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Elevated -Aminobutyric Acid, Glutamate, and Vascular Endothelial Growth Factor Levels in the Vitreous of Patients With Proliferative Diabetic Retinopathy

Jayakrishna Ambati, MD; Kakarla V. Chalam, MD, FRCSC; Dinesh K Chawla, MD; Carl T. D'Angio, MD; Ernest G. Guillet, MD, PhD; Steven J. Rose, MD; Robert E. Vanderlinde, MD; Balamurali K. Ambati, MD

Arch Ophthalmol. 1997;115(9):1161-1166.

Abstract
Objective
To examine the relative levels of -aminobutyric acid (GABA), glutamate, and vascular endothelial growth factor (VEGF) in the vitreous of nondiabetic and diabetic patients.

Methods
Undiluted vitreous samples were obtained from 22 patients with proliferative diabetic retinopathy (PDR) and 28 patients without diabetes who underwent pars plana vitrectomy. Simultaneous venous blood samples also were obtained. Amino acid concentrations were determined using sensitive high-performance liquid chromatography, and VEGF levels by quantitative enzyme-linked immunosorbent assay. Hemoglobin concentrations in the blood and vitreous were determined using spectrophotometry.

Results
The level of GABA in the vitreous of patients with PDR, 29.4±7.8 µmol/L, was significantly higher than in controls (18.4±5.5 µmol/L) (P=.004). The vitreous concentration of glutamate was higher in patients with PDR (24.7±14.0 µmol/L) compared with controls (9.1±5.1 µmol/L) (P<.001). Vitreous VEGF level was significantly higher in patients with 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 presence of PDR. Correcting for possible introduction of these molecules by vitreous hemorrhage did not significantly alter these findings.

Conclusions
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 electroretinographic oscillatory potential abnormalities seen in diabetic retinopathy. The correlations of glutamate and GABA levels with an elevated VEGF level provide biochemical support for ischemia-induced neovascularization in patients with PDR. These findings present opportunities for novel therapeutic modalities in the treatment of PDR.

Author Affiliations
From the Departments of Ophthalmology (Drs J. Ambati, Chawla, Guillet, Rose, and Vanderlinde) and Pediatrics (Dr D'Angio), University of Rochester, Rochester, NY; the Department of Ophthalmology, University of South Carolina, Columbia (Dr Chalam); and the Department of Medicine, Beth Israel Medical Center, New York, NY (Dr B. Ambati).

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