Nucleic acid vectors encoding light-gated cation-selective membrane channels, in particular channelrhodopsin-2 (Chop2), converted inner retinal neurons to photosensitive cells in photoreceptor-degenerated retina in an animal model. Such treatment restored visual perception and various aspects of vision. A method of restoring light sensitivity to a retina of a subject suffering from vision loss due to photoreceptor degeneration, as in retinitis pigmentosa or macular degeneration, is provided. The method comprises delivering to the subject by intravitreal or subretinal injection, the above nucleic acid vector which comprises an open reading frame encoding a rhodopsin, to which is operatively linked a promoter and transcriptional regulatory sequences, so that the nucleic acid is expressed in inner retinal neurons. These cells, normally light-insensitive, are converted to a light-sensitive state and transmit visual information to the brain, compensating for the loss, and leading to restoration of various visual capabilities.

Wayne State University

Salus University

Restoration of visual responses by in vivo delivery of rhodopsin nucleic acids

Pan; Zhuo-Hua

Dizhoor; Alexander M.

The present disclosure provides neuromodulators, nucleic acid encoding thereof, and compositions thereof for endowing visual processing abilities to neuronal cells. The present disclosure further provides a method of restoring light sensitivity to degenerate retinas.

Greenberg; Kenneth P.

Werblin; Frank

The Regents of the University of California

Methods of inducing photosensitivity by targeting channelrhodopsin-2 and halorhodopsin to subcellular regions of retinal ganglion cells

A light-sensitive chimeric protein includes domains from at least two members of the G-protein-coupled-receptor (GPCR) protein super family, which are fused to yield a light-sensitive GPCR chimera capable of coupling a light signal to the signaling cascade of the metabotropic glutamate receptor 6 (mGluR6) is provided for medical therapy and pharmaceuticals for treating loss of vision, in particular resulting from retinal photoreceptor degeneration. A first GPCR family member contributes domains which mediate the light-sensitivity to the chimeric light-sensitive GPCR protein and belongs to the family of light-sensitive GPCR proteins also called photopigments. In some cases, the GPCR protein is melanopsin, in particular human melanopsin. A second of the at least two GPCR family members is mGluR6, which contributes domains for coupling the light signal to the intracellular signaling cascade of mGluR6, which is a native component of the cell membrane of ON-bipolar cells in the inner retina.

photophobia/atrophy

Restoration of visual responses by in vivo delivery of rhodopsin nucleic acids

Restoration of visual responses by in vivo delivery of rhodopsin nucleic acids

Methods of inducing photosensitivity by targeting channelrhodopsin-2 and halorhodopsin to subcellular regions of retinal ganglion cells

Light-sensitive chimeric GPCR protein

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