Probucol Protects early-stage diabetic retinopathy through upregulating Nrf2.

Abstract

Purpose : Diabetic retinopathy (DR) is a major microvascular complication of diabetes. This study investigated the therapeutic effect of probucol in a mouse model of diabetic retinopathy.

Methods : C57BL/6 mice were rendered diabetic through Streptozotocin (STZ) intraperitoneal injection. Mice were treated with Probucol or vehicle (DMSO) for 12 weeks. Optical coherence tomography (OCT), Fundus photography (FP) and fundus fluorescein angiography (FFA) were conducted to evaluate retinal structure and damage. Eyes were collected for histology, tunel and Western Blot.

Results : All mice developed hyperglycemia following STZ injection. FFA showed enhanced arterial reflex and beaded vein dilatation in diabetic mice compared with non-diabetic controls and OCT detected reduced inner and middle retinal thickness. Histological analysis uncovered a lower nuclei number and showed slight TUNEL-positive cells in diabetic retina compared to control non-diabetic retina. Probucol treatment prevented diabetes-induced lesions. The treatment also upregulated Nrf2 expression in diabetic retina.

Conclusions : Probucol attenuated diabetes induced retinal degeneration via upregulating the Nrf2 signaling pathway. Probucol may be re-purposed for DR management.

This is a 2020 ARVO Annual Meeting abstract.

 

Spectral domain optical coherence tomography (SD-OCT) examination revealed in vivo retinal alterations in C57BL/6 mice.

 

Ocular histological analysis examination of the effects of probucol on streptozotocin (STZ)-induced diabetic retinopathy in C57BL/6 mice.