Downregulation of SIRT6 and NMNAT2 is associated with proliferative diabetic retinopathy

Mol Vis. 2023 Oct 2:29:160-168. eCollection 2023.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2* / complications
  • Diabetic Retinopathy* / genetics
  • Diabetic Retinopathy* / metabolism
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Nicotinamide-Nucleotide Adenylyltransferase* / genetics
  • Nicotinamide-Nucleotide Adenylyltransferase* / metabolism
  • Sirtuins* / genetics
  • Sirtuins* / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • Interleukin-6
  • Nicotinamide-Nucleotide Adenylyltransferase
  • NMNAT2 protein, human
  • SIRT6 protein, human
  • Sirtuins
  • Tumor Necrosis Factor-alpha