HDAC4 nucleic acid administration to treat retinal disease
Methods for inhibiting retinal cell death by altering expression of one or more of HDAC4, HDAC5, HDAC6, HDAC7, and HIF1α in a retinal cell are provided.
1. A method of inhibiting death of a retinal cell compromised by a neurodegenerative eye disorder, comprising administering to the retina of a subject having the neurodegenerative eye disorder an isolated HDAC4 nucleic acid molecule, thereby inhibiting death of the retinal cell.
2. A method for treating or preventing a neurodegenerative eye disorder in a subject, comprising administering to the retina of said subject an isolated HDAC4 nucleic acid molecule, thereby treating or preventing said neurodegenerative eye disorder in said subject.
3. A method of inhibiting death of an isolated retinal cell compromised by a neurodegenerative eye disorder, comprising contacting said isolated retinal cell with an isolated HDAC4 nucleic acid molecule, thereby inhibiting death of the isolated retinal cell.
4. The method of claim 1 , wherein the HDAC4 nucleic acid molecule comprises a wild-type HDAC4 gene.
5. The method of claim 1 , wherein the retinal cell is a photoreceptor cell.
6. The method of claim 5 , wherein the photoreceptor cell is a rod cell.
7. The method of claim 5 , wherein the photoreceptor cell is a cone cell.
8. The method of any one of claim 1 , 2 , or 3 , wherein the retinal cell is selected from the group consisting of a bipolar cell, a rod photoreceptor cell and a cone photoreceptor cell.
9. The method of any one of claim 1 , 2 , or 3 , wherein the nucleic acid molecule is expressed in the cytoplasm.
10. The method of claim 9 , wherein the nucleic acid molecule comprises an HDAC4 gene comprising a mutation that causes the exogenous HDAC4 to be localized to the cytoplasm of the cell.
11. The method of claim 10 , wherein the HDAC4 is HDAC4-L175A.
12. The method of claim 10 , wherein the HDAC4 is HDAC4-4118.
13. The method of any one of claim 1 , 2 , or 3 , wherein the neurodegenerative eye disorder is age-related macular degeneration.
14. The method of any one of claim 1 , 2 , or 3 , wherein the neurodegenerative eye disorder is retinitis pigmentosa.
15. The method of any one of claim 1 , 2 , or 3 , wherein the nucleic acid molecule is contained within a vector.
16. The method of claim 15 , wherein the vector is selected from the group consisting of a retrovirus vector, an adenovirus vector, an adenoviral/retroviral chimera vector, an adeno-associated virus (AAV) vector, a herpes simplex virus I or II vector, a parvovirus vector, a reticuloendotheliosis virus vector, a poliovirus vector, a papillomavirus vector, a vaccinia virus vector and a lentivirus vector.
17. The method of claim 16 , wherein the vector is an AAV vector.
18. The method of claim 17 , wherein the AAV vector is an AAV 2/5 or an AAV 2/8 vector.
19. A method of inhibiting death of a bipolar cell in a subject, comprising administering to the retina of said subject an isolated HDAC6 nucleic acid molecule, thereby inhibiting death of said bipolar cell.
20. A method of inhibiting death of an isolated bipolar cell, comprising contacting said isolated bipolar cell with an isolated HDAC6 nucleic acid molecule, thereby inhibiting death of said bipolar cell.