Reexamining the hyperglycemic pseudohypoxia hypothesis of diabetic oculopathy.
OBJECTIVE
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).


METHODS
In freshly excised age-matched control and diabetic rat retinas, measurements were made of the NAD+ and NADH content as well as a surrogate marker of NAD+-to-NADH ratios obtained from lactate and pyruvate levels. In addition, the effect of various hyperglycemic levels was assessed from measurements of retinal lactate and pyruvate concentrations and the rate of lactic acid production in vitro (isolated rat retinas, monolayer cultures of human retinal pigment epithelial cells, and rabbit lens epithelial cells).


RESULTS
No significant differences (P>0.05) were found between control and diabetic tissues in their amount of total NAD+ and NADH/retina, and the ratio of NAD+ to NADH, or in their content of lactate, pyruvate, and adenosine triphosphate (ATP) or in the ratio of lactate to pyruvate. The content of lactate and pyruvate in retinas incubated for 2 hours in media containing 10 or 30 mM glucose was the same as found in fresh tissues, but the levels of these metabolites in retinas incubated in media containing 5 mM glucose declined in comparison to the fresh values. There were no significant differences in lactate content in cultured retinal and lens cells that were exposed to 5 or 30 mM glucose-containing media.


CONCLUSIONS
The present results do not support the hyperglycemic pseudohypoxia hypothesis of diabetic retinopathy.
Diederen
Roselie M H
RM
Department of Ophthalmology, University Hospital Maastricht, Maastricht, The Netherlands.
Starnes
Catherine A
CA
Berkowitz
Bruce A
BA
Winkler
Barry S
BS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000449:Aldehyde Reductase / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003930:Diabetic Retinopathy / Q000209:etiology* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology; D009243:NAD / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism
D009243:NAD; D019344:Lactic Acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D000449:Aldehyde Reductase; D005947:Glucose