Decreased d-Serine Levels Prevent Retinal Ganglion Cell Apoptosis in a Glaucomatous Animal Model.

Abstract

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. 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. 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. 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.