:\/\/doi.org\/10.3390\/cells12131689","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,22]]}}}