The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Login
EN
+7 (495) 482-4118
+7 (495) 482-4329
+8 800 250-18-12
  • (toll-free number for subscriptions)
    Mon-Fri from 10 a.m. to 6 p.m.

  • © 1998-2025
+7 (495) 482-43-29
EN
All journals
Journal
Year
Year
Search result: 0

Kirpichnikov M.P.

Lomonosov Moscow State University, Faculty of Biology, 1 str. 12 Leninskie Gory, Moscow, Russian Federation, 119234;
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow, Russian Federation, 117997

Ostrovskiĭ M.A.

FGBU nauki "Institut biokhimicheskoĭ fiziki im. N.M. Émanuélia" RAN, Moskva;
Ob''edinennyĭ institut iadernykh issledovaniĭ, Dubna

Optogenetics and prosthetic treatment of retinal degeneration

Authors:

Kirpichnikov M.P., Ostrovskiĭ M.A.

More about the authors

Journal: Russian Annals of Ophthalmology. 2015;131(3): 99‑111

DOI: 10.17116/oftalma2015131399-111

Read: 3559 times

Download PDF (RU)
Contact the author
Table of contents

OPTOGENETICS AND PROSTHETIC TREATMENT OF RETINAL DEGENERATION
OPTOGENETICS AND PROSTHETIC TREATMENT OF RETINAL DEGENERATION

To cite this article:

Kirpichnikov MP, Ostrovskiĭ MA. Optogenetics and prosthetic treatment of retinal degeneration. Russian Annals of Ophthalmology. 2015;131(3):99‑111. (In Russ.)
https://doi.org/10.17116/oftalma2015131399-111

Подписка 2026 Вестник офтальмологии (Russian Annals of Ophthalmology)
МСФ на ЯМ
Использование инфографики авторами научных работ
Close metadata
Abstract:

This is a review of the current state of optogenetics-based research in the field of ophthalmology and physiology of vision. Optogenetics employs an interdisciplinary approach that amalgamates gene engineering, optics, and physiology. It involves exogenous expression of a light-activated protein in a very particular retinal cell enabling regulation (stimulation vs. inhibition) of its physiological activity. The experience with gene therapy came in very useful for optogenetics. However, unlike gene therapy, which is aimed at repairing damaged genes or replacing them with healthy ones, optogenetics is focused on protein genes delivery for further molecular control of the cell. In retina, the loss of photoreceptors is not necessarily followed by neuronal loss (at least ganglion cells remain intact), which determines the practicability of prosthetic treatment. Clinical trials can now be considered, owing to the first successful conversion of ganglion cells of mouse degenerative retinas into artificial photoreceptive cells with ON and OFF receptive fields, which is crucial for spatial vision. The following issues are reviewed here in detail: 1. Choice of cell targets within the degenerative retina. 2. Strategy of utilizing the existing light-sensitive agents and development of new optogenetic tools. 3. Gene delivery and expression in retinal cells. 4. Methods of evaluating the treatment success. 5. Selection criteria for optogenetic prosthetics. The conclusion discusses currently unsolved problems and prospects for optogenetic approaches to retinal prosthetics.

Keywords:

optogenetics
degenerative retinal diseases
technological prosthetics
biologic prosthetics
optogenetic prosthetics

Authors:

Kirpichnikov M.P.

Lomonosov Moscow State University, Faculty of Biology, 1 str. 12 Leninskie Gory, Moscow, Russian Federation, 119234;
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya St., Moscow, Russian Federation, 117997

Ostrovskiĭ M.A.

FGBU nauki "Institut biokhimicheskoĭ fiziki im. N.M. Émanuélia" RAN, Moskva;
Ob''edinennyĭ institut iadernykh issledovaniĭ, Dubna

Close metadata

References:

  1. Zrenner E, Bartz-Schmidt KU, Benav H, Besch D, Bruckmann A, Gabel VP, Gekeler F, Greppmaier U, Harscher A, Kibbel S, Koch J, Kusnyerik A, Peters T, Stingl K, Sachs H, Stett A, Szurman P, Wilhelm B, Wilke R. Subretinal electronic chips allow blind patients to read letters and combine them to words. Proceedings of Biological Sciences. 2011;278(1711):1489-1497. doi:10.1098/rspb.2010.1747
  2. da Cruz L, Coley BF, Dorn JD, Merlini F, Filley E, Christopher P, Chen FK, Wuyyuru V, Sahel J, Stanga PE, Humayun M, Greenberg RJ, Dagnelie G. The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss. Br J Ophthalmol. 2013;97:632-636.
  3. Chader GJ, Weiland J, Humayun MS. Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis. Prog Brain Res. 2009;175:317-332.
  4. Silva GA, Silva NM, Fortunato TM. Stem cell and tissue engineering therapies for ocular regeneration. Curr Stem Cell Res Ther. 2011;6(3):255-272.
  5. Bharti K, Rao M, Hull SC, Stroncek D, Brooks BP, Feigal E, van Meurs JC, Huang CA, Miller SS. Developing cellular therapies for retinal degenerative diseases. Invest Ophthalmol Vis Sci. 2014;55(2):1191-1202.
  6. Zhong X, Gutierrez C, Xue T, Hampton C, Vergara MN, Cao LH, Peters A, Park TS, Zambidis ET, Meyer JS,Gamm DM, Yau KW, Canto-Soler MV. Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Nature Communications. 2014;5:4047. doi:10.1038/ncomms5047
  7. Wu C, Ivanova E, Zhang Y, Pan Z-H. rAAV-mediated subcellular targeting of optogenetic tools in retinal ganglion cells in vivo. PLoS ONE. 2013;8(6):e66332. doi:10.1371/journal.pone.0066332
  8. Jones BW, Kondo M, Terasaki H, Lin Y, McCall M, Marc RE. Retinal remodeling. Jpn J Ophthalmol. 2012;56:289-306. doi:10.1007/s10384-012-0147-2
  9. Curcio CA, Medeiros NE, Millican CL. Photoreceptor loss in age-related macular degeneration. Invest Ophthalmol Vis Sci. 1996;37(7):1236-1249.
  10. Marc RE, Jones BW, Anderson JR, Kinard K, Marshak DW, Wilson JH, Wensel T, Lucas RJ. Neural reprogramming in retinal degeneration. Invest Ophthalmol Vis Sci. 2007;48(7):3364-3371.
  11. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368(9549):1795-1809.
  12. Busskamp V, Roska B. Optogenetic approaches to restoring visual function in retinitis pigmentosa. Current Opinion in Neurobiology. 2011;21(6):942-946. doi:10.1016/j.conb.2011.06.001
  13. Strettoi E, Pignatelli V. Modifications of retinal neurons in a mouse model of retinitis pigmentosa. Proc Natl Acad Sci USA. 2000;97(20):11020-11025.
  14. Lin Y, Jones BW, Liu A, Tucker JF, Rapp K, Luo L, Baehr W, Bernstein PS, Watt CB, Yang JH, Shaw MV, Marc RE. Retinoid receptors trigger neuritogenesis in retinal degenerations. FASEB J. 2012;26(1):81-92. doi:10.1096/fj.11-192914
  15. Nakajima Y, Moriyama M, Hattori M, Minato N, Nakanishi S. Isolation of ON bipolar cell genes via hrGFP-coupled cell enrichment using the mGluR6 promoter. J Biochem. 2009;145(6):811-818. doi:10.1093/jb/mvp038
  16. Lagali PS, Balya D, Awatramani GB, Münch TA, Kim DS, Busskamp V, Cepko CL, Roska B. Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nature Neuroscience. 2008;11(6):667-675. doi: 10.1038/nn.2117
  17. Medeiros NE, Curcio CA. Preservation of ganglion cell layer neurons in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2001;42(3):795-803.
  18. Mazzoni F, Novelli E, Strettoi E. Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration. J Neurosci. 2008;28(52):14282-14292. doi:10.1523/JNEUROSCI.4968-08.2008
  19. Bi A, Cui J, Ma YP, Olshevskaya E, Pu M, Dizhoor AM, Pan ZH. Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron. 2006;50(1):23-33.
  20. Zhang Y, Ivanova E, Bi A, Pan Z-H. Ectopic expression of multiple microbial rhodopsins restores ON and OFF light responses in the retina after photoreceptor degeneration. J Neurosci. 2009;29(29):9186-9196. doi:10.1523/JNEUROSCI.0184-09.2009
  21. Humayun MS, Dorn JD, da Cruz L, Dagnelie G, Sahel JA, Stanga PE, Cideciyan AV, Duncan JL, Eliott D, Filley E, Ho AC, Santos A, Safran AB, Arditi A, Del Priore LV, Greenberg RJ; Argus II Study Group. Interim results from the international trial of Second Sight’s visual prosthesis. Ophthalmology. 2012;119(4):779-788. doi:10.1016/j.ophtha.2011.09.028
  22. Mancuso K, Hauswirth WW, Li Q, Connor TB, Kuchenbecker JA, Mauck MC, Neitz J, Neitz M. Gene therapy for red-green colour blindness in adult primates. Nature. 2009;461(7265):784-787. doi:10.1038/nature08401
  23. Francis PJ, Mansfield B, Rose S. Proceedings of the first International Optogenetic Therapies for Vision Symposium. Transl Vis Sci Technol. 2013;2(7):4.
  24. Nirenberg S, Pandarinath C. Retinal prosthetic strategy with the capacity to restore normal vision. Proc Natl Acad Sci USA. 2012;109(37):15012-15017. doi:10.1073/pnas.1207035109
  25. Reutsky-Gefen I, Golan L, Farah N, Schejter A, Tsur L, Brosh I, Shoham S. Holographic optogenetic stimulation of patterned neuronal activity for vision restoration. Nat Commun. 2013;4:1509. doi:10.1038/ncomms2500
  26. Ostrovsky M. Molecular physiology of the visual pigment rhodopsin. Biologicheskie membrany. 2012;29(1/2):38-50. (In Russ.)
  27. Grote M, Engelhard M, Hegemann P. Of ion pumps, sensors and channels - perspectives on microbial rhodopsins between science and history. Biochim Biophys Acta. 2014;1837(5):533-545. doi:10.1016/j.bbabio.2013.08.006
  28. Shen L, Chen C, Zheng H, Jin L. The Evolutionary Relationship between Microbial Rhodopsins and Metazoan Rhodopsins. The Scientific World Journal. 2013, Article ID 435651. doi.org/10.1155/2013/435651.
  29. Deisseroth K. Optogenetics. Nat Methods. 2011;8(1):26-29. doi:10.1038/nmeth.f.324
  30. Prigge M, Schneider F, Tsunoda SP, Shilyansky C, Wietek J, Deisseroth K, Hegemann P. Color-tuned channelrhodopsins for multiwavelength optogenetics. J Biol Chem. 2012;287(38):31804-31812. doi:10.1074/jbc.M112.391185
  31. Lin JY, Knutsen PM, Muller A, Kleinfeld D, Tsien RY. ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation. Nat Neurosci. 2013;16(10):1499-1508. doi:10.1038/nn.3502
  32. Wietek J, Wiegert JS, Adeishvili N, Schneider F, Watanabe H, Tsunoda SP, Vogt A, Elstner M, Oertner TG, Hegemann P. Conversion of channelrhodopsin into a light-gated chloride channel. Science. 2014;344(6182):409-412. doi:10.1126/science.1249375
  33. Mutter M, Münch TA. Strategies for Expanding the operational range of channelrhodopsin in optogenetic vision. PLoS ONE. 2013;8(11):e81278. doi:10.1371/journal.pone.0081278
  34. Chow BY, Han X, Boyden ES. Genetically encoded molecular tools for light-driven silencing of targeted neurons. Prog Brain Res. 2012;196:49-61. doi:10.1016/B978-0-444-59426-6.00003-3
  35. Han X, Chow BY, Zhou H, Klapoetke NC, Chuong A, Rajimehr R, Yang A, Baratta MV, Winkle J, Desimone R, Boyden ES. A high-light sensitivity optical neural silencer: development and application to optogenetic control of nonhuman primate cortex. Front Syst Neurosci. 2011;5:18. doi:10.3389/fnsys.2011.00018
  36. Chow BY, Chuong AS, Klapoetke NC, Boyden ES. Synthetic physiology strategies for adapting tools from nature for genetically targeted control of fast biological processes. Methods Enzymol. 2011;497:425-443. doi:10.1016/B978-0-12-385075-1.00018-4
  37. Hattar S, Liao HW, Takao M, Berson DM, Yau KW. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science. 2002;295(5557):1065-1070.
  38. Panda S, Sato TK, Castrucci AM, Rollag MD, DeGrip WJ, Hogenesch JB, Provencio I, Kay SA. Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting. Science. 2002;298(5601):2213-2216.
  39. Panda S. Multiple photopigments entrain the Mammalian circadian oscillator. Neuron. 2007;53(5):619-621.
  40. Lin B, Koizumi A, Tanaka N, Panda S, Masland RH. Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin. Proc Natl Acad Sci USA. 2008;105(41):16009-16014. doi:10.1073/pnas.0806114105
  41. Polosukhina A, Litt J, Tochitsky I, Nemargut J, Sychev Y, De Kouchkovsky I, Huang T, Borges K, Trauner D, Van Gelder RN, Kramer RH. Photochemical restoration of visual responses in blind mice. Neuron. 2012;75(2):271-282. doi:10.1016/j.neuron.2012.05.022
  42. Caporale N, Kolstad KD, Lee T, Tochitsky I, Dalkara D, Trauner D, Kramer R, Dan Y, Isacoff EY, Flannery JG. LiGluR restores visual responses in rodent models of inherited blindness. Mol Ther. 2011;19(7):1212-1219. doi:10.1038/mt.2011.103
  43. Niescierowicz K, Caro L, Cherezov V, Vivaudou M, Moreau CJ. Functional assay for T4 lysozyme-engineered G protein-coupled receptors with an ion channel reporter. Structure. 2014;22(1):149-155. doi:10.1016/j.str.2013.10.002
  44. Maguire AM, Simonelli F, Pierce EA, Pugh ENJr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med. 2008;358(21):2240-2248. doi:10.1056/NEJMoa0802315
  45. Jacobson SG, Cideciyan AV, Ratnakaram R, Heon E, Schwartz SB, Roman AJ, Peden MC, Aleman TS, Boye SL, Sumaroka A, Conlon TJ, Calcedo R, Pang JJ, Erger KE, Olivares MB, Mullins CL, Swider M, Kaushal S, Feuer WJ, Iannaccone A, Fishman GA, Stone EM, Byrne BJ, Hauswirth WW. Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Arch Ophthalmol. 2012;130(1):9-24. doi:10.1001/archophthalmol.2011.298
  46. Vandenberghe LH, Bell P, Maguire AM, Xiao R, Hopkins TB, Grant R, Bennett J, Wilson JM. AAV9 targets cone photoreceptors in the nonhuman primate retina. PLoS ONE. 2013;8(1):e53463. doi:10.1371/journal.pone.0053463
  47. Kay CN, Ryals RC, Aslanidi GV, Min SH, Ruan Q, Sun J, Dyka FM, Kasuga D, Ayala AE, Van Vliet K, Agbandje-McKenna M, Hauswirth WW, Boye SL, Boye SE. Targeting photoreceptors via intravitreal delivery using novel, capsid-mutated AAV vectors. PLoS ONE. 2013;8(4):e62097. doi:10.1371/journal.pone.0062097
  48. Tomita H, Sugano E, Fukazawa Y, Isago H, Sugiyama Y, Hiroi T, Ishizuka T, Mushiake H, Kato M, Hirabayashi M, Shigemoto R, Yawo H, Tamai M. Visual properties of transgenic rats harboring the channelrhodopsin-2 gene regulated by the thy-1.2 promoter. PLoS ONE. 2009;4(11):e7679. doi:10.1371/journal.pone.0007679
  49. Bondar I, Minakova E, Ivanov R. Using of optical mapping by intrinsic optical signals for testing of mammalian visual cortex. Opticheskiy zhurnal. 2011;12(78):34-41. (In Russ.)
  50. Ivanov R, Bondar' I, Saltykov K, Shevelev I. The area of the optically activated zones of cat area 17 under stimulation with grids of different orientation. Zh Vyssh Nerv Deiat Im I P Pavlova. [Journal of higher nervous activity] 2006;56(4):516-522. (In Russ.)
  51. Jacobson SG, Cideciyan AV. Treatment possibilities for retinitis pigmentosa. N Engl J Med. 2010;363(17):1669-1671. doi:10.1056/NEJMcibr1007685
  52. Sakami S, Maeda T, Bereta G, Okano K, Golczak M, Sumaroka A, Roman AJ, Cideciyan AV, Jacobson SG, Palczewski K. Probing mechanisms of photoreceptor degeneration in a new mouse model of the common form of autosomal dominant retinitis pigmentosa due to P23H opsin mutations. J Biol Chem. 2011;286(12):10551-10567. doi:10.1074/jbc.M110.209759
  53. Mustafi D, Kevany BM, Genoud C, Okano K, Cideciyan AV, Sumaroka A, Roman AJ, Jacobson SG, Engel A, Adams MD, Palczewski K. Defective photoreceptor phagocytosis in a mouse model of enhanced S-cone syndrome causes progressive retinal degeneration. FASEB J. 2011;25(9):3157-3176. doi:10.1096/fj.11-186767
  54. Francis PJ, Mansfield B, Rose S. Proceedings of the First International Optogenetic Therapies for Vision Symposium. Trans Vis Sci Tech. 2013;2(7):4.
  55. Aleman TS, Soumittra N, Cideciyan AV, Sumaroka AM, Ramprasad VL, Herrera W, Windsor EA, Schwartz SB, Russell RC, Roman AJ, Inglehearn CF, Kumaramanickavel G, Stone EM, Fishman GA, Jacobson SG. CERKL mutations cause an autosomal recessive cone-rod dystrophy with inner retinopathy. Invest Ophthalmol Vis Sci. 2009;50(12):5944-5954. doi:10.1167/iovs.09-3982
  56. Aleman TS, Cideciyan AV, Aguirre GK, Huang WC, Mullins CL, Roman AJ, Sumaroka A, Olivares MB, Tsai FF, Schwartz SB, Vandenberghe LH, Limberis MP, Stone EM, Bell P, Wilson JM, Jacobson SG. Human CRB1-associated retinal degeneration: comparison with the rd8 Crb1-mutant mouse model. Invest Ophthalmol Vis Sci. 2011;52(9):6898-6910. doi:10.1167/iovs.11-7701
  57. Aguirre GK, Komáromy AM, Cideciyan AV, Brainard DH, Aleman TS, Roman AJ, Avants BB, Gee JC, Korczykowski M, Hauswirth WW, Acland GM, Aguirre GD, Jacobson SG. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation. PLoS Med. 2007;4(6):e230.
Contact the author
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

Contact us
If you have any questions, complaints or suggestions, please use this feedback form.
Email
Message
The publishing house "Media Sphere" does not provide treatment services, does not give recommendations on contacting medical institutions and specific specialists, on the prescription of medicines and dietary supplements.
Submit Application

You can become an author of one of our magazines, send a request and we will consider it in during the day.

Name
Phone
E-mail
Message
Login
Registration
E-mail
Password
Forgot Password?

Log in to the site using your account in one of the services

Password recovery
E-mail
Login
Register

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.