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C. Stowell, B. Arbogast, G. Williams, G. Cioffi, C. Burgoyne, A. Zhou; Retinal Proteomic Change Following Unilateral Optic Nerve Transection and Early Experimental Glaucoma in Non-Human Primate (NHP) Eyes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):871.
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To characterize changes in protein expression profiles in the retina of NHPs after IOP-related (early experimental glaucoma, EEG) or non-IOP-related (optic nerve transection, ONT) axon loss.
Three weeks after ONT or in EEG, at the onset of reproducible ONH surface change (3 to 4 weeks after the onset of mild IOP (peak IOP <25 mmHg, n=2 animals) and high IOP (peak IOP >40 mmHg, n=2 animals) laser induced elevation) both eyes of each NHP were enucleated under deep pentobarbital anesthesia. All eyes were dissected and flash frozen on dry ice. Retinal tissues from each eye were homogenized, subjected to trypsin digestion, and analyzed with a label-free quantitative UPLC QTOF mass spectrometry (MS) system (Waters Corp, Milford, MA). For each eye, amounts of individual proteins, in fmol, were determined in reference to an internal standard and ratios of each protein in ONT or EEG eye compared to its contra lateral normal were determined. A ratio ≥ 1.3 and ≤ 0.7 was defined as a change. Proteins that showed a change in at least 2 of 3 ONT, 3 of 4 EEG, 2 of 2 mild IOP EEG or 2 of 2 high IOP EEG eyes were used for further bioinformatic analyses with the assistance of the MetaCore (GeneGo Inc) or the PANTHER programs.
To date, a total of 200 ONT and 210 EEG proteins were identified and quantified. The number of up- and down regulated proteins and the major biological process associated with the proteins for each comparison are reported in the Table. All 4 of the up-regulated mild IOP EEG proteins were down regulated in high IOP EEG and 4 of the 7 down-regulated mild IOP EEG proteins were up regulated in high IOP EEG. Approximately 20% of the up- and 25% of the down-regulated proteins in high IOP EEG shared directional changes with ONT, while mild IOP EEG and ONT were essentially different.
Proteomic changes in the retina of high IOP EEG are substantially different from mild IOP EEG, while an overlap in changes (i.e. cytoskeleton remodeling processes) were observed between high IOP EEG and ONT. These data suggest a potential role for cytoarchitectural changes at the onset of retinal damage.
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