alpha-lipoic acid corrects late-phase supernormal retinal oxygenation response in experimental diabetic retinopathy.
OBJECTIVE
To test the hypothesis that preventative alpha-lipoic acid (LPA) treatment corrects an abnormal retinal oxygenation response in experimental diabetic retinopathy.


METHODS
Retinal oxygenation (DeltaPO2) was measured by MRI before (room air [ra]) and during a 4-minute carbogen inhalation challenge in five groups: control Sprague-Dawley (SD) and Lewis (LEW) rats, 3- to 4-month diabetic SD and LEW rats, and 4-month diabetic LEW rats preventatively treated with a chow LPA admix (400 mg/kg per chow). Comparisons were made between the initial 2 minutes of oxygenation change (measured using ra and first carbogen periods [t1 - ra]) and the next 2-minute change (assessed with first and second carbogen periods [t2-t1]) for superior and inferior hemiretinal DeltaPO2.


RESULTS
In control SD rats, DeltaPO2(t1-ra) > DeltaPO2(t2-t1) (P <0.05) was found panretinally. In diabetic SD rats, the superior, but not the inferior, hemiretina had subnormal DeltaPO2(t1- ra) (P < 0.05) and supernormal DeltaPO2(t2-t1) (P < 0.05). In control LEW rats, DeltaPO2(t1-ra) and DeltaPO2(t2-t1) were not significantly different (P > 0.05). Also, control and diabetic LEW rat panretinal DeltaPO2(t1-ra) were lower (P < 0.05) than in the respective SD groups. In diabetic LEW rats, a supernormal (P < 0.05) panretinal DeltaPO2(t2-t1) was found that could be corrected with preventative LPA treatment.


CONCLUSIONS
These data support the hypothesis and suggest that the influence of strain differences on the interpretation of retinovascular DeltaPO2 as a surrogate of drug treatment efficacy for diabetic retinopathy may be minimized by measuring a late-phase supernormal response. The LPA data raise the possibility that oxidative stress contributes to diabetes-induced supernormal DeltaPO2.
Roberts
Robin
R
Department of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA.
Luan
Hongmei
H
Berkowitz
Bruce A
BA
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002245:Carbon Dioxide / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism; D018496:Hyperoxia / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D018384:Oxidative Stress; D010100:Oxygen / Q000008:administration & dosage / Q000378:metabolism*; D010101:Oxygen Consumption; D010313:Partial Pressure; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D008063:Thioctic Acid / Q000627:therapeutic use*
D000975:Antioxidants; D002245:Carbon Dioxide; D008063:Thioctic Acid; C011700:carbogen; D010100:Oxygen