An hypothesis to account for the renewal of outer segments in rod and cone photoreceptor cells: renewal as a surrogate antioxidant.

It is undisputed that glutathione (GSH) is an important cellular antioxidant. Although it is commonly believed that GSH is present in all retinal cells, several publications show that GSH is not immunologically detectable in outer segments of rod and cone photoreceptor cells, but is present in inner retinal cells and the pigment epithelium. Using these intriguing and surprising findings as a starting point, an hypothesis is proposed that the renewal of outer segments serves as a surrogate antioxidant for GSH and that the exceptional vulnerability of photoreceptor cells to certain toxic chemicals is linked to the deficiency in GSH in outer segments as a reductant, a detoxicant, and as an enzymatic cofactor.

Nuclear magnetic resonance and biochemical measurements of glucose utilization in the cone-dominant ground squirrel retina.

Purpose: To provide quantitative information on glucose utilization in cone-dominant ground squirrel retinas.

Methods: Ground squirrel eyecups were incubated in medium containing (14)C-glucose, and the production of (14)CO(2) was measured. Measurements were also made of lactic acid production (glycolysis).

Blockade of PARP activity attenuates poly(ADP-ribosyl)ation but offers only partial neuroprotection against NMDA-induced cell death in the rat retina.

Recent reports have linked neuronal cell death by necrosis to poly(ADP-ribose) polymerase-1 (PARP-1) hyperactivation. It is believed that under stress, the activity of this enzyme is up-regulated, resulting in extensive poly(ADP-ribosyl)ation of nuclear proteins, using NAD(+) as its substrate, which, in turn, leads to the depletion of NAD(+). In efforts to restore the level of NAD(+), depletion of ATP occurs, resulting in the shutdown of ATP-dependent ionic pumps.

Reexamining the hyperglycemic pseudohypoxia hypothesis of diabetic oculopathy.

Purpose: To test the hypothesis that diabetes alters retinal NAD+-to-NADH ratios early in the course of the disease (e.g., the hyperglycemic pseudohypoxia hypothesis).

Cultured retinal neuronal cells and Müller cells both show net production of lactate.

Glucose has long been considered the substrate for energy metabolism in the retina. Recently, an alternative hypothesis (metabolic coupling) suggested that mitochondria in retinal neurons utilize preferentially the lactate produced specifically by Müller cells, the principal glial cell in the retina. These two views of retinal metabolism were examined using confluent cultures of photoreceptor cells, Müller cells, ganglion cells, and retinal pigment epithelial cells incubated in modified Dulbecco's minimal essential medium containing glucose or glucose and lactate.

Effects of L-glutamate/D-aspartate and monensin on lactic acid production in retina and cultured retinal Müller cells.

We have investigated the dependence of the rate of lactic acid production on the rate of Na(+) entry in cultured transformed rat Müller cells and in normal and dystrophic (RCS) rat retinas that lack photoreceptors. To modulate the rate of Na(+) entry, two approaches were employed: (i) the addition of L-glutamate (D-aspartate) to stimulate coupled uptake of Na(+) and the amino acid; and (ii) the addition of monensin to enhance Na(+) exchange. Müller cells produced lactate aerobically and anaerobically at high rates.

Metabolic mapping in mammalian retina: a biochemical and 3H-2-deoxyglucose autoradiographic study.

It has long been known that mammalian retinas metabolize glucose aerobically to lactic acid and carbon dioxide. The classical view holds that glucose is the primary substrate for energy metabolism in all retinal cells, and that photoreceptor cells have the highest rates of glycolysis and respiration. A different and more recent view is that the Müller cells are the principal, if not sole aerobic producers of lactate, which then serves as the primary fuel for the mitochondria in photoreceptor cells and other retinal neurons.

Hyperosmolarity and electroretinogram (ERG) potentials in isolated rat retinas: possible implications in diabetic models.

In this report, the effects of increases in the osmolarity of media superfusing isolated rat retinas on the a-wave, b-wave and oscillatory potentials of the electroretinogram (ERG) were examined. Osmolarity of the media was raised from 310 milliosmoles (control) to 340 and 370 milliosmoles by addition of NaCl or sucrose. Increases in osmolarity led to rapid decreases in the amplitudes of the b-wave and oscillatory potentials with little change in the amplitude of the a-wave.

Modulation of the Pasteur effect in retinal cells: implications for understanding compensatory metabolic mechanisms.

The purpose of the present experiments was to enhance understanding of the factors that are critical for the survival of retinal cells exposed to mitochondrial inhibition. Confluent cultures of Müller cells (rMC-1) and human retinal pigment epithelial cells (hRPE) were incubated in Dulbecco's minimal essential medium in the presence and absence of 1x10(-5)M Antimycin A, an inhibitor of mitochondrial electron transport. To modulate the rates of aerobic and anaerobic glycolysis, cells were incubated in media containing varying concentrations of glucose and 1-100 micro M of iodoacetic acid (IAA), an inhibitor of glyceraldehdye-3-phosphate dehydrogenase (G3PDH).