Decreased D-serine levels prevent retinal ganglion cell apoptosis in a glaucomatous animal model

Abstract

PURPOSE. The purpose of this study was to determine D-Serine and D-Serine synthetase serine racemase (SR) expression and whether decreased D-Serine expression has protective effects on retinal ganglion cells (RGCs) in a glaucomatous animal model. METHODS. The rat chronic intraocular hypertension (COH) model was generated as a glaucomatous animal model by cauterizing three episcleral veins. Quantitative analysis of RGC survival was determined by the counting of retrograde FluoroGold-labeled RGCs. The level of D-Serine in the retinas and aqueous humor was determined by Ultra High Performance Liquid Chromatography coupled to triple-quadrupole Mass Spectrometry (UHPLC-MS/MS). Retinal expression of serine racemase (SR) protein was determined by immunohistochemistry and Western blot analysis. The TUNEL assay was used to detect cell apoptosis. RESULTS. The content of D-Serine increased significantly in the glaucomatous retina of the COH model 2 weeks after surgery compared with the control retina. D-Serine synthetase SR expression in the right glaucomatous eye increased slightly after surgery compared with that in the left control eye and remained at this high level for 6 weeks after surgery. SR-positive cells were located mainly in the ganglion cell layer (GCL) of the retina. D-Amino acid oxidase (DAAO) treatment significantly increased RGC survival in the glaucomatous eyes, and the TUNEL assay was used to confirm that DAAO reduced the number of TUNEL-positive cells in glaucomatous eyes. However, excess D-Serine could not exacerbate RGC loss in the COH model. CONCLUSIONS. Increased D-Serine and SR expressions in the retina of the COH model were detected. DAAO treatment significantly increased RGC survival in the glaucomatous eyes. These results suggest that decreased D-Serine expression has protective effects on RGCs.