Optogenetics pp 353-365 | Cite as

Optogenetic Approaches to Restoring Intrinsic Visual Processing Features in Retinal Ganglion Cells

  • Zhuo-Hua PanEmail author
  • Anding Bi
  • Qi Lu


The severe loss of photoreceptor cells caused by degenerative diseases of the retina could result in partial or complete blindness . The optogenetic strategy to restoring vision involves genetically converting the surviving inner retinal neurons to photosensitive cells, thus restoring light sensitivity to the retina after photoreceptor degeneration. Proof-of-concept studies in animal models have already demonstrated that it is possible to create photosensitivity in inner retinal neurons and restore visually guided behaviors. Multiple approaches would need to be developed regarding rendering photosensitivity to particular retinal layers or cell types depending on retinal degenerative conditions. For severe retinal degenerative conditions, rendering photosensitivity to retinal ganglion cells might be the only option. This would also require restoring intrinsic visual processing features such as ON and OFF light responses, sustained and transient light responses, and center-surround antagonistic receptive fields to restore vision at the highest quality . Significant progress has been made toward achieving these goals, although challenges still remain.


Optogenetics Vision restoration Channelrhodopsins Halorhodopsin Adeno-associated virus Retinal ganglion cells ON response OFF response Center-surround receptive field 


  1. Berndt A, Schoenenberger P, Mattis J et al (2011) High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels. Proc Natl Acad Sci U S A 108:7595–7600PubMedCentralPubMedCrossRefGoogle Scholar
  2. Berndt A, Lee SY, Ramakrishnan C et al (2014) Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science 344:420–424PubMedCentralPubMedCrossRefGoogle Scholar
  3. Bi A, Cui J, Ma Y-P et al (2006) Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron 50:23–33PubMedCentralPubMedCrossRefGoogle Scholar
  4. Busskamp V, Duebel J, Balya D et al (2010) Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science 329:413–417PubMedCrossRefGoogle Scholar
  5. Chow BY, Han X, Dobry AS et al (2010) High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463:98–102PubMedCentralPubMedCrossRefGoogle Scholar
  6. Damiani D, Novelli E, Mazzoni F et al (2012) Undersized dendritic arborizations in retinal ganglion cells of the rd1 mutant mouse: a paradigm of early onset photoreceptor degeneration. J Comp Neurol 520:1406–1423PubMedCentralPubMedCrossRefGoogle Scholar
  7. Doroudchi MM, Greenberg KP, Liu J et al (2011) Virally delivered channelrhodopsin-2 safely and effectively restores visual function in multiple mouse models of blindness. Mol Ther 19:1220–1229PubMedCentralPubMedCrossRefGoogle Scholar
  8. Greenberg KP, Pham A, Werblin FS (2011) Differential targeting of optical neuromodulators to ganglion cell soma and dendrites allows dynamic control of center-surround antagonism. Neuron 69:713–720PubMedCrossRefGoogle Scholar
  9. Han X, Boyden ES (2007) Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS One 2:e299PubMedCentralPubMedCrossRefGoogle Scholar
  10. Han X, Chow BY, Zhou H et al (2011) A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex. Front Syst Neurosci 5:18PubMedCentralPubMedCrossRefGoogle Scholar
  11. Ivanova E, Pan Z-H (2009) Evaluation of virus mediated long-term expression of channelrhodopsin-2 in the mouse retina. Mol Vision 15:1680–1689Google Scholar
  12. Ivanova E, Hwang G-S, Pan Z-H et al (2010) Evaluation of AAV-mediated expression of chop2-GFP in the marmoset retina. IOVS 51:5288–5296Google Scholar
  13. Kleinlogel S, Feldbauer K, Dempski RE et al (2011) Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh. Nat Neurosci 14:513–518PubMedCrossRefGoogle Scholar
  14. Lagali PS, Balya D, Awatramani GB et al (2008) Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nat Neurosci 11:667–675PubMedCrossRefGoogle Scholar
  15. Lai HC, Jan LY (2006) The distribution and targeting of neuronal voltage-gated ion channels. Nat Rev Neurosci 7:548–562PubMedCrossRefGoogle Scholar
  16. Lamba DA, Gust J, Reh TA (2009) Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crxdeficient mice. Cell Stem Cell 4:73–79PubMedCentralPubMedCrossRefGoogle Scholar
  17. Lanyi JK (1986) Halorhodopsin: a light-driven chloride ion pump. Annu Rev Biophys Biophys Chem 15:11–28PubMedCrossRefGoogle Scholar
  18. Lin B, Koizumi A, Tanaka N et al (2008) Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin. Proc Natl Acad Sci U S A 105:16009–16014PubMedCentralPubMedCrossRefGoogle Scholar
  19. Marc RE, Jones BW, Watt CB et al (2003) Neural remodeling in retinal degeneration. Prog Retin Eye Res 22:607–655PubMedCrossRefGoogle Scholar
  20. Mattis J, Tye KM, Ferenczi EA et al (2011) Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins. Nat Methods 9:159–172PubMedCentralPubMedCrossRefGoogle Scholar
  21. Mazzoni F, Novelli E, Strettoi E (2008) Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration. J Neurosci 28:14282–14292PubMedCentralPubMedCrossRefGoogle Scholar
  22. McLaughlin ME, Sandberg MA, Berson EL et al (1993) Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa. Nat Genet 4:130–134PubMedCrossRefGoogle Scholar
  23. Nagel G, Ollig D, Fuhrmann M et al (2002) Channelrhodopsin-1: a light-gated proton channel in green algae. Science 296:2395–2398PubMedCrossRefGoogle Scholar
  24. Nagel G, Szellas T, Huhn W et al (2003) Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A 100:13940–13945PubMedCentralPubMedCrossRefGoogle Scholar
  25. Oesterhelt D, Stoeckenius W (1973) Functions of a new photoreceptor membrane. Proc Natl Acad Sci U S A 70:2853–2857PubMedCentralPubMedCrossRefGoogle Scholar
  26. Prigge M, Schneider F, Tsunoda SP et al (2012) Color-tuned channelrhodopsins for multiwavelength optogenetics. J Biol Chem 287:31804–31812PubMedCentralPubMedCrossRefGoogle Scholar
  27. Stingl K, Bartz-Schmidt KU, Besch D et al (2013) Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS. Proc Biol Sci 280:20130077PubMedCentralPubMedCrossRefGoogle Scholar
  28. Strettoi E, Pignatelli V (2000) Modifications of retinal neurons in a mouse model of retinitis pigmentosa. Proc Natl Acad Sci U S A 97:11020–11025PubMedCentralPubMedCrossRefGoogle Scholar
  29. Sugano E, Isago H, Wang Z et al (2011) Immune responses to adeno-associated virus type 2 encoding channelrhodopsin-2 in a genetically blind rat model for gene therapy. Gene Ther 18:266–274PubMedCrossRefGoogle Scholar
  30. Tomita H, Sugano E, Yawo H et al (2007) Restoration of visual response in aged dystrophic RCS rats using AAV-mediated channelopsin-2 gene transfer. Invest Ophthalmol Vis Sci 48:3821–3826PubMedCrossRefGoogle Scholar
  31. Tomita H, Sugano E, Isago H et al (2010) Channelrhodopsin-2 gene transduced into retinal ganglion cells restores functional vision in genetically blind rats. Exp Eye Res 90:429–436PubMedCrossRefGoogle Scholar
  32. Wang H, Sugiyama Y, Hikima T et al (2009) Molecular determinants differentiating photocurrent properties of two channelrhodopsins from chlamydomonas. J Biol Chem 284:5685–5696PubMedCrossRefGoogle Scholar
  33. Wässle H (2004) Parallel processing in the mammalian retina. Nat Rev Neurosci 5:747–757PubMedCrossRefGoogle Scholar
  34. Weleber RG (1994) Retinitis pigmentosa and allied disorders. In: Ryan SJ (ed) Retina. Mosby, St. Louis, pp 335–466Google Scholar
  35. West EL, Pearson RA, MacLaren RE et al (2009) Cell transplantation strategies for retinal repair. Prog Brain Res 175:3–21PubMedCentralPubMedGoogle Scholar
  36. Wietek J, Wiegert JS, Adeishvili N et al (2014) Conversion of channelrhodopsin into a light-gated chloride channel. Science 344:409–412PubMedCrossRefGoogle Scholar
  37. Wu C, Ivanova E, Zhang Y et al (2013) AAV-mediated subcellular targeting of optogenetic tools in retinal ganglion cells. PLoS One 8:e66332PubMedCentralPubMedCrossRefGoogle Scholar
  38. Yanai D, Weiland JD, Mahadevappa M et al (2007) Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa. Am J Ophthalmol 143:820–827PubMedCrossRefGoogle Scholar
  39. Zhang F, Wang LP, Brauner M et al (2007) Multimodal fast optical interrogation of neural circuitry. Nature 446:633–639PubMedCrossRefGoogle Scholar
  40. Zhang Y, Ivanova E, Bi A et al (2009) Ectopic expression of multiple microbial rhodopsins restores ON and OFF light responses in the retina after photoreceptor degeneration. J Neurosci 29:9186–9196PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2015

Authors and Affiliations

  1. 1.Department of OphthalmologyKresge Eye Institute, Wayne State University School of MedicineDetroitUSA
  2. 2.Department of Anatomy/Cell BiologyWayne State University School of MedicineDetroitUSA

Personalised recommendations