EFFICACY OF TREATMENT AFTER MEASURABLE DIABETICLIKE RETINOPATHY IN GALACTOSE-FED RATS

Purpose. To determine whether the diabeticlike retinal microangiopathi es of the galactose-fed rat model could be ameliorated if intervention by withdrawal of the galactose diet or treatment with the aldose redu ctase inhibitor AL-3152 was initiated after quantifiable microangiopat hies had occurred. Methods. Weanling male Sprague-Dawley rats were ran domized into five groups and fed for up to 24 months Purina laboratory chow (#5001) plus 50% starch (control [CON]), 50% D-galactose (galact ose [GAL]), 50% D-galactose with AL-3152 (approximately 14 mg/kg per d ay) (prevention [PRV]), 50% D-galactose for 6 months followed by inter vention with the inhibitor (intervention [INT]), or 50% D-galactose fo r 6 months followed by replacement with the 50% starch diet (withdrawa l [CWD]). In rats on experimental diets and killed after 6, 18, and 24 months, one retina was prepared for transmission electron microscopy; the other was used for vessel wholemounts using elastase digestion, C apillary images were analyzed by computer morphometry. Results. At 6 m onths, the GAL rats exhibited statistically significant (P < 0.05) inc reases over CON rats in mean capillary basement membrane thickness, ca pillary density, and dilated channels. These parameters tended to incr ease with time in most groups, and the differences between GAL and age -matched CON rats were maintained at the 18- and 24-month endpoints. A lthough the microangiopathies were ameliorated by AL-3152 treatment fr om the onset (PRV) I intervention after 6 months of galactosemia with either galactose withdrawal (GWD) or addition of inhibitor (INT) showe d amelioration in only some parameters at 18 months and no statistical ly significant benefit at the 24-month endpoint. Conclusions. Ameliora tion of galactose-induced retinal microangiopathies with AL-3152 in th e prevention group suggests an efficacious application of aldose reduc tase inhibitors in treating diabetic retinopathy, provided treatment c an begin soon after the onset of diabetes. Intervention after some of the earliest microscopic lesions neither halted progression of the ang iopathy nor provided appreciable benefit at the 24-month follow-up.