EFFECT OF TOCOTRIENOL-RICH FRACTION ON THE VISUAL-BEHAVIOUR RESPONSE OF RATS WITH STREPTOZOTOCIN-INDUCED DIABETIC RETINOPATHY

Abstract

Diabetic retinopathy (DR) is the second leading diabetic complication, which impairs vision. Tocotrienol-rich fraction (TRF) has shown to protect against diabetes-induced retinal oxidative stress. Therefore, we investigate TRF effect on the visual-behaviour response in rats with streptozotocin (STZ)-induced DR. Male Sprague-Dawley rats (200-250 grams) were divided into diabetic received intraperitoneal 55mg/kg STZ and normal (N) rats received citrate buffer. Diabetic rats were subdivided to diabetic-vehicle (DV) and diabetic-TRF (DT). N and DV received vehicle, whereas DT received 100 mg/kg TRF orally for 12 weeks. The general behaviour in open field arena was assessed at week 12 followed by visual-behaviour response, a mirror and reversed mirror was added.  Retinal tissues were collected for haematoxylin and eosin (H&E) staining. In open field, N showed higher zone crossings (3.73-folds, p<0.001), travelling (2.02-folds, p<0.001), rearing (2.22-folds, p<0.001) and grooming (4.33-folds, p<0.01) with lower freezing (2.47-folds, p<0.001) and faecal pellet (4.17-folds, p<0.01) versus DV. Compared to DV, general behaviour in DT was similar to N.  N spent more time with higher zone entries toward mirrored compared to non-mirrored and reversed mirror zones (p<0.05 and p<0.01 respectively).  N also showed higher freezing within mirrored zone versus DV (2.00-folds, p<0.05). Visual-behaviour response in DT was comparable to N.  Retinal morphometry showed reduction in cell count in ganglion cell layer and layer thickness in DV versus N (p<0.01). In DT these parameters were greater than DV (p<0.05), which correlated with visual-behaviour response. Hence, orally administered TRF improves visual-behaviour response in DR rodent model associated with retinal morphology preservation.

Acknowledgement: This work was supported by Universiti Teknologi MARA (UiTM) grants (600-IRMI/DANA 5/3/BESTARI (P) (001/2018) and 600-IRMI/DANA 5/3/BESTARI (P) (012/2018)) and Ministry of Education (MOE), MY grant (600-IRMI/FRGS 5/3 (101/2019)).