Optogenetic approaches to restoring visual function in retinitis pigmentosa

Retinitis pigmentosa is a hereditary eye disease that affects photoreceptors and leads to blindness. The discovery of a microbial light-gated channel and the subsequent development of similar 'optogenetic' sensors have opened the door to creating artificial photoreceptors in the remaining retinal circuits of retinitis pigmentosa retinas via gene therapy. Here we review recent studies in animal models of retinitis pigmentosa that have combined knowledge of retinal cell types, circuits and computations with the ability to equip cell types with optogenetic sensors in order to restore visual activity. We also discuss the translational potential of this therapy.

[1]  Donald J. Zack,et al.  A locus control region adjacent to the human red and green visual pigment genes , 1992, Neuron.

[2]  J. Bennett,et al.  Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice. , 2008, The Journal of clinical investigation.

[3]  Douglas S Kim,et al.  Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration , 2008, Nature Neuroscience.

[4]  Zhuo-Hua Pan,et al.  Ectopic Expression of Multiple Microbial Rhodopsins Restores ON and OFF Light Responses in Retinas with Photoreceptor Degeneration , 2009, The Journal of Neuroscience.

[5]  B. Lorenz,et al.  Gene therapy for vision loss -- recent developments. , 2010, Discovery medicine.

[6]  Toru Ishizuka,et al.  Restoration of visual response in aged dystrophic RCS rats using AAV-mediated channelopsin-2 gene transfer. , 2007, Investigative ophthalmology & visual science.

[7]  Tim Gollisch,et al.  Eye Smarter than Scientists Believed: Neural Computations in Circuits of the Retina , 2010, Neuron.

[8]  T. Badea,et al.  Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision , 2008, Nature.

[9]  A. J. Roman,et al.  Normal central retinal function and structure preserved in retinitis pigmentosa. , 2010, Investigative ophthalmology & visual science.

[10]  M Tamai,et al.  Immune responses to adeno-associated virus type 2 encoding channelrhodopsin-2 in a genetically blind rat model for gene therapy , 2011, Gene Therapy.

[11]  Edward S Boyden,et al.  Virally delivered channelrhodopsin-2 safely and effectively restores visual function in multiple mouse models of blindness. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[12]  S. Shoham,et al.  Patterned Optical Activation of Retinal Ganglion Cells , 2007, 2007 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[13]  Z. Pan,et al.  Evaluation of the adeno-associated virus mediated long-term expression of channelrhodopsin-2 in the mouse retina , 2009, Molecular vision.

[14]  F. Werblin,et al.  Differential Targeting of Optical Neuromodulators to Ganglion Cell Soma and Dendrites Allows Dynamic Control of Center-Surround Antagonism , 2011, Neuron.

[15]  C. Cepko,et al.  Stimulation of the insulin/mTOR pathway delays cone death in a mouse model of retinitis pigmentosa , 2009, Nature Neuroscience.

[16]  Eberhart Zrenner,et al.  Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration , 2008, Molecular Neurobiology.

[17]  Karl Deisseroth,et al.  Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa , 2010, Science.

[18]  Zy Li,et al.  Rod photoreceptor neurite sprouting in retinitis pigmentosa , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  Kathleen A. Marshall,et al.  Safety and efficacy of gene transfer for Leber's congenital amaurosis. , 2008, The New England journal of medicine.

[20]  W. Baehr,et al.  Naturally occurring animal models with outer retina phenotypes , 2009, Vision Research.

[21]  José-Alain Sahel,et al.  Rod-Derived Cone Viability Factor for Treating Blinding Diseases: From Clinic to Redox Signaling , 2010, Science Translational Medicine.

[22]  R. Masland,et al.  Remodeling of cone photoreceptor cells after rod degeneration in rd mice. , 2009, Experimental eye research.

[23]  Toru Ishizuka,et al.  Visual Properties of Transgenic Rats Harboring the Channelrhodopsin-2 Gene Regulated by the Thy-1.2 Promoter , 2009, PloS one.

[24]  Konrad Lehmann,et al.  Visual Function in Mice with Photoreceptor Degeneration and Transgenic Expression of Channelrhodopsin 2 in Ganglion Cells , 2010, The Journal of Neuroscience.

[25]  A. Dizhoor,et al.  Ectopic Expression of a Microbial-Type Rhodopsin Restores Visual Responses in Mice with Photoreceptor Degeneration , 2006, Neuron.

[26]  S. W. Kuffler.  Discharge patterns and functional organization of mammalian retina. , 1953, Journal of neurophysiology.

[27]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[28]  Michael A. Henninger,et al.  High-Performance Genetically Targetable Optical Neural Silencing via Light-Driven Proton Pumps , 2010 .

[29]  B. Schobert,et al.  Halorhodopsin is a light-driven chloride pump. , 1982, The Journal of biological chemistry.

[30]  Feng Zhang,et al.  Multimodal fast optical interrogation of neural circuitry , 2007, Nature.

[31]  M. Tachibana,et al.  A Key Role of Starburst Amacrine Cells in Originating Retinal Directional Selectivity and Optokinetic Eye Movement , 2001, Neuron.

[32]  Eriko Sugano,et al.  Channelrhodopsin-2 gene transduced into retinal ganglion cells restores functional vision in genetically blind rats. , 2010, Experimental eye research.

[33]  E. Bamberg,et al.  Channelrhodopsin-2, a directly light-gated cation-selective membrane channel , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Patrick Degenaar,et al.  Optobionic vision—a new genetically enhanced light on retinal prosthesis , 2009, Journal of neural engineering.

[35]  R. Masland,et al.  Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin , 2008, Proceedings of the National Academy of Sciences.

[36]  Zhuo-Hua Pan,et al.  Evaluation of AAV-mediated expression of Chop2-GFP in the marmoset retina. , 2010, Investigative ophthalmology & visual science.

[37]  Alyosha C. Molnar,et al.  Crossover inhibition in the retina: circuitry that compensates for nonlinear rectifying synaptic transmission , 2009, Journal of Computational Neuroscience.

[38]  E. Bamberg,et al.  Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh , 2011, Nature Neuroscience.

[39]  David V. Schaffer,et al.  Designer Gene Delivery Vectors: Molecular Engineering and Evolution of Adeno-Associated Viral Vectors for Enhanced Gene Transfer , 2007, Pharmaceutical Research.

[40]  C. Cepko,et al.  Electroporation and RNA interference in the rodent retina in vivo and in vitro , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[41]  E. Surace,et al.  Versatility of AAV vectors for retinal gene transfer , 2008, Vision Research.

[42]  Patrick Degenaar,et al.  Multi-site optical excitation using ChR2 and micro-LED array , 2010, Journal of neural engineering.