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-Lipoic Acid Corrects Late-Phase Supernormal Retinal Oxygenation Response in Experimental Diabetic Retinopathy

¹From the Department of Anatomy and Cell Biology, and the ²Kresge Eye Institute, Wayne State University, Detroit, Michigan.

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

METHODS. Retinal oxygenation (PO₂) 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 PO₂.

RESULTS. In control SD rats, PO₂(t₁ – ra) > PO₂(t₂ – t₁) (P < 0.05) was found panretinally. In diabetic SD rats, the superior, but not the inferior, hemiretina had subnormal PO₂(t₁– ra) (P < 0.05) and supernormal PO₂(t₂ – t₁) (P < 0.05). In control LEW rats, PO₂(t₁ – ra) and PO₂(t₂ – t₁) were not significantly different (P > 0.05). Also, control and diabetic LEW rat panretinal PO₂(t₁ – ra) were lower (P < 0.05) than in the respective SD groups. In diabetic LEW rats, a supernormal (P < 0.05) panretinal PO₂(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 PO₂ 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 PO₂.

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