alpha-lipoic acid corrects late-phase supernormal retinal oxygenation response in experimental diabetic retinopathy

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

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.

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.

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.