Proteomic Analysis of the Trabecular Meshwork of Rats in a Steroid-Induced Ocular Hypertension Model: Downregulation of Type I Collagen C-Propeptides

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Abstract
To investigate global protein expression profiles in the trabecular meshwork (TM) of normal and glucocorticoid-induced ocular hypertensive rat eyes by proteomic analysis, which has not yet been conducted to date. A rat ocular hypertension model was produced by topical application of dexamethasone (DEX) for 4 weeks. Age-matched untreated rats served as controls. Intraocular pressure (IOP) was monitored by an electronic tonometer. TM protein expression profiling and protein identification was carried out by a two-dimensional fluorescence differential gel electrophoresis (2-D DIGE) system and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, respectively. In DEX-treated rats, average IOP was elevated significantly, as compared with controls. By the DEX treatment, 14 TM protein spots were up- or downregulated consistently in 2-D DIGE analyses. Proteins exhibiting more than 2-fold statistically significant change were identified by MALDI-TOF mass spectrometry. alpha A-Crystallin and beta A(3)-crystallin were upregulated, while the C-propeptides of type I collagen were downregulated. Relatively short-term glucocorticoid application induced alteration in the expression of a number of proteins, including downregulation of type I collagen C-propeptides. This could reflect impaired collagen turnover in the TM of glucocorticoid-treated eyes.