Methods and compositions for detecting and treating retinal diseases

Abstract

The invention discloses multiple genes related to age-related macular degeneration (AMD) and/or phagocytosis by RPE cells of the eye, and methods and compositions for detecting and treating AMD and other retinal degenerative conditions based on these phagocytosis-related and/or AMD-related genes. Also provided are animal models useful for testing therapeutic compounds and treatment protocols for AMD, and gene arrays including polymorphic variants of phagocytosis-related and/or AMD-related genes, useful for genetic screening of nucleic acid samples from subjects to obtain profiles of polymorphic variant sequences in a plurality of genes associated with AMD.

1 . A method for treating a subject having or at risk of developing a retinal or choroidal degenerative disease or condition comprising administering to said subject an agent that modulates the expression or activity of an AMDP-related or phagocytosis-related gene. 
     
     
         2 . The method of  claim 1 , wherein said AMDP-related or phagocytosis-related gene is selected from the group consisting of human unknown PHG-1; prostaglandin D2 synthase; myelin basic protein; human unknown PHG-4; human unknown PHG-5; human peanut-like 2/septin 4; coactosin-like 1; clusterin; casein kinase 1 epsilon; ferritin heavy polypeptide 1; metargidin; human unknown PHG-13; retinaldehyde binding protein 1; actin gamma 1; matrix metalloproteinase, membrane-associated 1 (MT1-MMP); SWI/SNF related/OSA-1 nuclear protein; and human unknown AMDP-3; said AMDP-related or phagocytosis-related genes comprising the respective nucleotide sequences identified as SEQ ID NOS:1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and 17. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein said retinal or choroidal degenerative disease or condition is age-related macular degeneration (AMD). 
     
     
         5 - 8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein said agent contacts a retinal cell type selected from a photoreceptor, an RPE cell, or a Muller cell, or a cell type of the choroid selected from an endothelial cell, a smooth muscle cell, a leukocyte, a macrophage, a melanocyte or a fibroblast. 
     
     
         10 - 12 . (canceled) 
     
     
         30 . A method of treating a subject having or at risk of developing a retinal or choroidal degenerative disease or condition comprising administering to said subject a vector that includes a nucleic acid encoding a wild type or polymorphic variant of an AMDP-related or phagocytosis-related protein. 
     
     
         31 . A composition for prevention or treatment of a retinal or choroidal degenerative disease or condition in a subject, the composition comprising an agent that blocks the expression or activity of an AMDP-related or phagocytosis-related gene or protein. 
     
     
         32 . The composition of  claim 31 , wherein said gene or protein is MT1-MMP, prostaglandin D2 synthase, or AMDP-3. 
     
     
         33 - 34 . (canceled) 
     
     
         35 . A nonhuman transgenic animal comprising an isolated nucleic acid construct, wherein said construct causes overexpression in at least one cell type of said animal of MT1-MMP, prostaglandin D2 synthase, or AMDP-3. 
     
     
         36 . The transgenic animal of  claim 35 , wherein said overexpression is conditionally controlled. 
     
     
         37 . The transgenic animal of  claim 35 , wherein said cell type is a retinal cell type selected from the group of consisting of a photoreceptor, an RPE cell, and a Muller cell, or a choroidal cell type selected from the group consisting of an endothelial cell, a smooth muscle cell, a leukocyte, a macrophage, a melanocyte, and a fibroblast. 
     
     
         38 - 44 . (canceled) 
     
     
         45 . An isolated nucleic acid encoding a phagocytosis-related protein, comprising a nucleotide sequence selected from the group consisting of SEQ ID NOS:1, 4, 5, 12, and 17. 
     
     
         46 - 52 . (canceled) 
     
     
         53 . The method of  claim 1 , wherein the agent is administered to the eye. 
     
     
         54 . The method of  claim 53 , wherein the agent is administered by intraocular injection.