Gene and protein expression pilot profiling and biomarkers in an experimental mouse model of hypertensive glaucoma.

Published

Journal Article

Glaucoma is a group of genetically heterogeneous neurodegenerative disorders causing the degeneration of the ganglion neurons of the retina. Increased intraocular pressure (IOP) is a hallmark risk factor promoting the death of ganglion neurons of the retina in glaucoma. Yet, the molecular processes underlying the degeneration of these neurons by increased IOP are not understood. To gain insight into the early molecular events and discover biomarkers induced by IOP, we performed gene and protein expression profiling to compare retinas of eyes with and without high IOP in a rodent model of experimental glaucoma. This pilot study found that the IOP-mediated changes in the transcription levels of a restricted set of genes implicated in peroxisomal and mitochondrial function, modulation of neuron survival and inflammatory processes, were also accompanied by changes in the levels of proteins encoded by the same genes. With the exception of the inflammatory markers, serum amyloid-A1 (SAA1) and serum amyloid-A2 (SAA2), the IOP-induced changes in protein expression were restricted to ganglion neurons of the retina and they were detected also in the vitreous, thus suggesting an early IOP-mediated loss of ganglion cell integrity. Interestingly, SAA1 and SAA2 were induced in retinal microglia cells, whereas they were reduced in sera of IOP-responsive mice. Hence, this study defines novel IOP-induced molecular processes, biomarkers and sources thereof, and it further validates the extension of the analyses herein reported to other genes modulated by IOP.

Full Text

Duke Authors

Cited Authors

  • Walsh, MM; Yi, H; Friedman, J; Cho, K-I; Tserentsoodol, N; McKinnon, S; Searle, K; Yeh, A; Ferreira, PA

Published Date

  • August 2009

Published In

Volume / Issue

  • 234 / 8

Start / End Page

  • 918 - 930

PubMed ID

  • 19491369

Pubmed Central ID

  • 19491369

International Standard Serial Number (ISSN)

  • 1535-3702

Digital Object Identifier (DOI)

  • 10.3181/0811-RM-344

Language

  • eng

Conference Location

  • England