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Updated: Jul 5, 2025
Characterization of a Novel Human Organotypic Retinal Culture Technique
Published on: June 9, 2021
Downregulation of SIRT6 and NMNAT2 is associated with proliferative diabetic retinopathy
Hui Chen1, Xiongze Zhang1, Nanying Liao1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
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.
Insights
Sirtuin 6 (SIRT6) and NAD+ N-methyltransferase 2 (NMNAT2) levels are decreased in diabetic retinopathy (DR). This downregulation correlates with increased inflammation and suggests potential therapeutic targets for DR.
Area of Science:
- Ophthalmology
- Endocrinology
- Molecular Biology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss.
- Inflammation plays a critical role in DR pathogenesis.
- Sirtuins and NAD+ metabolizing enzymes are implicated in metabolic and inflammatory diseases.
Purpose of the Study:
- To investigate the expression levels of SIRT6 and NMNAT2 in patients with diabetic retinopathy.
- To explore the correlation between SIRT6 and NMNAT2 expression and inflammatory markers in DR.
- To assess the presence of SIRT6 and NMNAT2 in fibrovascular membranes of proliferative DR (PDR).
Main Methods:
- Collected peripheral blood mononuclear cells (PBMCs) and vitreous samples from type 2 diabetes mellitus patients with and without DR, and healthy controls.
- Quantified SIRT6 and NMNAT2 expression in PBMCs using Western blot and qRT-PCR.
- Measured vitreous levels of IL-1β, IL-6, and TNF-α via ELISA and assessed protein expression in PDR tissues using immunohistochemistry.
Main Results:
- SIRT6 and NMNAT2 expression were significantly downregulated in DR patients compared to controls.
- Downregulated SIRT6 and NMNAT2 levels negatively correlated with increased vitreous levels of IL-1β, IL-6, and TNF-α.
- Reduced expression of SIRT6 and NMNAT2 was observed in the fibrovascular membranes of PDR patients.
Conclusions:
- Downregulated SIRT6 and NMNAT2 expression in PDR suggests a potential pathogenic role in the disease.
- These findings highlight SIRT6 and NMNAT2 as potential therapeutic targets for diabetic retinopathy.
- Further research is warranted to validate their therapeutic potential.
