Compositions and methods for preserving cells of the eye

Abstract

The invention provides a method of preserving ocular cells in a patient having or at risk of developing glaucoma. In particular, microglial cell activation can be decreased, oligodendrocyte loss can be reduced, and/or the viability of retinal ganglion cells can be preserved by administering a selective TNFR2 antagonist to an individual having or at risk of developing glaucoma.

1 . A method for preserving the viability of a retinal ganglion cell, the method comprising administering in an amount sufficient to preserve the viability of a retinal ganglion cell in a patient having or at risk of developing glaucoma a selective inhibitor of TNFR2 function selected from the group consisting of a substance that selectively binds to TNFR2 and blocks binding of TNFα thereto, a substance that reduces TNFR2 expression, and a substance that reduces TNFR2 signal transduction when TNFα is bound thereto. 
     
     
         2 . The method of  claim 1 , wherein the substance that selectively binds to TNFR2 and blocks binding of TNFα thereto comprises an antibody. 
     
     
         3 . The method of  claim 2 , wherein the antibody comprises mAb226. 
     
     
         4 . The method of  claim 1 , wherein the substance that reduces TNFR2 expression comprises siRNA. 
     
     
         5 . The method of  claim 4 , wherein the siRNA comprises siRNA for TNFR2 from expression plasmid pKD-TNFR2-v2. 
     
     
         6 . The method of  claim 1 , wherein the substance that reduces TNFR2 expression comprises IFN-gamma. 
     
     
         7 . The method of  claim 1  wherein the substance that reduces TNFR2 signal transduction when TNFα is bound thereto comprises at least one of c-IAP1, Ankyrin repeat and SOCS box (ASB)-3, and amino acids 87-501 of native TRAF2. 
     
     
         8 . A method for preserving the viability of a retinal ganglion cell, the method consisting essentially of administering a selective TNFR2 antagonist in an amount sufficient to preserve the viability of a retinal ganglion cell in a patient having or at risk of developing glaucoma. 
     
     
         9 . The method of  claim 8 , wherein the selective TNFR2 antagonist comprises at least one of mAb226, anti-TNFR2 Ab, mouse TNFR2 pAb, siRNA for TNFR2, siRNA for TNFR2 from expression plasmid pKD-TNFR2-v2, IFN-gamma, c-IAP1, Ankyrin repeat and SOCS box (ASB)-3, 80M2 or utr-1 mAbs, amino acids 87-501 of native TRAF2, certain anti-TRAF antibodies, and TNF mutant protein specific for TNFR2. 
     
     
         10 . A method for preserving the viability of a retinal ganglion cell, the method comprising administering a selective TNFR2 antagonist in an amount sufficient to preserve the viability of a retinal ganglion cell in a patient having or at risk of developing glaucoma. 
     
     
         11 . The method of  claim 10 , wherein the selective TNFR2 antagonist comprises at least one of mAb226, anti-TNFR2 Ab, mouse TNFR2 pAb, siRNA for TNFR2, siRNA for TNFR2 from expression plasmid pKD-TNFR2-v2, IFN-gamma, c-IAP1, Ankyrin repeat and SOCS box (ASB)-3, 80M2 or utr-1 mAbs, amino acids 87-501 of native TRAF2, certain anti-TRAF antibodies, and TNF mutant protein specific for TNFR2.