Hepatic Satellite Cell Activation and Alteration of Vitamin A Status Are Relevant to the Aggravation of Retinopathy by T2DM.

Abstract

Purpose: Type 2 diabetes mellitus (T2DM) leads to diabetic retinopathy (DR) and hepatic impairments. The potential mutual interaction and the intermediator between these two injuries are not well elucidated. Both the retina and liver are involved in vitamin A metabolism, suggesting a potential involvement of vitamin A and its metabolites in this mutual interaction. This study aimed to elucidate the impact of either DR or hepatic impairment on the pathogenesis and vitamin A status of each during injury progression.

Methods: A streptozotocin (STZ)-high-fat diet (HFD)-induced T2DM rodent model was applied to examine via electroretinography (ERG) retinal and hepatic histopathology at 0, 12, 16, 20, 24, 28, and 30 weeks after T2DM induction. The levels of retinol in the retina, liver, serum, all-trans-retinal in the retina, and retinyl palmitate in the liver were measured at various time points after T2DM induction.

Results: Retinal dysfunction, evidenced by reduced ERG responses, appeared at week 12, followed by photoreceptor and ganglion cell damage after the 16th week. Hepatic impairments began with hepatic stellate cell activation and decreased retinyl palmitate storage, concurrent with reduced retinal retinol and increased all-trans-retinal. Serum retinol levels remained stable, but reductions in transthyretin (TTR) and retinol-binding protein 4 (RBP4) were found, likely disrupting vitamin A transport in the serum.

Conclusions: These results provide novel insights into hepatic injury and vitamin A status, implicating both in the aggravation of retinopathy under the influence of T2DM. The current results may raise clinical awareness on hepatic issues and vitamin A involvement during DR progression.