Neuroscience and Behavioral Physiology

, Volume 49, Issue 2, pp 192–198 | Cite as

Perspectives for the Optogenetic Prosthetization of the Retina

  • M. L. FirsovEmail author

Pigmented tapetoretinal degeneration (retinitis pigmentosa, RP) is one of the most severe and widespread forms of inherited retinal degeneration. The mechanisms of occurrence of RP are significantly heterogeneous and combine a whole group of diseases with different causes affecting very diverse molecular mechanisms and cell types. Various therapeutic approaches have allowed the development of disease to be delayed to different extents, though progression has not been stopped. The last decade has therefore seen progress in several methods of prosthetization, providing partial recovery of the light sensitivity of the retina. These methods are based on two different techniques. The first proposes replacement of degenerated photoreceptors with electronic light sensors providing light-dependent excitation of living retinal neurons – bipolar or ganglion cells. The second consists of using optogenetic methods to convert a proportion of surviving neurons into pseudophotoreceptors. In the framework of this strategy, retinal cells surviving completion of the active phase of degenerative processes are artificially given the property of light sensitivity. The literature contains a wide spectrum of reports describing the successful use of optogenetic approaches to restoring vision in animal models based on inherited retinal degeneration.


retina optogenetics inherited retinal degeneration retinal prosthetization 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arshavsky, V. Y. and Burns, M. E., “Photoreceptor signaling: supporting vision across a wide range of light intensities J. Biol. Chem., 287, No. 3, 1620–1626 (2012).CrossRefPubMedGoogle Scholar
  2. Bi, A., Cui, J., Ma, Y. P., et al., “Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration,” Neuron, 50, No. 1, 23–33 (2006).CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bregestovski, P. and Maleeva, G., “Photopharmacology: a brief review using control of potassium channels as an example,” Zh. Vyssh. Nerv. Deyat., 67, No. 5 (2017).Google Scholar
  4. Busskamp, V., Duebel, J., Balya, D., et al., “Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa,” Science, 329, No. 5990, 413–417 (2010).CrossRefPubMedGoogle Scholar
  5. Caporale, N., Kolstad, K. D., Lee, T., et al., “LiGluR restores visual responses in rodent models of inherited blindness,” Mol. Ther., 19, No. 7, 1212–1219 (2011).CrossRefPubMedPubMedCentralGoogle Scholar
  6. Cehajic-Kapetanovic, J., Eleftheriou, C., Allen, A. E., et al., “Restoration of vision with ectopic expression of human rod opsin,” Curr. Biol., 25, No. 16, 2111–2122 (2015).CrossRefPubMedPubMedCentralGoogle Scholar
  7. Chang, B., Hawes, N. L., Hurd, R. E., et al., “Retinal degeneration mutants in the mouse,” Vision Res., 42, No. 4, 517–525 (2002).CrossRefPubMedGoogle Scholar
  8. Cronin, T., Vandenberghe, L. H., Hantz, P., et al., “Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter,” EMBO Mol. Med., 6, No. 9, 1175–1190 (2014).CrossRefPubMedPubMedCentralGoogle Scholar
  9. Dacey, D. M., Liao, H. W., Peterson, B. B., et al., “Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN,” Nature, 433, No. 7027, 749–754 (2005).CrossRefPubMedGoogle Scholar
  10. Delyfer, M. N., Leveillard, T., Mohand-Said, S., et al., “Inherited retinal degenerations: therapeutic prospects,” Biol. Cell, 96, No. 4, 261–269 (2004).CrossRefPubMedGoogle Scholar
  11. Farber, D. B., Flannery, J. G., and Bowes-Richman, C., “The rd mouse: 70 years of research on an animal model of inherited retinal degeneration,” Prog. Retin. Eye Res., 13, 31–64 (1994).CrossRefGoogle Scholar
  12. Gaub, B. M., Berry, M. H., Holt, A. E., et al., “Optogenetic vision restoration using rhodopsin for enhanced sensitivity,” Mol. Ther., 23, No. 10 1562–1571 (2015).CrossRefPubMedPubMedCentralGoogle Scholar
  13. Gaub, B. M., Berry, M. H., Holt, A. E., et al., “Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells,” Proc. Natl. Acad. Sci. USA, 111, No. 51, E5574 –E5583 (2014).CrossRefPubMedGoogle Scholar
  14. Goetz, G. A. and Palanker, D. V., “Electronic approaches to restoration of sight,” Rep. Prog. Phys, 79, No. 9, 096701 (2016).CrossRefPubMedPubMedCentralGoogle Scholar
  15. Gorostiza, P., Arosio, D., and Bregestovski, P., “Molecular probes and switches for functional analysis of receptors, ion channels and synaptic networks,” Front. Mol. Neuroscience, 6, 48 (2013).CrossRefGoogle Scholar
  16. Guadagni, V., Novelli, E., Piano, I., et al., “Pharmacological approaches to retinitis pigmentosa: A laboratory perspective,” Prog. Retin. Eye Res., 48, 62–81 (2015).CrossRefPubMedGoogle Scholar
  17. Hadjinicolaou, A. E., Meffin, H., Maturana, M. I., et al., “Prosthetic vision: devices, patient outcomes and retinal research,” Clin. Exp. Optom, 98, No. 5, 395–410 (2015).CrossRefPubMedGoogle Scholar
  18. Jones, B. W., Kondo, M., Terasaki, H., et al., “Retinal remodeling,” Jpn. J. Ophthalmol., 56, No. 4, 289–306 (2012).CrossRefPubMedPubMedCentralGoogle Scholar
  19. Kalloniatis, M., Nivison-Smith, L., Chua, J., et al., “Using the rd1 mouse to understand functional and anatomical retinal remodelling and treatment implications in retinitis pigmentosa: A review,” Exp. Eye Res., 150, 106–121 (2016).CrossRefPubMedGoogle Scholar
  20. Klapper, S. D., Swiersy, A., Bamberg, E., and Busskamp, V., “Biophysical properties of optogenetic tools and their application for vision restoration approaches,” Front. Syst. Neurosci., 10, 74 (2016).CrossRefPubMedPubMedCentralGoogle Scholar
  21. Kleinlogel, S., “Optogenetic user’s guide to Opto-GPCRs,” Front. Biosci., 21,794–805 (2016).CrossRefGoogle Scholar
  22. Kolb, H., Circuitry for Rod Signals through the Retina, http://webvision. Scholar
  23. Kramer, R. H., Mourot, A., and Adesnik, H., “Optogenetic pharmacology for control of native neuronal signaling proteins,” Nat. Neurosci., 16, No. 7, 816–823 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
  24. Krishnamoorthy, V., Cherukuri, P., Poria, D., et al., “Retinal remodeling: concerns, emerging remedies and future prospects,” Front. Cell. Neurosci., 10, No. 38, 1–9 (2016).Google Scholar
  25. Lagali, P. S., Balya, D., Awatramani, G. B., et al., “Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration,” Nat. Neurosci., 11, No. 6, 667–675 (2008).CrossRefPubMedGoogle Scholar
  26. Lin, B. and Peng, E. B., “Retinal ganglion cells are resistant to photoreceptor loss in retinal degeneration,” PLoS One, 8, No. 6, e68084 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
  27. Marc, R., Pfeiffer, R., and Jones, B., “Retinal prosthetics, optogenetics, and chemical photoswitches,” ACS Chem. Neuroscience, 5, No. 10, 895–901 (2014).CrossRefGoogle Scholar
  28. Mazzoni, F., Novelli, E., and Strettoi, E., “Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration,” J. Neurosci., 28, No. 52 14282–14292 (2008).CrossRefPubMedPubMedCentralGoogle Scholar
  29. Mourot, A., Kienzler, M. A., Banghart, M. R., et al., “Tuning photochromic ion channel blockers,” ACS Chem. Neuroscience, 2, No. 9, 536–543 (2011).CrossRefGoogle Scholar
  30. Nagel, G., Szellas, T., Huhn, W., et al., “Channelrhodopsin-2, a directly light-gated cation-selective membrane channel,” Proc. Natl. Acad. Sci. USA, 100, No. 24, 13940–13945 (2003).CrossRefPubMedGoogle Scholar
  31. Ostrovskii, M. A. and Kirpichnikov, M. P., “Optogenetics and vision,” Sens. Sistemy, 29, No. 4, 289–295 (2015).Google Scholar
  32. Parinot, C. and Nandrot, E. F., “A comprehensive review of mutations in the MERTK proto-oncogene,” Adv. Exp. Med. Biol., 854, 259–265 (2016).CrossRefPubMedGoogle Scholar
  33. Petrs-Silva, H., Dinculescu, A., Li, Q., et al., “Novel properties of tyrosine-mutant AAV2 vectors in the mouse retina,” Mol. Ther., 19, No. 2, 293–301 (2011).CrossRefPubMedGoogle Scholar
  34. Picaud, S. and Sahel, J. A., “Retinal prostheses: clinical results and future challenges,” C. R. Biol., 337, No. 3, 214–222 (2014).CrossRefPubMedGoogle Scholar
  35. Polosukhina, A., Litt, J., Tochitsky, I., et al., “Photochemical restoration of visual responses in blind mice,” Neuron, 75, No. 2, 271–282 (2012).CrossRefPubMedPubMedCentralGoogle Scholar
  36. Sahel, J. A., Marazova, K., and Audo, I., “Clinical characteristics and current therapies for inherited retinal degenerations,” Cold Spring Harb. Perspect. Med., 5, No. 2, a017111 (2014).CrossRefPubMedGoogle Scholar
  37. Sengupta, A., Chaffiol, A., Mace, E., et al., “Red-shifted channelrhodopsin stimulation restores light responses in blind mice, macaque retina, and human retina,” EMBO Mol. Med., 8, No. 11, 1248–1264 (2016).CrossRefPubMedPubMedCentralGoogle Scholar
  38. Shintani, K., Shechtman, D. L., and Gurwood, A. S., “Review and update: current treatment trends for patients with retinitis pigmentosa,” Optometry, 80, No. 7, 384–401 (2009).CrossRefPubMedGoogle Scholar
  39. Tochitsky, I. and Kramer, R. H., “Optopharmacological tools for restoring visual function in degenerative retinal diseases,” Curr. Opin. Neurobiol., 34, 74–78 (2015).CrossRefPubMedPubMedCentralGoogle Scholar
  40. Tochitsky, I., Polosukhina, A., Degtyar, V. E., et al., “Restoring visual function to blind mice with a photoswitch that exploits electrophysiological remodeling of retinal ganglion cells,” Neuron, 81, No. 4, 800–813 (2014).CrossRefPubMedPubMedCentralGoogle Scholar
  41. van Wyk, M., Pielecka-Fortuna, J., Lowel, S., and Kleinlogel, S., “Restoring the ON switch in blind retinas: Opto-mGluR6, a next-generation, cell-tailored optogenetic tool,” PLoS Biol, 13, No. 5, e1002143 (2015).CrossRefPubMedPubMedCentralGoogle Scholar
  42. Wert, K. J., Lin, J. H., and Tsang, S. H., “General pathophysiology in retinal degeneration,” Dev. Ophthalmol., 53, 33–43 (2014).CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Sechenov Institute of Evolutionary Physiology and BiochemistryRussian Academy of SciencesSt. PetersburgRussia

Personalised recommendations