Emerging Therapies in Retinal Diseases: From Gene Therapy to Stem Cell Interventions
Main Article Content
Abstract
Retinal disorders pose a serious threat to eye health as they frequently result in blindness and reduced vision. There is hope that the treatment of many illnesses will be revolutionised by emerging medicines, especially gene therapy and stem cell approaches. This study explores the current state of these innovative therapies and how they could affect retinal disorders. By replacing or repairing damaged genes, gene therapy, which uses precise genetic modification, shows promise in treating hereditary retinal problems. Clinical trials have yielded promising results, including improvements in visual function and optimism for patients with illnesses such as choroideremia and Leber congenital amaurosis. Regenerative approaches are provided by stem cell therapies, which restore damaged retinal tissues. Numerous stem cell varieties, including as embryonic and induced pluripotent stem cells, show promise in preclinical research and early-stage clinical trials, suggesting that cell replacement techniques may be a viable means of recovering vision. On the other hand, effective delivery, long-term safety, and ethical issues provide obstacles on the path to clinical application. To fully realise the transformational potential of these medicines, it is imperative to address these obstacles. There is potential for improved visual outcomes, targeted therapies, and personalised care as gene therapy and stem cell interventions advance. These developments highlight the promising future of treating retinal illnesses.
Article Details
References
Vandenberghe, L. H., & Auricchio, A. (2019). Novel adeno-associated viral vectors for retinal gene therapy. Gene Therapy, 26(1), 10-16.
Sahel, J. A., Marazova, K., & Audo, I. (2014). Clinical characteristics and current therapies for inherited retinal degenerations. Cold Spring Harbor Perspectives in Medicine, 5(2), a017111.
Maclaren, R. E., Groppe, M., Barnard, A. R., et al. (2014). Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. The Lancet, 383(9923), 1129-1137.
Dalkara, D., Goureau, O., Marazova, K., et al. (2016). Let there be light: Gene and cell therapy for blindness. Human Gene Therapy, 27(5), 410-427.
Cideciyan, A. V., Hauswirth, W. W., Aleman, T. S., et al. (2009). Human RPE65 gene therapy for Leber congenital amaurosis: Persistence of early visual improvements and safety at 1 year. Human Gene Therapy, 20(9), 999-1004.
Singh, M. S., Charbel Issa, P., Butler, R., et al. (2013). Reversal of end-stage retinal degeneration and restoration of visual function by photoreceptor transplantation. Proceedings of the National Academy of Sciences of the United States of America, 110(3), 1101-1106.
Gagliardi, G., Ben M'Barek, K., & Goureau, O. (2019). Photoreceptor cell replacement in macular degeneration and retinitis pigmentosa: A pluripotent stem cell-based approach. Progress in Retinal and Eye Research, 71, 1-25.
Kamao, H., Mandai, M., Okamoto, S., et al. (2014). Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application. Stem Cell Reports, 2(2), 205-218.
Lukovic, D., Artero Castro, A., Delgado, A. B., et al. (2015). Human iPSC derived disease model of MERTK-associated retinitis pigmentosa. Scientific Reports, 5, 12910.
Zerti, D., Dorgau, B., Felemban, M., et al. (2020). Developing a simple method to enhance the generation of cone and rod photoreceptors in pluripotent stem cell-derived retinal organoids. Stem Cells, 38(5), 615-626.
Klassen, H., Warfvinge, K., Schwartz, P. H., et al. (2008). Isolation of progenitor cells from GFP-transgenic pigs and transplantation to the retina of allorecipients. Cloning and Stem Cells, 10(4), 391-402.
Jayakody, S. A., Gonzalez-Cordero, A., Ali, R. R., et al. (2015). Cellular strategies for retinal repair by photoreceptor replacement. Progress in Retinal and Eye Research, 46, 31-66.
Kanemura, H., Go, M. J., Shikamura, M., et al. (2014). Tumorigenicity studies of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration. PLoS One, 9(9), e85336.
Conley, S. M., Stuck, M. W., Burnett, J. L., et al. (2014). Insights into the mechanisms of macular degeneration associated with the R172W mutation in RDS. Human Molecular Genetics, 23(9), 3102-3114.
Audo, I., Mohand-Saïd, S., Dhaenens, C. M., et al. (2012). RP1 and autosomal dominant rod-cone dystrophy: Novel mutations, a review of published variants, and genotype-phenotype correlation. Human Mutation, 33(1), 73-80.
Trapani, I., Colella, P., Sommella, A., et al. (2014). Effective delivery of large genes to the retina by dual AAV vectors. EMBO Molecular Medicine, 6(2), 194-211.
Chadderton, N., Millington-Ward, S., Palfi, A., et al. (2009). Improved retinal function in a mouse model of dominant retinitis pigmentosa following AAV-delivered gene therapy. Molecular Therapy, 17(4), 593-599.
Lai, Y., Yue, Y., Liu, M., et al. (2005). Efficient in vivo gene expression by trans-splicing adeno-associated viral vectors. Nature Biotechnology, 23(11), 1435-1439.
McClements, M. E., & MacLaren, R. E. (2013). Gene therapy for retinal disease. Translational Research, 161(4), 241-254.
Wiley, L. A., Burnight, E. R., DeLuca, A. P., et al. (2016). cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness. Scientific Reports, 6, 30742.