Czech and Slovak Ophthalmology 135 10.31348/2019/6/1 Review Innovative Strategies for Treating Retinal Diseases Straňák Zbyněk https://orcid.org/0000-0002-3175-7212 Kousal Bohdan Ardan Taras https://orcid.org/0000-0003-2334-6728 Veith Miroslav https://orcid.org/0000-0001-6254-436X 12 6 2020 6 1

Objective: The aim of this comprehensive paper is to acquaint the readers with innovative approaches in the treatment of retinal diseases, which could in the coming years to get into clinical practice. Retinal prostheses, retinal pigment epithelial (RPE) transplantation, gene therapy and optogenetics will be described in this paper.Methodology: Describing the basic characteristics and mechanisms of different types of therapy and subsequently literary minireview clarifying the current state of knowledge in the area.Results: Retinal prostheses, RPE transplantation, gene therapy and optogenetics offer yet unexplored possibilities and are considered as the future of treatment of retinal diseases where classical pharmacotherapy or surgical treatment are no longer sufficient. However, all these methods challenge not only in the innovative technical implementation itself, but also for the ethical, administrative and economic demands.Conclusion: There will be certainly interesting development in the treatment of retinal diseases, but it is not possible to fully estimate which modality of treatment will be dominant in the future.

 optogenetics induced pluripotent cells retinal prostheses gene therapy References Ahuja, AK., Yeoh, J., Dorn, JD., et al.: Factors Affecting Perceptual Threshold in Argus II Retinal Prosthesis Subjects. Transl Vis Sci Technol, 2; 2013: 1. Bainbridge, JWB., Mehat, MS., Sundaram, V., et al.: Long- -term effect of gene therapy on Leber’s congenital amaurosis. N Engl J Med, 372; 2015: 1887–1897. Bloch, E., Luo, Y., da Cruz, L.: Advances in retinal prosthesis systems. Ther Adv Ophthalmol, 11; 2019: 1–16. Boye, SE., Boye, SL., Lewin, AS., et al.: A comprehensive review of retinal gene therapy. Mol Ther J Am Soc Gene Ther, 21; 2013: 509–519. Bressler, NM., Bressler, SB., Fine, SL.: Age-related macular degeneration. Surv Ophthalmol, 32; 1988: 375–413. Carr, A-JF., Smart, MJK., Ramsden, CM., et al.: Development of human embryonic stem cell therapies for age-related macular degeneration. Trends Neurosci, 36; 2013: 385–395. Cideciyan, AV.: Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res, 29; 2010: 398–427. da Cruz, L., Fynes, K., Georgiadis, O., et al.: Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. Nat Biotechnol, 36; 2018: 328–337. Dudakova, L., Kousal, B., Kolarova, H., et al.: Gene therapy for inherited retinal and opticnerve disorders: current knowledge. Cesk Slov Oftalmol. 72; 2016; 128–136. Duebel, J., Marazova, K., Sahel, J-A.: Optogenetics. Curr Opin Ophthalmol, 26; 2015: 226–232. Edwards, TL., Cottriall, CL., Xue, K., et al.: Assessment of the Electronic Retinal Implant Alpha AMS in Restoring Vision to Blind Patients with End-Stage Retinitis Pigmentosa. Ophthalmology, 125; 2018: 432–443. Flood, MT., Gouras, P., Kjeldbye, H.: Growth characteristics and ultrastructure of human retinal pigment epithelium in vitro. Invest Ophthalmol Vis Sci, 19; 1980: 1309–1320. Gu, SM., Thompson, DA., Srikumari, CR., et al.: Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. Nat Genet, 17; 1997: 194–197. Hauswirth, WW., Aleman, TS., Kaushal, S., et al.: Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther, 19; 2008: 979–990. Ho, AC., Humayun, MS., Dorn, JD., et al.: Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind. Ophthalmology, 122; 2015: 1547–1554. Chen, FK., Patel, PJ., Uppal, GS., et al.: Long-term outcomes following full macular translocation surgery in neovascular age-related macular degeneration. Br J Ophthalmol, 94; 2010: 1337–1343. Kaufmann, KB., Buning, H., Galy, A., et al.: Gene therapy on the move. EMBO Mol Med, 5; 2013: 1642–1661. Kousal, B., Ďuďáková, Ľ., Moravíková, J., et al.: Vzácná oční onemocnění v oftalmologické praxi. Oftalmol Praxi, 2018: 7–11. Kozak, I., Stranak, Z., Popelka, S., et al.: Safety and feasibility of new nanofiber subretinal delivery system with injector for RPE cell transplantation. Invest Ophthalmol Vis Sci, 59; 2018: 5670–5670. Kvanta, A., Grudzinska, MK.: Stem cell-based treatment in geographic atrophy: promises and pitfalls. Acta Ophthalmol (Copenh), 92; 2014: 21–26. Lee, E., MacLaren, RE.: Sources of retinal pigment epithelium (RPE) for replacement therapy. Br J Ophthalmol, 95; 2011: 445–449. Lorach, H., Goetz, G., Smith, R., et al.: Photovoltaic restoration of sight with high visual acuity. Nat Med, 21; 2015: 476–482. Mace, E., Caplette, R., Marre, O., et al.: Targeting channelrhodopsin-2 to ON-bipolar cells with vitreally administered AAV Restores ON and OFF visual responses in blind mice. Mol Ther J Am Soc Gene Ther, 23; 2015: 7–16. Maguire, AM., Simonelli, F., Pierce, EA., et al.: Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med, 358; 2008: 2240–2248. Mali, S.: Delivery systems for gene therapy. Indian J Hum Genet, 19; 2013: 3–8. Mandai, M., Watanabe, A., Kurimoto, Y., et al.: Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration. N Engl J Med, 376; 2017: 1038–1046. Misra, S.: Human gene therapy: a brief overview of the genetic revolution. J Assoc Physicians India, 61; 2013: 127–133. Nanduri, D., Fine, I., Horsager, A., et al.: Frequency and amplitude modulation have different effects on the percepts elicited by retinal stimulation. Invest Ophthalmol Vis Sci, 53; 2012: 205–214. von Noorden, GK.: Application of basic research data to cli - nical amblyopia. Ophthalmology, 85; 1978: 496–504. Parolini, B., Di Salvatore, A., Pinackatt, SJ., et al.: Long-term results of autologous retinal pigment epithelium and choroid transplantation for the treatment of exudative and atrophic maculopathies. Retina, 2018. Popelka, S., Studenovska, H., Abelova, L., et al.: A frame- -supported ultrathin electrospun polymer membrane for transplantation of retinal pigment epithelial cells. Biomed Mater Bristol Engl, 10; 2015: 045022. Ramsden, CM., Powner, MB., Carr, A-JF., et al.: Stem cells in retinal regeneration: past, present and future. Dev Camb Engl, 140; 2013: 2576–2585. Schwartz, SD., Tan, G., Hosseini, H., et al.: Subretinal Transplantation of Embryonic Stem Cell-Derived Retinal Pigment Epithelium for the Treatment of Macular Degeneration: An Assessment at 4 Years. Invest Ophthalmol Vis Sci, 57; 2016: ORSFc1-9. Simunovic, MP., Shen, W., Lin, JY., et al.: Optogenetic approaches to vision restoration. Exp Eye Res, 178; 2019: 15–26. Stingl, K., Bartz-Schmidt, KU., Besch, D., et al.: Arteficial vision with wirelessly powered subretinal electronic implant alpha-IMS. Proc Biol Sci, 280; 2013: 1–8. Takahashi, K., Yamanaka, S.: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126; 2006: 663–676. Tezel, TH., Kaplan, HJ., Del Priore, LV.: Fate of human re - tinal pigment epithelial cells seeded onto layers of human Bruch’s membrane. Invest Ophthalmol Vis Sci, 40; 1999: 467–476. Wang, D., Gao, G.: State-of-the-art human gene therapy: part II. Gene therapy strategies and clinical applications. Discov Med, 18; 2014: 151–161. Yue, L., Weiland, JD., Roska, B., et al.: Retinal stimulation strategies to restore vision: Fundamentals and systems. Prog Retin Eye Res, 53; 2016: 21–47. van Zeeburg, EJT., Maaijwee, KJM., Missotten, TOAR., et al.: A free retinal pigment epithelium-choroid graft in patients with exudative age-related macular degeneration: results up to 7 years. Am J Ophthalmol, 153; 2012: 120-127.e2. Zeng, H., Sanes, JR.: Neuronal cell-type classification: challenges, opportunities and the path forward. Nat Rev Neurosci, 18; 2017: 530–546. Zrenner, E., Bartz-Schmidt, KU., Benav, H., et al.: Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc Biol Sci, 278; 2011: 1489–1497. Many thank to Mgr. Štěpánek Eliška Straňáková for preparing Figures 1, 2, 3 and 5