{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:30:52Z","timestamp":1790922652378,"version":"4.1.0"},"reference-count":133,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82471106"],"award-info":[{"award-number":["82471106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Tianjin Key Medical Discipline Construction Project","award":["TJYXZDXK-3-004A-2"],"award-info":[{"award-number":["TJYXZDXK-3-004A-2"]}]},{"name":"Tianjin Health Commission Key Discipline Special Project","award":["TJWJ2023XK009"],"award-info":[{"award-number":["TJWJ2023XK009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>11-cis-retinal, the indispensable chromophore of photoreceptor opsins, is fundamental for light detection and the initiation of visual signal transduction. Its synthesis and regeneration through the visual cycle are critical not only for phototransduction but also for maintaining retinal homeostasis. Disruption of key enzymes, such as retinal pigment epithelium (RPE)65 and retinol dehydrogenases, results in toxic retinoid accumulation, oxidative stress, and progressive photoreceptor degeneration. These pathological mechanisms contribute to inherited and acquired retinal diseases, including Stargardt disease type 1, age-related macular degeneration, Leber congenital amaurosis, retinitis pigmentosa, and fundus albipunctatus. Recent therapeutic advances, ranging from gene replacement therapy with RPE65 (voretigene neparvovec, Luxturna\u00ae) to small-molecule modulators and antioxidant strategies, underscore the translational potential of targeting chromophore metabolism. This review outlines molecular processes underlying chromophore synthesis and regeneration, elucidates how disruptions in these processes contribute to inherited and acquired retinal pathologies, and evaluates existing and emerging therapeutic strategies that target chromophore metabolism. We highlight ongoing challenges and critical knowledge gaps to guide future investigations on basic science, translational research, and clinical practice. This review provides a comprehensive overview of the molecular mechanisms, current therapeutic approaches, and outstanding challenges, with a focus on future intervention directions.<\/jats:p>","DOI":"10.3390\/biom15121676","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T08:49:22Z","timestamp":1764665362000},"page":"1676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mechanisms and Functions of Chromophore Regeneration in the Classical Visual Cycle: Implications for Retinal Disease Pathogenesis and Therapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Xinyue","family":"Yu","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Fan","sequence":"additional","affiliation":[{"name":"Tianjin Third Central Hospital, Tianjin 300384, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e489","DOI":"10.1016\/S2214-109X(20)30488-5","article-title":"The Lancet Global Health Commission on Global Eye Health: Vision beyond 2020","volume":"9","author":"Burton","year":"2021","journal-title":"Lancet Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.preteyeres.2010.11.001","article-title":"The cone-specific visual cycle","volume":"30","author":"Wang","year":"2011","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev-vision-100820-083937","article-title":"The Retina-Based Visual Cycle","volume":"10","author":"Sato","year":"2024","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3483","DOI":"10.1167\/iovs.10-6694","article-title":"Rod outer segment retinol formation is independent of Abca4, arrestin, rhodopsin kinase, and rhodopsin palmitylation","volume":"52","author":"Blakeley","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ajo.2023.06.013","article-title":"One-Year Outcomes of Oral Treatment With Alga Capsules Containing Low Levels of 9-cis-\u03b2-Carotene in RDH5-Related Fundus Albipunctatus","volume":"254","author":"Mizobuchi","year":"2023","journal-title":"Am. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100861","DOI":"10.1016\/j.preteyeres.2020.100861","article-title":"Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations","volume":"79","author":"Cremers","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101244","DOI":"10.1016\/j.preteyeres.2024.101244","article-title":"Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes","volume":"100","author":"Georgiou","year":"2024","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yang, G., Liu, Z., Xie, S., Li, C., Lv, L., Zhang, M., and Zhao, J. (2017). Genetic and phenotypic characteristics of four Chinese families with fundus albipunctatus. Sci. Rep., 7.","DOI":"10.1038\/srep46285"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101110","DOI":"10.1016\/j.preteyeres.2022.101110","article-title":"RNA-targeting strategies as a platform for ocular gene therapy","volume":"92","author":"Kumar","year":"2023","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.1016\/j.ymthe.2024.10.017","article-title":"Recombinant adeno-associated virus as a delivery platform for ocular gene therapy: A comprehensive review","volume":"32","author":"Wang","year":"2024","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, Y., Ma, X., Muthuraman, P., Raja, A., Jayaraman, A., Petrukhin, K., Cioffi, C.L., Ma, J.X., and Moiseyev, G. (2022). The novel visual cycle inhibitor (\u00b1)-RPE65-61 protects retinal photoreceptors from light-induced degeneration. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0269437"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/s41589-024-01554-z","article-title":"Carotenoid cleavage enzymes evolved convergently to generate the visual chromophore","volume":"20","author":"Solano","year":"2024","journal-title":"Nat. Chem. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"108776","DOI":"10.1016\/j.exer.2021.108776","article-title":"Intraperitoneal chromophore injections delay early-onset and rapid retinal cone degeneration in a mouse model of Leber congenital amaurosis","volume":"212","author":"Dai","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1089\/hum.2022.240","article-title":"Gene Supplementation in Mice Heterozygous for the D477G RPE65 Variant Implicated in Autosomal Dominant Retinitis Pigmentosa","volume":"34","author":"Feathers","year":"2023","journal-title":"Hum. Gene Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4714","DOI":"10.1523\/JNEUROSCI.3722-10.2011","article-title":"Interphotoreceptor retinoid-binding protein as the physiologically relevant carrier of 11-cis-retinol in the cone visual cycle","volume":"31","author":"Parker","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"19137","DOI":"10.1074\/jbc.RA119.011169","article-title":"Photic generation of 11-cis-retinal in bovine retinal pigment epithelium","volume":"294","author":"Zhang","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101360","DOI":"10.1016\/j.preteyeres.2025.101360","article-title":"Advances and therapeutic opportunities in visual cycle modulation","volume":"106","author":"Zaluski","year":"2025","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2418031121","DOI":"10.1073\/pnas.2418031121","article-title":"Dark continuous noise from visual pigment as a major mechanism underlying rod-cone difference in light sensitivity","volume":"121","author":"Chai","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5693","DOI":"10.1021\/ja907756e","article-title":"Protein fluctuations as the possible origin of the thermal activation of rod photoreceptors in the dark","volume":"132","author":"Furutani","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"24662","DOI":"10.1074\/jbc.M112.354514","article-title":"Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12","volume":"287","author":"Chen","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5435","DOI":"10.1167\/iovs.09-3944","article-title":"Limited roles of Rdh8, Rdh12, and Abca4 in all-trans-retinal clearance in mouse retina","volume":"50","author":"Maeda","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19565","DOI":"10.1073\/pnas.0707477104","article-title":"Redundant and unique roles of retinol dehydrogenases in the mouse retina","volume":"104","author":"Maeda","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E11120","DOI":"10.1073\/pnas.1802519115","article-title":"Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration","volume":"115","author":"Lenis","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sarkar, H., Toms, M., and Moosajee, M. (2021). Involvement of Oxidative and Endoplasmic Reticulum Stress in RDH12-Related Retinopathies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168863"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7302","DOI":"10.1073\/pnas.1319142111","article-title":"Identification of the 11-cis-specific retinyl-ester synthase in retinal M\u00fcller cells as multifunctional O-acyltransferase (MFAT)","volume":"111","author":"Kaylor","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10426","DOI":"10.1073\/pnas.0600917103","article-title":"Inner retinal photoreception independent of the visual retinoid cycle","volume":"103","author":"Tu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101013","DOI":"10.1016\/j.preteyeres.2021.101013","article-title":"Retinal pigment epithelium 65 kDa protein (RPE65): An update","volume":"88","author":"Kiser","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6835","DOI":"10.1167\/iovs.09-3870","article-title":"Remaining rod activity mediates visual behavior in adult Rpe65\u2212\/\u2212 mice","volume":"51","author":"Cachafeiro","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27239","DOI":"10.1074\/jbc.M115.682096","article-title":"Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice","volume":"290","author":"Sahu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.exer.2010.08.013","article-title":"Retinol dehydrogenases (RDHs) in the visual cycle","volume":"91","author":"Parker","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6753","DOI":"10.1113\/JP272831","article-title":"cis Retinol oxidation regulates photoreceptor access to the retina visual cycle and cone pigment regeneration","volume":"594","author":"Sato","year":"2016","journal-title":"J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1167\/iovs.07-1664","article-title":"Carrier of R14W in carbonic anhydrase IV presents Bothnia dystrophy phenotype caused by two allelic mutations in RLBP1","volume":"49","author":"Burstedt","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ozawa, Y. (2020). Oxidative stress in the light-exposed retina and its implication in age-related macular degeneration. Redox Biol., 37.","DOI":"10.1016\/j.redox.2020.101779"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1042\/BCJ20180193","article-title":"Structural biology of 11-cis-retinaldehyde production in the classical visual cycle","volume":"475","author":"Daruwalla","year":"2018","journal-title":"Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.freeradbiomed.2022.12.008","article-title":"Induction of ferroptosis by HO-1 contributes to retinal degeneration in mice with defective clearance of all-trans-retinal","volume":"194","author":"Chen","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ward, R., Sundaramurthi, H., Di Giacomo, V., and Kennedy, B.N. (2018). Enhancing Understanding of the Visual Cycle by Applying CRISPR\/Cas9 Gene Editing in Zebrafish. Front. Cell Dev. Biol., 6.","DOI":"10.3389\/fcell.2018.00037"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100055","DOI":"10.1016\/j.jlr.2021.100055","article-title":"LRAT coordinates the negative-feedback regulation of intestinal retinoid biosynthesis from \u03b2-carotene","volume":"62","author":"Ramkumar","year":"2021","journal-title":"J. Lipid Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yang, B., Yang, K., Xi, R., Chen, J., and Wu, Y. (2024). Quercetin Alleviates All-Trans-Retinal-Induced Photoreceptor Apoptosis and Retinal Degeneration by Inhibiting the ER Stress-Related PERK Signaling. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413624"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"He, D., Tao, L., Cai, B., Chen, X., Wang, Y., Li, S., Liao, C., Chen, Y., Chen, J., and Liu, Z. (2023). eIF2\u03b1 incites photoreceptor cell and retina damage by all-trans-retinal. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2023.104686"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Abdolrahimzadeh, S., Formisano, M., Di Pippo, M., Lodesani, M., and Lotery, A.J. (2022). The Role of the Choroid in Stargardt Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147607"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yang, B., Yang, K., Chen, Y., Li, Q., Chen, J., Li, S., and Wu, Y. (2025). Exposure of A2E to blue light promotes ferroptosis in the retinal pigment epithelium. Cell. Mol. Biol. Lett., 30.","DOI":"10.1186\/s11658-025-00700-2"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/s41419-017-0200-7","article-title":"Photosensitization of A2E triggers telomere dysfunction and accelerates retinal pigment epithelium senescence","volume":"9","author":"Wang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Sajovic, J., Megli\u010d, A., Glava\u010d, D., Markelj, \u0160., Hawlina, M., and Fakin, A. (2022). The Role of Vitamin A in Retinal Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031014"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.tox.2016.10.005","article-title":"All-trans-retinal dimer formation alleviates the cytotoxicity of all-trans-retinal in human retinal pigment epithelial cells","volume":"371","author":"Li","year":"2016","journal-title":"Toxicology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"101036","DOI":"10.1016\/j.preteyeres.2021.101036","article-title":"Structure and function of ABCA4 and its role in the visual cycle and Stargardt macular degeneration","volume":"89","author":"Molday","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1167\/iovs.62.2.1","article-title":"Relative Contributions of All-Trans and 11-Cis Retinal to Formation of Lipofuscin and A2E Accumulating in Mouse Retinal Pigment Epithelium","volume":"62","author":"Boyer","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"18822","DOI":"10.1074\/jbc.M501757200","article-title":"Role of photoreceptor-specific retinol dehydrogenase in the retinoid cycle in vivo","volume":"280","author":"Maeda","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5602","DOI":"10.1167\/iovs.13-11688","article-title":"Fundus autofluorescence in the Abca4(\u2212\/\u2212) mouse model of Stargardt disease--correlation with accumulation of A2E, retinal function, and histology","volume":"54","author":"Barnard","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Cai, B., Liao, C., He, D., Chen, J., Han, J., Lu, J., Qin, K., Liang, W., Wu, X., and Liu, Z. (2022). Gasdermin E mediates photoreceptor damage by all-trans-retinal in the mouse retina. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2021.101553"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1167\/iovs.15-18993","article-title":"Acute Stress Responses Are Early Molecular Events of Retinal Degeneration in Abca4-\/-Rdh8-\/- Mice After Light Exposure","volume":"57","author":"Parmar","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1016\/j.bbadis.2018.04.014","article-title":"A novel RPE65 inhibitor CU239 suppresses visual cycle and prevents retinal degeneration","volume":"1864","author":"Shin","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1172\/JCI80950","article-title":"Molecular pharmacodynamics of emixustat in protection against retinal degeneration","volume":"125","author":"Zhang","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8287","DOI":"10.1021\/acs.jmedchem.1c00279","article-title":"Rational Alteration of Pharmacokinetics of Chiral Fluorinated and Deuterated Derivatives of Emixustat for Retinal Therapy","volume":"64","author":"Blum","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"32491","DOI":"10.1074\/jbc.M111.255877","article-title":"Alpha-phenyl-N-tert-butylnitrone (PBN) prevents light-induced degeneration of the retina by inhibiting RPE65 protein isomerohydrolase activity","volume":"286","author":"Mandal","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Piotter, E., McClements, M.E., and MacLaren, R.E. (2021). Therapy Approaches for Stargardt Disease. Biomolecules, 11.","DOI":"10.3390\/biom11081179"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ghenciu, L.A., Ha\u021began, O.A., Stoicescu, E.R., Iacob, R., and \u0218i\u0219u, A.M. (2024). Emerging Therapeutic Approaches and Genetic Insights in Stargardt Disease: A Comprehensive Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168859"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.preteyeres.2014.09.001","article-title":"Congenital stationary night blindness: An analysis and update of genotype-phenotype correlations and pathogenic mechanisms","volume":"45","author":"Zeitz","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ajo.2022.02.013","article-title":"Three-Year Safety Results of SAR422459 (EIAV-ABCA4) Gene Therapy in Patients With ABCA4-Associated Stargardt Disease: An Open-Label Dose-Escalation Phase I\/IIa Clinical Trial, Cohorts 1\u20135","volume":"240","author":"Parker","year":"2022","journal-title":"Am. J. Ophthalmol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40662-016-0063-5","article-title":"Epidemiology of age-related macular degeneration (AMD): Associations with cardiovascular disease phenotypes and lipid factors","volume":"3","author":"Pennington","year":"2016","journal-title":"Eye Vis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13094","DOI":"10.1073\/pnas.2000339117","article-title":"Altered photoreceptor metabolism in mouse causes late stage age-related macular degeneration-like pathologies","volume":"117","author":"Cheng","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6958","DOI":"10.1074\/jbc.RA120.013189","article-title":"Activation of JNK signaling promotes all-trans-retinal-induced photoreceptor apoptosis in mice","volume":"295","author":"Liao","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"108482","DOI":"10.1016\/j.pharmthera.2023.108482","article-title":"Retina and RPE lipid profile changes linked with ABCA4 associated Stargardt\u2019s maculopathy","volume":"249","author":"Farnoodian","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1167\/iovs.16-20734","article-title":"Aberrant Buildup of All-Trans-Retinal Dimer, a Nonpyridinium Bisretinoid Lipofuscin Fluorophore, Contributes to the Degeneration of the Retinal Pigment Epithelium","volume":"58","author":"Zhao","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41419-018-0331-5","article-title":"Light action spectrum on oxidative stress and mitochondrial damage in A2E-loaded retinal pigment epithelium cells","volume":"9","author":"Marie","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.freeradbiomed.2024.12.007","article-title":"Inhibition of JNK signaling attenuates photoreceptor ferroptosis caused by all-trans-retinal","volume":"227","author":"Yang","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Wang, W.Y., Bin, X., Xu, Y., Chen, S., Zhou, S., Chen, S., Cao, Y., Qiu, K., and Ng, T.K. (2025). The Profile of Retinal Ganglion Cell Death and Cellular Senescence in Mice with Aging. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125436"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"102142","DOI":"10.1016\/j.arr.2023.102142","article-title":"Ferroptosis in the ageing retina: A malevolent fire of diabetic retinopathy","volume":"93","author":"Li","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Fontaine, V., Monteiro, E., Brazhnikova, E., Lesage, L., Balducci, C., Guibout, L., Feraille, L., Elena, P.P., Sahel, J.A., and Veillet, S. (2016). Norbixin Protects Retinal Pigmented Epithelium Cells and Photoreceptors against A2E-Mediated Phototoxicity In Vitro and In Vivo. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167793"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6151","DOI":"10.18632\/aging.103014","article-title":"Systemic administration of the di-apocarotenoid norbixin (BIO201) is neuroprotective, preserves photoreceptor function and inhibits A2E and lipofuscin accumulation in animal models of age-related macular degeneration and Stargardt disease","volume":"12","author":"Fontaine","year":"2020","journal-title":"Aging"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Fontaine, V., Balducci, C., Dinan, L., Monteiro, E., Boumedine, T., Fourni\u00e9, M., Nguyen, V., Guibout, L., Clatot, J., and Latil, M. (2023). Anti-Inflammatory Effects and Photo- and Neuro-Protective Properties of BIO203, a New Amide Conjugate of Norbixin, in Development for the Treatment of Age-Related Macular Degeneration (AMD). Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065296"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1007\/s10787-025-01913-9","article-title":"Regulation of toll-like receptor signaling pathways in age-related eye disease: From mechanisms to targeted therapeutics","volume":"33","author":"Kong","year":"2025","journal-title":"Inflammopharmacology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s00011-013-0684-2","article-title":"Inflammaging: Should this term be suitable for age related macular degeneration too?","volume":"63","author":"Gallenga","year":"2014","journal-title":"Inflamm. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.tips.2023.08.012","article-title":"Beyond ferrostatin-1: A comprehensive review of ferroptosis inhibitors","volume":"44","author":"Scarpellini","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1186\/s12967-025-07195-7","article-title":"Ferrostatin-1, a ferroptosis inhibitor, mitigates all-trans-retinal-induced retinal pigment epithelium degeneration in mice","volume":"23","author":"Shen","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1007\/s40123-022-00640-6","article-title":"LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration","volume":"12","author":"Burton","year":"2023","journal-title":"Ophthalmol. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s40123-025-01119-w","article-title":"Is Multiwavelength Photobiomodulation Effective and Safe for Age-Related Macular Degeneration? A Systematic Review and Meta-Analysis","volume":"14","author":"Chen","year":"2025","journal-title":"Ophthalmol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1007\/s40123-024-01030-w","article-title":"Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration","volume":"13","author":"Borrelli","year":"2024","journal-title":"Ophthalmol. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Vingolo, E.M., Mascolo, S., Miccich\u00e8, F., and Manco, G. (2024). Retinitis Pigmentosa: From Pathomolecular Mechanisms to Therapeutic Strategies. Medicina, 60.","DOI":"10.3390\/medicina60010189"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Huang, C.H., Yang, C.M., Yang, C.H., Hou, Y.C., and Chen, T.C. (2021). Leber\u2019s Congenital Amaurosis: Current Concepts of Genotype-Phenotype Correlations. Genes, 12.","DOI":"10.3390\/genes12081261"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4210","DOI":"10.1021\/bi052382x","article-title":"Aberrant metabolites in mouse models of congenital blinding diseases: Formation and storage of retinyl esters","volume":"45","author":"Maeda","year":"2006","journal-title":"Biochemistry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"112091","DOI":"10.1016\/j.celrep.2023.112091","article-title":"PNPLA2 mobilizes retinyl esters from retinosomes and promotes the generation of 11-cis-retinal in the visual cycle","volume":"42","author":"Hara","year":"2023","journal-title":"Cell Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1021\/acs.biochem.6b00319","article-title":"Lecithin:Retinol Acyltransferase: A Key Enzyme Involved in the Retinoid (visual) Cycle","volume":"55","author":"Sears","year":"2016","journal-title":"Biochemistry"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"100855","DOI":"10.1016\/j.mcpro.2024.100855","article-title":"Retinal Proteome Profiling of Inherited Retinal Degeneration Across Three Different Mouse Models Suggests Common Drug Targets in Retinitis Pigmentosa","volume":"23","author":"Montaser","year":"2024","journal-title":"Mol. Cell. Proteom."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1016\/j.neuron.2019.04.004","article-title":"Light-Driven Regeneration of Cone Visual Pigments through a Mechanism Involving RGR Opsin in M\u00fcller Glial Cells","volume":"102","author":"Morshedian","year":"2019","journal-title":"Neuron"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"10422","DOI":"10.1074\/jbc.M312410200","article-title":"Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver","volume":"279","author":"Batten","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.3390\/nu5072646","article-title":"Vitamin A derivatives as treatment options for retinal degenerative diseases","volume":"5","author":"Perusek","year":"2013","journal-title":"Nutrients"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Chelstowska, S., Widjaja-Adhi, M.A., Silvaroli, J.A., and Golczak, M. (2016). Molecular Basis for Vitamin A Uptake and Storage in Vertebrates. Nutrients, 8.","DOI":"10.3390\/nu8110676"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bbalip.2011.03.005","article-title":"Key enzymes of the retinoid (visual) cycle in vertebrate retina","volume":"1821","author":"Kiser","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Kolesnikov, A.V., Tang, P.H., and Kefalov, V.J. (2018). Examining the Role of Cone-expressed RPE65 in Mouse Cone Function. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-32667-w"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e56840","DOI":"10.7554\/eLife.56840","article-title":"True S-cones are concentrated in the ventral mouse retina and wired for color detection in the upper visual field","volume":"9","author":"Kunze","year":"2020","journal-title":"eLife"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e2217885120","DOI":"10.1073\/pnas.2217885120","article-title":"Chromophore supply modulates cone function and survival in retinitis pigmentosa mouse models","volume":"120","author":"Xue","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"32114","DOI":"10.1073\/pnas.2012623117","article-title":"Inverse correlation between fatty acid transport protein 4 and vision in Leber congenital amaurosis associated with RPE65 mutation","volume":"117","author":"Li","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Aoun, M., Passerini, I., Chiurazzi, P., Karali, M., De Rienzo, I., Sartor, G., Murro, V., Filimonova, N., Seri, M., and Banfi, S. (2021). Inherited Retinal Diseases Due to RPE65 Variants: From Genetic Diagnostic Management to Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137207"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s12325-021-02036-7","article-title":"Epidemiology of Mutations in the 65-kDa Retinal Pigment Epithelium (RPE65) Gene-Mediated Inherited Retinal Dystrophies: A Systematic Literature Review","volume":"39","author":"Sallum","year":"2022","journal-title":"Adv. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Chiu, W., Lin, T.Y., Chang, Y.C., Isahwan-Ahmad Mulyadi Lai, H., Lin, S.C., Ma, C., Yarmishyn, A.A., Lin, S.C., Chang, K.J., and Chou, Y.B. (2021). An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094534"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/bmb\/ldy005","article-title":"Retinal gene therapy","volume":"126","author":"Kumaran","year":"2018","journal-title":"Br. Med. Bull."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(17)31868-8","article-title":"Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: A randomised, controlled, open-label, phase 3 trial","volume":"390","author":"Russell","year":"2017","journal-title":"Lancet"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.ophtha.2019.06.017","article-title":"Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation-Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials","volume":"126","author":"Maguire","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/j.ophtha.2021.03.031","article-title":"Durability of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease: Phase 3 Results at 3 and 4 Years","volume":"128","author":"Maguire","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1080\/14656566.2018.1448060","article-title":"Pharmacotherapy of retinal disease with visual cycle modulators","volume":"19","author":"Hussain","year":"2018","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1159\/000520895","article-title":"Genetic Analysis of Consanguineous Pakistani Families with Congenital Stationary Night Blindness","volume":"65","author":"Ansar","year":"2022","journal-title":"Ophthalmic Res."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Sahu, B., and Maeda, A. (2016). Retinol Dehydrogenases Regulate Vitamin A Metabolism for Visual Function. Nutrients, 8.","DOI":"10.3390\/nu8110746"},{"key":"ref_103","first-page":"1558","article-title":"Novel mutations in RDH5 cause fundus albipunctatus in two consanguineous Pakistani families","volume":"18","author":"Ajmal","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ajo.2024.06.016","article-title":"RDH5 and RLBP1-Associated Inherited Retinal Diseases: Refining the Spectrum of Stationary and Progressive Phenotypes","volume":"267","author":"Bianco","year":"2024","journal-title":"Am. J. Ophthalmol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"51482","DOI":"10.1074\/jbc.M409051200","article-title":"Elements in the N-terminal signaling sequence that determine cytosolic topology of short-chain dehydrogenases\/reductases. Studies with retinol dehydrogenase type 1 and cis-retinol\/androgen dehydrogenase type 1","volume":"279","author":"Zhang","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"6545","DOI":"10.1021\/acs.biochem.6b00907","article-title":"Structural Insights into the Drosophila melanogaster Retinol Dehydrogenase, a Member of the Short-Chain Dehydrogenase\/Reductase Family","volume":"55","author":"Hofmann","year":"2016","journal-title":"Biochemistry"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.exer.2005.06.015","article-title":"Focus on molecules: Cellular retinaldehyde-binding protein (CRALBP)","volume":"81","author":"Saari","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-94-024-0945-1_9","article-title":"Vitamin A and Vision","volume":"81","author":"Saari","year":"2016","journal-title":"Sub-Cell. Biochem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.1167\/iovs.09-3797","article-title":"The 11-cis-retinol dehydrogenase activity of RDH10 and its interaction with visual cycle proteins","volume":"50","author":"Farjo","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1172\/JCI79651","article-title":"CRALBP supports the mammalian retinal visual cycle and cone vision","volume":"125","author":"Xue","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1021\/ja411366w","article-title":"Human cellular retinaldehyde-binding protein has secondary thermal 9-cis-retinal isomerase activity","volume":"136","author":"Bolze","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_112","first-page":"844","article-title":"Release of 11-cis-retinal from cellular retinaldehyde-binding protein by acidic lipids","volume":"15","author":"Saari","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1146\/annurev.pharmtox.47.120505.105225","article-title":"Diseases caused by defects in the visual cycle: Retinoids as potential therapeutic agents","volume":"47","author":"Travis","year":"2007","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S0896-6273(01)00248-3","article-title":"Visual cycle impairment in cellular retinaldehyde binding protein (CRALBP) knockout mice results in delayed dark adaptation","volume":"29","author":"Saari","year":"2001","journal-title":"Neuron"},{"key":"ref_115","first-page":"100854","article-title":"CRISPR\/Cas9 systems: Delivery technologies and biomedical applications","volume":"18","author":"Du","year":"2023","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"15022","DOI":"10.1038\/mtm.2015.22","article-title":"AAV-mediated RLBP1 gene therapy improves the rate of dark adaptation in Rlbp1 knockout mice","volume":"2","author":"Choi","year":"2015","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"12397","DOI":"10.1074\/jbc.M207300200","article-title":"Disease-causing mutations in the cellular retinaldehyde binding protein tighten and abolish ligand interactions","volume":"278","author":"Golovleva","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1167\/iovs.06-0215","article-title":"Improvement in rod and cone function in mouse model of Fundus albipunctatus after pharmacologic treatment with 9-cis-retinal","volume":"47","author":"Maeda","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.oret.2019.02.008","article-title":"RPE65-Mutation Associated Fundus Albipunctatus with Cone Dystrophy","volume":"3","author":"Ramtohul","year":"2019","journal-title":"Ophthalmol. Retin."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"17638","DOI":"10.1021\/acs.jmedchem.5c01353","article-title":"Rationally Designed, Short-Acting RPE65 Inhibitors for Visual Cycle-Associated Retinopathies","volume":"68","author":"Bassetto","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Dayma, K., Rajanala, K., and Upadhyay, A. (2025). Stargardt\u2019s Disease: Molecular Pathogenesis and Current Therapeutic Landscape. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26147006"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.omtn.2023.05.008","article-title":"CRISPR-Cas9 in hiPSCs: A new era in personalized treatment for Stargardt disease","volume":"32","author":"Kuntam","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.preteyeres.2017.10.004","article-title":"Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives","volume":"63","author":"Dias","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"8140","DOI":"10.1021\/acs.jmedchem.3c00461","article-title":"Tuning the Metabolic Stability of Visual Cycle Modulators through Modification of an RPE65 Recognition Motif","volume":"66","author":"Bassetto","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Zaydon, Y.A., and Tsang, S.H. (2024). The ABCs of Stargardt disease: The latest advances in precision medicine. Cell Biosci., 14.","DOI":"10.1186\/s13578-024-01272-y"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"8415","DOI":"10.1073\/pnas.1506960112","article-title":"Rescue of the Stargardt phenotype in Abca4 knockout mice through inhibition of vitamin A dimerization","volume":"112","author":"Barnard","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Wang, L., Shah, S.M., Mangwani-Mordani, S., and Gregori, N.Z. (2023). Updates on Emerging Interventions for Autosomal Recessive ABCA4-Associated Stargardt Disease. J. Clin. Med., 12.","DOI":"10.3390\/jcm12196229"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"5863","DOI":"10.1021\/acs.jmedchem.5b00423","article-title":"Bicyclic [3.3.0]-Octahydrocyclopenta[c]pyrrolo Antagonists of Retinol Binding Protein 4: Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease","volume":"58","author":"Cioffi","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"11574","DOI":"10.1074\/jbc.RA118.002062","article-title":"A non-retinoid antagonist of retinol-binding protein 4 rescues phenotype in a model of Stargardt disease without inhibiting the visual cycle","volume":"293","author":"Racz","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1182\/blood.2023022589","article-title":"Vector integration and fate in the hemophilia dog liver multiple years after AAV-FVIII gene transfer","volume":"143","author":"Batty","year":"2024","journal-title":"Blood"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1007\/s40123-023-00812-y","article-title":"Shedding Light on Photobiomodulation Therapy for Age-Related Macular Degeneration: A Narrative Review","volume":"12","author":"Fantaguzzi","year":"2023","journal-title":"Ophthalmol. Ther."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"4714","DOI":"10.1016\/j.ymthe.2025.06.045","article-title":"Peeling back the layers of immunogenicity in Cas9-based genomic medicine","volume":"33","author":"Stigzelius","year":"2025","journal-title":"Mol. Ther."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"100770","DOI":"10.1016\/j.xops.2025.100770","article-title":"Transplant of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Strips for Macular Degeneration and Retinitis Pigmentosa","volume":"5","author":"Sakai","year":"2025","journal-title":"Ophthalmol. 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