MicroRNA-93-5p participates in type 2 diabetic retinopathy through targeting Sirt1

• Published in: International ophthalmology 2021-11, Vol.41 (11), p.3837-3848
• Main Authors: Wang, Hui, Su, Xian, Zhang, Qian-Qian, Zhang, Ying-Ying, Chu, Zhan-Ya, Zhang, Jin-Ling, Ren, Qian
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Blood vessels; Bovine serum albumin; Capillaries; Cytokines; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetic retinopathy; Diabetic Retinopathy - genetics; Fluorescein; Fluorescein isothiocyanate; Indicators; Inflammation; Medicine; Medicine & Public Health; MicroRNAs - genetics; miRNA; Ophthalmology; Original Paper; Oxidative stress; Permeability; Rats; Reporter gene; Retina; Retinopathy; Serum albumin; SIRT1 protein; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Trypsin; Up-Regulation; Vascular endothelial growth factor; Western blotting
• ISSN: 0165-5701; 1573-2630
• DOI: 10.1007/s10792-021-01953-4

Objective To investigate the role of miR-93-5p in rats with type 2 diabetic retinopathy (DR) through targeting Sirt1. Methods The targeting correlation between miR-93-5p and Sirt1 was validated by dual-luciferase reporter gene assay. Type 2 diabetes mellitus (T2DM) rat models were received intravitreal injection of antagomir NC (negative control), miR-93-5p antagomir, miR-93-5p agomir and/or recombinant Sirt1, followed by observation of pathological changes in retina via HE staining. Besides, retinal vascular permeability was determined by fluorescein isothiocyanate-bovine serum albumin (FITC-BSA), while the retinal vasculature was observed through retinal trypsin digestion. Expression of miR-93-5p and Sirt1 was measured by qRT-PCR and Western blotting, while the levels of VEGF, proinflammatory cytokines and anti-oxidative indicators were determined using corresponding kits. Results MiR-93-5p could target Sirt1 as analyzed by the luciferase reporter gene assay. Rats in the T2DM group presented the up-regulation of miR-93-5p and down-regulation of Sirt1 in the retina, and miR-93-5p inhibition could up-regulate Sirt1 expression in the T2DM rats. Recombinant Sirt1 decreased retinal vascular permeability and acellular capillaries with improved pathological changes in retina from T2DM rats, which was abolished by miR-93-5p agomir. Moreover, miR-93-5p inhibition or Sirt1 overexpression decreased the levels of VEGF and proinflammatory cytokines while enhancing the activity of anti-oxidative indicators. However, indicators above had no significant differences between T2DM group and T2DM + agomir + Sirt1 group. Conclusion MiR-93-5p, via targeting Sirt1, could affect the vascular permeability and acellular capillaries and mitigate the inflammation and oxidative stress in the retinas, which may play a critical role in DR.