Increased Retinal Transferrin in Human and Monkey Glaucoma

Abstract

Abstract: : Purpose: To better understand the mechanisms mediating retinal ganglion cell loss in glaucoma, we compared gene expression patterns from normal retina with experimental and human glaucoma retina. Methods: Laser photocoagulation was used to produce unilateral experimental glaucoma in 3 monkeys, with resultant moderate to severe nerve damage. Gene expression profiling was undertaken with custom cDNA microarrays containing PCR products representing 10,034 retinal genes. Results: Comparison of glaucomatous with contralateral, unaffected retina demonstrated a group of genes with increased expression. Among the genes showing increased expression was the iron transport protein transferrin. By real-time PCR, the increase of transferrin was about 1.5 fold. In the same glaucomatous retina, the ferroxidase ceruloplasmin was increased about 6 fold, confirming and extending prior reports in the rat optic nerve crush model (Levin and Geszvain). Immunohistochemistry was used to examine transferrin in glaucomatous human retina (n=20). Initial results suggest that at the protein level transferrin expression is increased in the glaucomatous eyes. Labeling in both glaucomatous and normal retina was most intense in the inner limiting membrane, with lesser staining extending across the retina to the outer limiting membrane, in a pattern consistent with Muller cells. Conclusions: Increased mRNA and protein levels of transferrin and ceruloplasmin are present in human and experimental monkey glaucoma. Together, these results suggest the possible involvement of iron and copper metabolism and associated antioxidant systems in the pathogenesis of glaucoma.

Keywords: gene/expression • gene microarray • retina: neurochemistry