ELEVATED GAMMA-AMINOBUTYRIC-ACID, GLUTAMATE, AND VASCULAR ENDOTHELIALGROWTH-FACTOR LEVELS IN THE VITREOUS OF PATIENTS WITH PROLIFERATIVE DIABETIC-RETINOPATHY

Objective: To examine the relative levels of gamma-aminobutyric acid ( GABA), glutamate, and vascular endothelial growth factor (VEGF) in the vitreous of nondiabetic and diabetic patients. Methods: Undiluted vit reous samples were obtained from 22 patients with proliferative diabet ic retinopathy (PDR) and 28 patients without diabetes who underwent pa rs plana vitrectomy. Simultaneous venous blood samples also were obtai ned. Amino acid concentrations were determined using sensitive high-pe rformance liquid chromatography, and VEGF levels by quantitative enzym e-linked immunosorbent assay. Hemoglobin concentrations in the blood a nd vitreous were determined using spectrophotometry. Results: The leve l of GABA in the vitreous of patients with PDR, 29.4+/-7.8 mu mol/L, w as significantly higher than in controls (18.4+/-5.5 mu mol/L) (P=.004 ). The vitreous concentration of glutamate was higher in patients with PDR (24.7+/-14.0 mu mol/L) compared with controls (9.1+/-5.1 mu mol/L ) (P<.001). Vitreous VEGF level was significantly higher in patients w ith PDR (1759+/-1721 pg/mL) compared with controls (27+/-65 pg/mL) (P< .001). There were moderately strong correlations between GABA and VEGF levels (r=0.68) and glutamate and VEGF levels (r=0.43). Elevated GABA , glutamate, and VEGF levels also correlated strongly with the presenc e of PDR. Correcting for possible introduction of these molecules by v itreous hemorrhage did not significantly alter these findings. Conclus ions: Levels of glutamate potentially toxic to retinal ganglion cells are found in the vitreous of patients with PDR: Elevated vitreous GABA may reflect amacrine cell dysfunction and underlie electroretinograph ic oscillatory potential abnormalities seen in diabetic retinopathy. T he correlations of glutamate and GABA levels with an elevated VEGF lev el provide biochemical support for ischemia-induced neovascularization in patients with PDR. These findings present opportunities for novel therapeutic modalities in the treatment of PDR.