Gabapentin Attenuates Oxidative Stress and Apoptosis in the Diabetic Rat Retina.

Neurodegeneration in diabetic retina has been widely considered as initiating factor that may lead to vascular damage, the classical hallmark of diabetic retinopathy. Diabetes induced altered glutamate metabolism in the retina, especially through glutamate excitotoxicity might play a major role in the neurodegeneration. Increased level of branched chain amino acids (BCAAs) measured in diabetic retina might cause an increase in the neurotoxic level of glutamate by transamination of citric acid cycle intermediates.

Molecular basis for increased lactate formation in the Müller glial cells of retina.

Müller glial cells are highly metabolic active cells that compensate for the high energy demand of retinal neurons. It has been believed that glucose provides the energy needs by the complete oxidation within Müller cells. However, numerous studies indicated that glial cells convert the majority of glucose to lactate, which may serve as an energy source for neurons.

Regulation of glutamate metabolism by hydrocortisone and branched chain keto acids in cultured rat retinal Müller cells (TR-MUL).

Glutamate released from retinal neurons during neurotransmission is taken up by retinal Müller cells, where much of the amino acid is subsequently amidated to glutamine or transaminated to α-ketoglutarate for oxidation. Müller cell glutamate levels may have to be carefully maintained at fairly low concentrations to avoid excesses of glutamate in extracellular spaces of the retina that would otherwise cause excitotoxicity. We employed a cultured rat retinal Müller cell line in order to study the metabolism and the role of Müller cell specific enzymes on the glutamate disposal pathways.

Influence of insulin on glutamine synthetase in the Müller glial cells of retina.

Glutamine synthetase (GS), a Müller cell specific enzyme in the retina, is the key enzyme involve in glutamate metabolism. The goal of this study was to investigate the expression and regulation of GS by insulin in the cultured rat retinal Müller cells. Immunocytochemical and immunoblotting experiments showed that the cultured Müller cells express GS protein under normal cell culture conditions.

The influence of diabetes on glutamate metabolism in retinas.

Excised retinas from euglycemic and diabetic Sprague-Dawley rats were studied to evaluate differences in glutamate metabolism related to diabetes. Reports suggest, neuronal cell death possibly caused by glutamate excitotoxicity, is an early consequence of diabetes. To monitor the influence of diabetes on glutamate metabolism, we measured glutamatergic neurotransmission, anaplerotic glutamate synthesis from (14) CO(2) and pyruvate as well as rates of glutamate cataplerosis ([U-(14) C]glutamate to (14) CO(2) and (14) C-pyruvate).