Skip to main content
SpringerLink
Log in

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

  • Chapter
Optogenetics

  • 2268 Accesses

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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 108:7595–7600

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Berndt A, Lee SY, Ramakrishnan C et al (2014) Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science 344:420–424

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 50:23–33

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Busskamp V, Duebel J, Balya D et al (2010) Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science 329:413–417

    Article  CAS  PubMed  Google Scholar 

  • Chow BY, Han X, Dobry AS et al (2010) High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 463:98–102

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 520:1406–1423

    Article  PubMed Central  PubMed  Google Scholar 

  • 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 19:1220–1229

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 69:713–720

    Article  CAS  PubMed  Google Scholar 

  • Han X, Boyden ES (2007) Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution. PLoS One 2:e299

    Article  PubMed Central  PubMed  Google Scholar 

  • 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 5:18

    Article  PubMed Central  PubMed  Google Scholar 

  • Ivanova E, Pan Z-H (2009) Evaluation of virus mediated long-term expression of channelrhodopsin-2 in the mouse retina. Mol Vision 15:1680–1689

    CAS  Google Scholar 

  • Ivanova E, Hwang G-S, Pan Z-H et al (2010) Evaluation of AAV-mediated expression of chop2-GFP in the marmoset retina. IOVS 51:5288–5296

    Google Scholar 

  • Kleinlogel S, Feldbauer K, Dempski RE et al (2011) Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh. Nat Neurosci 14:513–518

    Article  CAS  PubMed  Google Scholar 

  • 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 11:667–675

    Article  CAS  PubMed  Google Scholar 

  • Lai HC, Jan LY (2006) The distribution and targeting of neuronal voltage-gated ion channels. Nat Rev Neurosci 7:548–562

    Article  CAS  PubMed  Google Scholar 

  • 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 4:73–79

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lanyi JK (1986) Halorhodopsin: a light-driven chloride ion pump. Annu Rev Biophys Biophys Chem 15:11–28

    Article  CAS  PubMed  Google Scholar 

  • 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 105:16009–16014

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marc RE, Jones BW, Watt CB et al (2003) Neural remodeling in retinal degeneration. Prog Retin Eye Res 22:607–655

    Article  PubMed  Google Scholar 

  • Mattis J, Tye KM, Ferenczi EA et al (2011) Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins. Nat Methods 9:159–172

    Article  PubMed Central  PubMed  Google Scholar 

  • 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 28:14282–14292

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 4:130–134

    Article  CAS  PubMed  Google Scholar 

  • Nagel G, Ollig D, Fuhrmann M et al (2002) Channelrhodopsin-1: a light-gated proton channel in green algae. Science 296:2395–2398

    Article  CAS  PubMed  Google Scholar 

  • 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 100:13940–13945

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Oesterhelt D, Stoeckenius W (1973) Functions of a new photoreceptor membrane. Proc Natl Acad Sci U S A 70:2853–2857

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Prigge M, Schneider F, Tsunoda SP et al (2012) Color-tuned channelrhodopsins for multiwavelength optogenetics. J Biol Chem 287:31804–31812

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stingl K, Bartz-Schmidt KU, Besch D et al (2013) Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS. Proc Biol Sci 280:20130077

    Article  PubMed Central  PubMed  Google Scholar 

  • Strettoi E, Pignatelli V (2000) Modifications of retinal neurons in a mouse model of retinitis pigmentosa. Proc Natl Acad Sci U S A 97:11020–11025

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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 18:266–274

    Article  CAS  PubMed  Google Scholar 

  • 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 48:3821–3826

    Article  PubMed  Google Scholar 

  • 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 90:429–436

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Sugiyama Y, Hikima T et al (2009) Molecular determinants differentiating photocurrent properties of two channelrhodopsins from chlamydomonas. J Biol Chem 284:5685–5696

    Article  CAS  PubMed  Google Scholar 

  • Wässle H (2004) Parallel processing in the mammalian retina. Nat Rev Neurosci 5:747–757

    Article  PubMed  Google Scholar 

  • Weleber RG (1994) Retinitis pigmentosa and allied disorders. In: Ryan SJ (ed) Retina. Mosby, St. Louis, pp 335–466

    Google Scholar 

  • West EL, Pearson RA, MacLaren RE et al (2009) Cell transplantation strategies for retinal repair. Prog Brain Res 175:3–21

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wietek J, Wiegert JS, Adeishvili N et al (2014) Conversion of channelrhodopsin into a light-gated chloride channel. Science 344:409–412

    Article  CAS  PubMed  Google Scholar 

  • Wu C, Ivanova E, Zhang Y et al (2013) AAV-mediated subcellular targeting of optogenetic tools in retinal ganglion cells. PLoS One 8:e66332

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yanai D, Weiland JD, Mahadevappa M et al (2007) Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa. Am J Ophthalmol 143:820–827

    Article  PubMed  Google Scholar 

  • Zhang F, Wang LP, Brauner M et al (2007) Multimodal fast optical interrogation of neural circuitry. Nature 446:633–639

    Article  CAS  PubMed  Google Scholar 

  • 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 29:9186–9196

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Kresge Eye Institute, Wayne State University School of Medicine, 4717 St. Antoine, Detroit, MI, USA

    Zhuo-Hua Pan & Anding Bi

  2. Department of Anatomy/Cell Biology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI, USA

    Zhuo-Hua Pan & Qi Lu

Authors
  1. Zhuo-Hua Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anding Bi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qi Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhuo-Hua Pan .

Editor information

Editors and Affiliations

  1. Department of Developmental Biology and Neuroscience, Tohoku University Graduate School of Life Sciences, Sendai, Japan

    Hiromu Yawo

  2. Department of Frontier Materials, Nagoya Institute of Technology, Nagoya, Aichi, Japan

    Hideki Kandori

  3. National Institutes of Natural Sciences, Tokyo, Japan

    Amane Koizumi

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Pan, ZH., Bi, A., Lu, Q. (2015). Optogenetic Approaches to Restoring Intrinsic Visual Processing Features in Retinal Ganglion Cells. In: Yawo, H., Kandori, H., Koizumi, A. (eds) Optogenetics. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55516-2_25

Download citation

Publish with us

Policies and ethics

Search

Navigation