Purchase this article with an account.
Molly M. Walsh, Arjun Saha, Mason Webb, Paulo A. Ferreira; The Impact of Aging on Retinal Gene Expression in a Mouse Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4159.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Increased intraocular pressure (IOP) is a hallmark risk factor for the development of glaucoma . In addition, advanced age is yet another major risk factor. Though several contributors including changes in vasculature, connective tissue of the optic nerve head, oxidative stress and mitochondrial changes have been implicated in the pathophysiology, the specific molecular mechanisms underlying the degeneration of these neurons by increased IOP are not well understood. To gain insight into the early molecular events induced by elevated IOP and aging, we performed gene expression profiling to compare retinas in young and old mice.
10 week old and retired breeder C57Bl6 mice were injected with hypertonic saline into their episcleral vein. Intraocular pressures were obtained weekly with the TonoLab device. After intraocular pressures were elevated for 3 weeks, the mice were sacrificed. Retinas were removed and RNA was isolated. Microanalysis was performed using the Affymetrix 1.0 ST microchip.Immuonhistochemistry and western blots were used to confirm gene expression changes at a protein level. Differences in gene expression between the two groups were then analyzed.
Significant changes (>2 fold change) were found in the expression of 255 genes (241 up, 14 down) that were unique to the younger mice. There was a unique group of genes for the older population as well, including 94 upregulated and 12 down-regulate. In addition, there were 96 genes which were similarly affected between both the young and old groups. In the olh hypertonic saline der mouse population, genes related to tyrosine metabolism, glutathione metabolism, cell adhesion-tight junction molecules, and mitochondrial functions were most notably affected. Immunological responses including the classical, alternative, and lectin-induced complement pathways were among those common to both groups.
This study has identified several pathways of interest involved in the retinal pathophysiology of glaucoma, specifically with increased aging, and will serve to identify potential targets which can be used to develop novel therapeutics for the treatment of glaucoma.
This PDF is available to Subscribers Only