Downregulation of SIRT6 and NMNAT2 is associated with proliferative diabetic retinopathy

Abstract

Purpose

To determine the expression levels of SIRT6 and NMNAT2 in diabetic retinopathy (DR).

Methods

We obtained peripheral blood mononuclear cells (PBMCs) and vitreous samples from 77 patients with type 2 diabetes mellitus: 52 with DR and 25 without DR, and 27 healthy control subjects. Western blot analysis and qRT-PCR were performed to evaluate the expression of SIRT6 and NMNAT2 in their PBMCs. The levels of IL-1β, IL-6, and TNF-α in the vitreous fluid were determined by ELISA. Immunohistochemistry was performed to detect the expression of SIRT6 and NMNAT2 in proliferative DR (PDR) and the control subjects.

Results

The expression of SIRT6 and NMNAT2 was markedly downregulated in DR patients, which was negatively correlated with the increased expression of IL-1β, IL-6 and TNF-α. Additionally, we observed decreased expression of SIRT6 and NMNAT2 in the fibrovascular membranes of PDR patients.

Conclusions

The downregulated expression of SIRT6 and NMNAT2 in PDR patients reveals a potential pathogenic association; more extended studies could verify them as potential therapeutic targets.