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1From the Laboratory of Molecular and Developmental Biology, National Eye Institute, Bethesda, Maryland; 3Children’s National Medical Center, Washington, DC; the 4Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, Arizona; and 5The Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon Health Science University, Portland, Oregon.
PURPOSE. The goal of this study was to identify altered patterns of retinal mRNA expression after experimental elevation of intraocular pressure (IOP) in a rat glaucoma model.
METHODS. Brown Norway rats (N = 16) received unilateral episcleral vein injection of hypertonic saline to elevate IOP. IOP was monitored daily by handheld tonometer, and retinas were collected 8 days and 5 weeks after surgery. Comparison of mRNA levels between experimental and fellow retinas was made using gene microarrays (rat U34A rat arrays; Affymetrix, Santa Clara, CA). Semiquantitative RT-PCR was used to confirm selected results from array analysis and to compare with alterations after optic nerve transection.
RESULTS. IOP elevation for 5 weeks resulted in reproducible changes in levels of 81 mRNAs. Of these, 74 increased, whereas only 7 decreased. The expression levels of 27 of these same messages were changed after 8 days of IOP elevation. In addition, four other genes demonstrated altered expression after the shorter period of elevated IOP exposure. Approximately half of the mRNAs with altered expression were associated with either neuroinflammatory responses or apoptosis. For 25 of the selected functionally relevant messages altered by array analysis, the alterations were confirmed by semiquantitative RT-PCR. The levels of 24 of 25 selected messages were also changed after optic nerve transection.
CONCLUSIONS. The activation of glia and the complement system after IOP elevation, which is similar to that described in several neurodegenerative diseases and after optic nerve transection, suggests that this rat glaucoma model could be used to evaluate the neuroprotective potential of therapeutic agents that target these processes.
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