Abstract: Several new vector-promoter combinations to overcome the limitations associated with AAV-mediated cone transduction in the fovea are provided. The delivery modality relies on a cone-specific promoter and result in high-level transgene expression compatible with optogenetic vision restoration. Methods of expressing a polynucleotide of interest in the cone photoreceptors of a subject comprising subretinal delivery of a therapeutically effective amount of a recombinant AAV9-derived vector comprising a VP1 capsid protein as set forth in SEQ ID NO: 11 and the polynucleotide of interest under the control of the pR1.7 promoter as set forth in SEQ ID NO: 12 are also provided.

Abstract: The present invention relates to a nucleic acid sequence derived from the regulatory region of the human gamma-synuclein gene and having a promoter activity in retinal ganglion cells. The present invention also relates to expression cassettes or vectors comprising said promoter operably linked to a nucleic acid sequence encoding a polypeptide of interest as well as viral particles or host cells comprising said expression cassette or vector. The present invention also relates to the use of said expression cassettes, vectors, viral particles or cells in the treatment of ocular disease, in particular ocular disease associated with retinal ganglion cell or photoreceptor cell degeneration.

Abstract: The present invention relates to an isolated nucleic acid molecule comprising i) a nucleotide sequence coding for a hyperpolarizing light-gated ion channel or pump gene from an archeon or for a light-active fragment of said gene, or the nucleotide sequence and ii) a nucleotide sequence coding for a neurotrophic factor for use in the treatment of a retinal degenerative disease.

Abstract: Several new vector-promoter combinations to overcome the limitations associated with AAV-mediated cone transduction in the fovea are provided. The delivery modality relies on a cone-specific promoter and result in high-level transgene expression compatible with optogenetic vision restoration. Methods of expressing a polynucleotide of interest in the cone photoreceptors of a subject comprising subretinal delivery of a therapeutically effective amount of a recombinant AAV9-derived vector comprising a VP1 capsid protein as set forth in SEQ ID NO: 11 and the polynucleotide of interest under the control of the pR1.7 promoter as set forth in SEQ ID NO: 12 are also provided.

Abstract: The present invention relates to photoreceptor precursor cells comprising a heterologous nucleic acid encoding an optogenetic inhibitor. The present invention also relates to a pharmaceutical composition comprising photoreceptor precursor cells of the invention and a pharmaceutically acceptable excipient. The present invention relates to photoreceptor precursor cells or pharmaceutical composition of the invention for use in the treatment of a retinal degenerative disease, preferably a retinal degenerative disease related to a loss of function or death of photoreceptors. Finally, the present invention relates to a method for producing the photoreceptor precursor cells of the invention, comprising i) providing photoreceptor precursor cells; and ii) introducing into said precursor cells a nucleic acid encoding optogenetic inhibitor.

Abstract: Disclosed are, among other methods, methods for reactivating retinal ganglion cells in mammals by administering an effective amount of channelrhodopsins (such as ChrimsonR), or an effective amount of such channelrhodopsins (such as ChrimsonR) fused to a fluorescent protein, in the form of protein or nucleic acids, and compositions thereof. The methods may include a light stimuli level inducing RGCs response that is below radiation safety limit. The methods may include delivery by an adenoassociated virus vector. The methods may include use of a CAG promoter. The methods may result in a long term expression of an effective amount of the channelrhodopsins (such as ChrimsonR protein).

Abstract: The present invention relates to a nucleic acid sequence derived from the regulatory region of the human gamma-synuclein gene and having a promoter activity in retinal ganglion cells. The present invention also relates to expression cassettes or vectors comprising said promoter operably linked to a nucleic acid sequence encoding a polypeptide of interest as well as viral particles or host cells comprising said expression cassette or vector. The present invention also relates to the use of said expression cassettes, vectors, viral particles or cells in the treatment of ocular disease, in particular ocular disease associated with retinal ganglion cell or photoreceptor cell degeneration.

Abstract: The present invention relates to an isolated nucleic acid molecule comprising i) a nucleotide sequence coding for a hyperpolarizing light-gated ion channel or pump gene from an archeon or for a light-active fragment of said gene, or the nucleotide sequence and ii) a nucleotide sequence coding for a neurotrophic factor for use in the treatment of a retinal degenerative disease.

Abstract: The present invention relates to an isolated nucleic acid molecule comprising i) a nucleotide sequence coding for a hyperpolarizing light-gated ion channel or pump gene from an archeon or for a light-active fragment of said gene, or the nucleotide sequence and ii) a nucleotide sequence coding for a neurotrophic factor for use in the treatment of a retinal degenerative disease.

Abstract: The present invention provides an organotypic system comprising a portion of a retina containing live cells in a cultured in medium, wherein photosensitivity has been restored in at least some of said live cells. Methods of use thereof are also provided.