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(Investigative Ophthalmology and Visual Science. 2004;45:1410-1417.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.03-0872
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Increased Expression of Iron-Regulating Genes in Monkey and Human Glaucoma

Ronald H. Farkas,1,2 Itay Chowers,1,2 Abigail S. Hackam,1,2 Masaki Kageyama,3 Robert W. Nickells,4 Deborah C. Otteson,1,2 Elia J. Duh,2 Chenwei Wang,1,2 Danielle F. Valenta,2 Tushara L. Gunatilaka,1,2 Mary E. Pease,2 Harry A. Quigley,2 and Donald J. Zack1,2,5,6,7

1From the Guerrieri Center for Genetic Engineering and Molecular Ophthalmology and the 2Department of Ophthalmology, Wilmer Ophthalmological Institute, Baltimore, Maryland; the 5Departments of Neuroscience and 6Molecular Biology and Genetics, and the 7McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland; 3Santen Pharmaceuticals, Inc., Osaka, Japan; and the 4Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin.

PURPOSE. To understand the mechanisms mediating retinal ganglion cell loss in glaucoma, the gene expression patterns were compared for transferrin, ceruloplasmin, and ferritin between normal and glaucomatous retina in monkey and human eyes.

METHODS. Laser photocoagulation was used to produce unilateral experimental glaucoma in monkeys. Gene expression was assessed by in situ hybridization and quantitative reverse transcription polymerase chain reaction (PCR). Immunohistochemistry was used to examine the retinal expression of iron-related proteins in the retina in experimental monkey glaucoma and human glaucoma.

RESULTS. Comparison of glaucomatous with control monkey retinas demonstrated increased mRNA expression of transferrin, ceruloplasmin, and ferritin heavy and light chains. In situ hybridization localized retinal gene expression of transferrin mainly to the inner nuclear layer and ferritin to both the inner and outer nuclear layers. Immunohistochemical examination of monkey and human glaucoma for these iron-related proteins demonstrated increases at the protein level.

CONCLUSIONS. Increased mRNA and protein levels of the iron-regulating proteins transferrin, ceruloplasmin, and ferritin are present in glaucoma. Together, these results suggest the involvement of iron and copper metabolism and associated antioxidant systems in the pathogenesis of glaucoma.




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