{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:42:53Z","timestamp":1792190573771,"version":"4.4.0"},"reference-count":81,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Stargardt disease, one of the most common forms of inherited retinal diseases, affects individuals worldwide. The primary cause is mutations in the ABCA4 gene, leading to the accumulation of toxic byproducts in the retinal pigment epithelium (RPE) and subsequent photoreceptor cell degeneration. Over the past few years, research on Stargardt disease has advanced significantly, focusing on clinical and molecular genetics. Recent studies have explored various innovative therapeutic approaches, including gene therapy, stem cell therapy, and pharmacological interventions. Gene therapy has shown promise, particularly with adeno-associated viral (AAV) vectors capable of delivering the ABCA4 gene to retinal cells. However, challenges remain due to the gene\u2019s large size. Stem cell therapy aims to replace degenerated RPE and photoreceptor cells, with several clinical trials demonstrating safety and preliminary efficacy. Pharmacological approaches focus on reducing toxic byproduct accumulation and modulating the visual cycle. Precision medicine, targeting specific genetic mutations and pathways, is becoming increasingly important. Novel techniques such as clustered regularly interspaced palindromic repeats (CRISPR)\/Cas9 offer potential for directly correcting genetic defects. This review aims to synthesize recent advancements in understanding and treating Stargardt disease. By highlighting breakthroughs in genetic therapies, stem cell treatments, and novel pharmacological strategies, it provides a comprehensive overview of emerging therapeutic options.<\/jats:p>","DOI":"10.3390\/ijms25168859","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T10:28:41Z","timestamp":1723631321000},"page":"8859","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Emerging Therapeutic Approaches and Genetic Insights in Stargardt Disease: A Comprehensive Review"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5326-5438","authenticated-orcid":false,"given":"Laura Andreea","family":"Ghenciu","sequence":"first","affiliation":[{"name":"Department of Functional Sciences, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ovidiu Alin","family":"Ha\u021began","sequence":"additional","affiliation":[{"name":"Discipline of Anatomy and Embriology, Medicine Faculty, Vasile Goldis Western University of Arad, Revolution Boulevard 94, 310025 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4620-3340","authenticated-orcid":false,"given":"Emil Robert","family":"Stoicescu","sequence":"additional","affiliation":[{"name":"Field of Applied Engineering Sciences, Specialization Statistical Methods and Techniques in Health and Clinical Research, Faculty of Mechanics, \u2018Politehnica\u2019 University Timi\u0219oara, Mihai Viteazul Boulevard No. 1, 300222 Timi\u0219oara, Romania"},{"name":"Department of Radiology and Medical Imaging, \u2018Victor Babe\u0219\u2019 University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Research Center for Pharmaco-Toxicological Evaluations, \u2018Victor Babe\u0219\u2019 University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2894-712X","authenticated-orcid":false,"given":"Roxana","family":"Iacob","sequence":"additional","affiliation":[{"name":"Field of Applied Engineering Sciences, Specialization Statistical Methods and Techniques in Health and Clinical Research, Faculty of Mechanics, \u2018Politehnica\u2019 University Timi\u0219oara, Mihai Viteazul Boulevard No. 1, 300222 Timi\u0219oara, Romania"},{"name":"Department of Anatomy and Embriology, \u2018Victor Babe\u0219\u2019 University of Medicine and Pharmacy Timi\u0219oara, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina Maria","family":"\u0218i\u0219u","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embriology, \u2018Victor Babe\u0219\u2019 University of Medicine and Pharmacy Timi\u0219oara, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1136\/bjophthalmol-2016-308823","article-title":"Stargardt disease: Clinical features, molecular genetics, animal models and therapeutic options","volume":"101","author":"Tanna","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","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_3","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_4","unstructured":"Rosenberg, T., Baumann, B., and Allikmets, R. (2019). Stargardt Disease: Genetics and Molecular Mechanisms. Inherited Retinal Disease: Diagnosis and Clinical Management, Elsevier."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2147\/OPTO.S226595","article-title":"Monitoring and Management of the Patient with Stargardt Disease","volume":"11","author":"Cicinelli","year":"2019","journal-title":"Clin. Optom."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"707","DOI":"10.2147\/OPTH.S241928","article-title":"The impact of inherited retinal diseases in the Republic of Ireland (ROI) and the United Kingdom (UK) from a cost-of-illness perspective","volume":"14","author":"Galvin","year":"2020","journal-title":"Clin. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/j.ophtha.2013.01.068","article-title":"The economic burden of vision loss and eye disorders among the United States population younger than 40 years","volume":"120","author":"Wittenborn","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s13167-018-0136-8","article-title":"Mental stress as consequence and cause of vision loss: The dawn of psychosomatic ophthalmology for preventive and personalized medicine","volume":"9","author":"Sabel","year":"2018","journal-title":"EPMA J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1080\/13816810.2021.1913610","article-title":"Inherited retinal diseases are the most common cause of blindness in the working-age population in Australia","volume":"42","author":"Mukhtar","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Arsenijevic, Y., Berger, A., Udry, F., and Kostic, C. (2022). Lentiviral Vectors for Ocular Gene Therapy. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14081605"},{"key":"ref_11","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_12","first-page":"196","article-title":"Genetic Diagnosis of Familial Exudative Vitreoretinopathy by Targeted Next-Generation Sequencing","volume":"42","author":"Huang","year":"2021","journal-title":"Ophthalmic Genet."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.oret.2017.03.001","article-title":"The Epidemiology of Stargardt Disease in the United Kingdom","volume":"1","author":"Ho","year":"2017","journal-title":"Ophthalmol. Retina"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/aos.14996","article-title":"Stargardt disease: Monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry","volume":"100","author":"Runhart","year":"2022","journal-title":"Acta Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, X., Chen, C., Wu, D., Tang, C., Ren, C., Yu, M., He, H., Lu, Y., Xie, H., and Xu, H. (2021). Genetic Diagnosis of Hereditary Retinal Degeneration in China Using Next-Generation Sequencing. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.643546"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1001\/jamaophthalmol.2015.5471","article-title":"Phenotypic Variation in a Family with Pseudodominant Stargardt Disease","volume":"134","author":"Huckfeldt","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1167\/tvst.9.7.33","article-title":"Factors Influencing Retinal Pigment Epithelium-Atrophy Progression Rate in Stargardt Disease","volume":"9","author":"Cicinelli","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1167\/iovs.13-13624","article-title":"Quantitative fundus autofluorescence in recessive Stargardt disease","volume":"55","author":"Burke","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Charng, J., Xiao, D., Mehdizadeh, M., Attia, M.S., Arunachalam, S., Lamey, T.M., Thompson, J.A., McLaren, T.L., De Roach, J.N., and Mackey, D.A. (2020). Deep learning segmentation of hyperautofluorescent fleck lesions in Stargardt disease. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-73339-y"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yang, S., Zhou, J., and Li, D. (2021). Functions and Diseases of the Retinal Pigment Epithelium. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.727870"},{"key":"ref_22","first-page":"3649","article-title":"Metabolic and redox signaling in the retina","volume":"74","author":"Sahel","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_23","first-page":"14963","article-title":"RPE65 is the retinoid isomerase in bovine retinal pigment epithelium","volume":"44","author":"Jin","year":"2005","journal-title":"Biochemistry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.4252\/wjsc.v13.i11.1783","article-title":"ARPE-19 conditioned medium promotes neural differentiation of adipose-derived mesenchymal stem cells","volume":"13","author":"Mannino","year":"2021","journal-title":"World J. Stem Cells"},{"key":"ref_25","first-page":"972","article-title":"Dicer reduction induces progressive gene-independent loss of functionality in Drosophila GABAergic neurons","volume":"89","author":"Mack","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_26","first-page":"7951","article-title":"Gene therapy for Stargardt disease associated with ABCA4 mutations","volume":"116","author":"Han","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1529\/biophysj.107.116202","article-title":"The dynamics of phosphodiesterase activation in rods and cones","volume":"94","author":"Reingruber","year":"2008","journal-title":"Biophys. J."},{"key":"ref_28","first-page":"1198","article-title":"Rapid-onset widespread chorioretinal atrophy in patients with pseudodominant Stargardt disease and ABCA4 mutations","volume":"133","author":"Fishman","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"ref_29","first-page":"4409","article-title":"Reductions in Serum Vitamin A in Stargardt\u2019s Patients Treated with Oral Fenretinide","volume":"53","author":"Radu","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_30","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_31","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/s41591-020-0763-1","article-title":"Initial Results from a First-in-Human Gene Therapy Trial on X-Linked Retinitis Pigmentosa Caused by Mutations in RPGR","volume":"26","author":"Xue","year":"2020","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e195752","DOI":"10.1001\/jamanetworkopen.2019.5752","article-title":"Clinical and Molecular Characterization of PROM1-Related Retinal Degeneration","volume":"2","author":"Birtel","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1167\/iovs.13-11871","article-title":"Transduction of photoreceptors with equine infectious anemia virus lentiviral vectors: Safety and biodistribution of StarGen for Stargardt disease","volume":"54","author":"Binley","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1167\/tvst.5.5.10","article-title":"Test-retest variability of functional and structural parameters in patients with Stargardt disease participating in the SAR422459 gene therapy trial","volume":"5","author":"Parker","year":"2016","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1089\/hum.2018.156","article-title":"An AAV Dual Vector Strategy Ameliorates the Stargardt Phenotype in Adult Abca4-\/-Mice","volume":"30","author":"McClements","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"ref_38","unstructured":"Trapani, I. (2018). Methods in Molecular Biology. Efficient Non-Viral Gene Therapy for Stargardt\u2019s Disease with pH-Sensitive Multifunctional Lipid ECO Plasmid DNA Nanoparticles, Association for Research in Vision and Ophthalmology."},{"key":"ref_39","first-page":"2248","article-title":"Efficient Non-viral Gene Therapy for Stargardt\u2019s Disease with pH-Sensitive Multifunctional Lipid ECO Plasmid DNA Nanoparticles","volume":"29","author":"Notario","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1172\/JCI64833","article-title":"DNA nanoparticle-mediated ABCA4 delivery rescues Stargardt dystrophy in mice","volume":"122","author":"Han","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ymthe.2019.09.010","article-title":"Non-viral Gene Therapy for Stargardt Disease with ECO\/pRHO-ABCA4 Self-Assembled Nanoparticles","volume":"28","author":"Sun","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1038\/s41436-018-0414-9","article-title":"Deep-intronic ABCA4 variants explain missing heritability in Stargardt disease and allow correction of splice defects by antisense oligonucleotides","volume":"21","author":"Sangermano","year":"2019","journal-title":"Genet. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ajhg.2018.02.008","article-title":"Identification and Rescue of Splice Defects Caused by Two Neighboring Deep-Intronic ABCA4 Mutations Underlying Stargardt Disease","volume":"102","author":"Albert","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Garanto, A., Duijkers, L., Tomkiewicz, T.Z., and Collin, R.W.J. (2018). Antisense Oligonucleotide Screening to Optimize the Rescue of the Splicing Defect Caused by the Recurrent Deep-Intronic ABCA4 Variant c.4539+2001G>A in Stargardt Disease. Investig. Ophthalmol. Vis. Sci., 10.","DOI":"10.3390\/genes10060452"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1038\/s41436-018-0420-y","article-title":"ABCA4-associated disease as a model for missing heritability in autosomal recessive disorders: Novel noncoding splice, cis-regulatory, structural, and recurrent hypomorphic variants","volume":"21","author":"Bauwens","year":"2019","journal-title":"Genet. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.scr.2018.01.014","article-title":"A2E-associated cell death and inflammation in retinal pigmented epithelial cells from human induced pluripotent stem cells","volume":"27","author":"Parmar","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1002\/stem.149","article-title":"Long-term safety and function of RPE from human embryonic stem cells in preclinical models of macular degeneration","volume":"27","author":"Lu","year":"2009","journal-title":"Stem Cells"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.stemcr.2015.04.005","article-title":"Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: Preliminary results in Asian patients","volume":"4","author":"Song","year":"2015","journal-title":"Stem Cell Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0140-6736(14)61376-3","article-title":"Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt\u2019s macular dystrophy: Follow-up of two open-label phase 1\/2 studies","volume":"385","author":"Schwartz","year":"2015","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Weiss, J.N., and Levy, S. (2021). Stem Cell Ophthalmology Treatment Study (SCOTS): Bone Marrow-Derived Stem Cells in the Treatment of Stargardt Disease. Medicines, 8.","DOI":"10.3390\/medicines8020010"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3821","DOI":"10.1167\/iovs.07-1470","article-title":"Accelerated Accumulation of Lipofuscin Pigments in the RPE of a Mouse Model for ABCA4-Mediated Retinal Dystrophies Following Vitamin A Supplementation. Invest","volume":"49","author":"Radu","year":"2008","journal-title":"Ophthalmol. Vis. Sci."},{"key":"ref_52","first-page":"2685","article-title":"TEASE: A phase 2 clinical trial assessing the tolerability and effects of oral once-a-day ALK-001 on Stargardt disease","volume":"57","author":"Scholl","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Steinhoff, J.S., Lass, A., and Schupp, M. (2021). Biological Functions of RBP4 and Its Relevance for Human Diseases. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.659977"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3892\/mmr.2022.12760","article-title":"Interplay of retinol binding protein 4 with obesity and associated chronic alterations (Review)","volume":"26","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_55","first-page":"3518","article-title":"A Phase 1b\/2 Study of the Safety and Tolerability of Tinlarebant in Adolescent STGD1 Subjects","volume":"63","author":"Grigg","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","first-page":"1026","article-title":"Safety, Tolerability, and Efficacy of Tinlarebant from the 24-Month Phase 2 study in Adolescent Patients Affected by Stargardt Disease","volume":"65","author":"Grigg","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1167\/tvst.12.2.1","article-title":"Repeatability of Quantitative Autofluorescence Imaging in a Multicenter Study Involving Patients with Recessive Stargardt Disease 1","volume":"12","author":"Dhooge","year":"2023","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.freeradbiomed.2022.02.025","article-title":"Removal of RPE lipofuscin results in rescue from retinal degeneration in a mouse model of advanced Stargardt disease: Role of reactive oxygen species","volume":"182","author":"Fang","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e00683","DOI":"10.1002\/prp2.683","article-title":"Penetration, distribution, and elimination of remofuscin\/soraprazan in Stargardt mouse eyes following a single intravitreal injection using pharmacokinetics and transmission electron microscopic autoradiography: Implication for the local treatment of Stargardt\u2019s disease and dry age-related macular degeneration","volume":"8","author":"Illing","year":"2020","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ghenciu, L.A., Ha\u021began, O.A., Bolintineanu, S.L., D\u0103nil\u0103, A.-I., Faur, A.C., Prodan-B\u0103rbulescu, C., Stoicescu, E.R., Iacob, R., and \u0218i\u0219u, A.M. (2024). Immune-Mediated Ocular Surface Disease in Diabetes Mellitus\u2014Clinical Perspectives and Treatment: A Narrative Review. Biomedicines, 12.","DOI":"10.3390\/biomedicines12061303"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ghenciu, L.A., Ha\u021began, O.A., Bolintineanu, S.L., D\u0103nil\u0103, A.-I., Iacob, R., Stoicescu, E.R., Lupu, M.A., and Olariu, T.R. (2024). Human Ocular Toxoplasmosis in Romania: History, Epidemiology, and Public Health: A Narrative Review. Microorganisms, 12.","DOI":"10.3390\/microorganisms12081541"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Pinilla, I., Maneu, V., Campello, L., Fern\u00e1ndez-S\u00e1nchez, L., Mart\u00ednez-Gil, N., Kutsyr, O., S\u00e1nchez-S\u00e1ez, X., S\u00e1nchez-Castillo, C., Lax, P., and Cuenca, N. (2022). Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications. Antioxidants, 11.","DOI":"10.3390\/antiox11061086"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/nat.2015.0573","article-title":"Reviews Fit for the Eye: Aptamers in Ocular Disorders","volume":"26","author":"Drolet","year":"2016","journal-title":"Nucleic Acid Ther."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Park, Y.G., Park, Y.S., and Kim, I.B. (2021). Complement System and Potential Therapeutics in Age-Related Macular Degeneration. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136851"},{"key":"ref_65","first-page":"1569","article-title":"Complement C5 Inhibition as a Potential Treatment for Autosomal Recessive Stargardt Disease (STGD1): Design of a Clinical Trial Assessing a Novel Treatment and Primary Outcome Measure","volume":"59","author":"Csaky","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Bavik, C., Henry, S.H., Zhang, Y., Mitts, K., McGinn, T., Budzynski, E., Pashko, A., Lieu, K.L., Zhong, S., and Blumberg, B. (2015). Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124940"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1136\/bjophthalmol-2020-317712","article-title":"Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease","volume":"106","author":"Kubota","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1097\/IAE.0b013e318265801d","article-title":"Investigation of oral fenretinide for treatment of geographic atrophy in age-related macular degeneration","volume":"33","author":"Mata","year":"2013","journal-title":"Retina"},{"key":"ref_69","first-page":"476","article-title":"Metformin Attenuates the Hallmarks of Stargardt Disease","volume":"64","author":"Farnoodian","year":"2023","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4742","DOI":"10.1073\/pnas.0737855100","article-title":"Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt\u2019s macular degeneration","volume":"100","author":"Radu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1080\/02713680701616156","article-title":"Evaluation of 4-methylpyrazole as a potential therapeutic dark adaptation inhibitor","volume":"32","author":"Jurgensmeier","year":"2007","journal-title":"Curr. Eye Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1080\/14712598.2018.1513486","article-title":"Stargardt macular dystrophy and evolving therapies","volume":"18","author":"Hussain","year":"2018","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Piccardi, M., Fadda, A., Martelli, F., Marangoni, D., Magli, A., Minnella, A.M., Bertelli, M., Di Marco, S., Bisti, S., and Falsini, B. (2019). Antioxidant Saffron and Central Retinal Function in ABCA4-Related Stargardt Macular Dystrophy. Nutrients, 11.","DOI":"10.3390\/nu11102461"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1559325818803428","DOI":"10.1177\/1559325818803428","article-title":"Acquired Resilience: An Evolved System of Tissue Protection in Mammals","volume":"16","author":"Stone","year":"2018","journal-title":"Dose-Response"},{"key":"ref_75","unstructured":"Hodge, W., Barnes, D., Schachter, H.M., Pan, Y., Lowcock, E.C., Zhang, L., Sampson, M., Morrison, A., Tran, K., and Miguelez, M. (2005). Effects of Omega-3 Fatty Acids on Eye Health: Summary. 2005 Jul, AHRQ Evidence Report Summaries."},{"key":"ref_76","first-page":"377","article-title":"A prospective, multicentre, randomised, double-blind study designed to assess the potential effects of omega-3 fatty acids supplementation in dry age-related macular degeneration or Stargardt disease","volume":"63","author":"Prokopiou","year":"2022","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_77","first-page":"29089","article-title":"Metformin Targets Abca4 to Reduce Lipofuscin Accumulation in Stargardt Disease Models","volume":"117","author":"Liu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e000326","DOI":"10.1136\/bmjophth-2019-000326","article-title":"Omega-3 fatty acids supplementation protects the retina from age-associated degeneration in aged C57BL\/6J mice","volume":"4","author":"Prokopiou","year":"2019","journal-title":"BMJ Open Ophthalmol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.omtn.2023.02.032","article-title":"Efficient correction of Abca4 variants by CRISPR-Cas9 in hiPSCs derived from stargardt disease patients","volume":"32","author":"Siles","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/s41588-021-00838-7","article-title":"Chromothripsis as an on-target consequence of CRISPR-Cas9 genome editing","volume":"53","author":"Leibowitz","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_81","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"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8859\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:36:41Z","timestamp":1760110601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,14]]},"references-count":81,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25168859"],"URL":"https:\/\/doi.org\/10.3390\/ijms25168859","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,14]]}}}