PMID- 34313929 OWN - NLM STAT- MEDLINE DCOM- 20211026 LR - 20220531 IS - 1573-2630 (Electronic) IS - 0165-5701 (Linking) VI - 41 IP - 11 DP - 2021 Nov TI - MicroRNA-93-5p participates in type 2 diabetic retinopathy through targeting Sirt1. PG - 3837-3848 LID - 10.1007/s10792-021-01953-4 [doi] AB - 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. CI - (c) 2021. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Wang, Hui AU - Wang H AD - Department of Ophthalmology, Shijiazhuang People's Hospital, No. 365, Jianhua South Street, Yuhua District, Shijiazhuang, 050030, Hebei Province, China. FAU - Su, Xian AU - Su X AD - Department of Ophthalmology, Shijiazhuang People's Hospital, No. 365, Jianhua South Street, Yuhua District, Shijiazhuang, 050030, Hebei Province, China. FAU - Zhang, Qian-Qian AU - Zhang QQ AD - Department of Ophthalmology, Shijiazhuang People's Hospital, No. 365, Jianhua South Street, Yuhua District, Shijiazhuang, 050030, Hebei Province, China. FAU - Zhang, Ying-Ying AU - Zhang YY AD - Department of Ophthalmology, Shijiazhuang People's Hospital, No. 365, Jianhua South Street, Yuhua District, Shijiazhuang, 050030, Hebei Province, China. FAU - Chu, Zhan-Ya AU - Chu ZY AD - Department of Ophthalmology, Shijiazhuang People's Hospital, No. 365, Jianhua South Street, Yuhua District, Shijiazhuang, 050030, Hebei Province, China. FAU - Zhang, Jin-Ling AU - Zhang JL AD - Department of Ophthalmology, Shijiazhuang People's Hospital, No. 365, Jianhua South Street, Yuhua District, Shijiazhuang, 050030, Hebei Province, China. FAU - Ren, Qian AU - Ren Q AD - Department of Ophthalmology, Shijiazhuang People's Hospital, No. 365, Jianhua South Street, Yuhua District, Shijiazhuang, 050030, Hebei Province, China. 17603119856@163.com. LA - eng PT - Journal Article DEP - 20210727 PL - Netherlands TA - Int Ophthalmol JT - International ophthalmology JID - 7904294 RN - 0 (MicroRNAs) RN - 0 (Mirn93 microRNA, rat) RN - EC 3.5.1.- (Sirt1 protein, rat) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2/complications/genetics MH - *Diabetic Retinopathy/genetics MH - *MicroRNAs/genetics MH - Rats MH - Sirtuin 1/genetics/metabolism MH - Up-Regulation OTO - NOTNLM OT - Diabetic retinopathy OT - Mir-93-5p OT - Sirt1 OT - T2DM EDAT- 2021/07/28 06:00 MHDA- 2021/10/27 06:00 CRDT- 2021/07/27 12:33 PHST- 2021/02/07 00:00 [received] PHST- 2021/07/09 00:00 [accepted] PHST- 2021/07/28 06:00 [pubmed] PHST- 2021/10/27 06:00 [medline] PHST- 2021/07/27 12:33 [entrez] AID - 10.1007/s10792-021-01953-4 [pii] AID - 10.1007/s10792-021-01953-4 [doi] PST - ppublish SO - Int Ophthalmol. 2021 Nov;41(11):3837-3848. doi: 10.1007/s10792-021-01953-4. Epub 2021 Jul 27.