Exploring the role of Müller cells-derived exosomes in diabetic retinopathy.

Autor: Gad MS; Eye Research Institute, Oakland University, Rochester, MI 48309-4479, USA; Eye Research Center (OUWB)/ERC, William Beaumont School of Medicine, Royal Oak, MI 48309-4479, USA; Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Egypt. Electronic address: Mohamedshalabey@mans.edu.eg., Elsherbiny NM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. Electronic address: nelsherbiny@ut.edu.sa., El-Bassouny DR; Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Egypt. Electronic address: refat_dalia@hotmail.com., Omar NM; Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Egypt. Electronic address: nesrinemoustafa@mans.edu.eg., Mahmoud SM; Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Egypt. Electronic address: Safi_mn@mans.edu.eg., Al-Shabrawey M; Eye Research Institute, Oakland University, Rochester, MI 48309-4479, USA; Eye Research Center (OUWB)/ERC, William Beaumont School of Medicine, Royal Oak, MI 48309-4479, USA. Electronic address: malshabrawey@oakland.edu., Tawfik A; Eye Research Institute, Oakland University, Rochester, MI 48309-4479, USA; Eye Research Center (OUWB)/ERC, William Beaumont School of Medicine, Royal Oak, MI 48309-4479, USA. Electronic address: amtawfik@oakland.edu.
Jazyk: angličtina
Zdroj: Microvascular research [Microvasc Res] 2024 Jul; Vol. 154, pp. 104695. Date of Electronic Publication: 2024 May 08.
DOI: 10.1016/j.mvr.2024.104695
Abstrakt: Exosomes are nanosized vesicles that have been reported as cargo-delivering vehicles between cells. Müller cells play a crucial role in the pathogenesis of diabetic retinopathy (DR). Activated Müller cells in the diabetic retina mediate disruption of barrier integrity and neovascularization. Endothelial cells constitute the inner blood-retinal barrier (BRB). Herein, we aim to evaluate the effect of Müller cell-derived exosomes on endothelial cell viability and barrier function under normal and hyperglycemic conditions. Müller cell-derived exosomes were isolated and characterized using Western blotting, nanoparticle tracking, and electron microscopy. The uptake of Müller cells-derived exosomes by the human retinal endothelial cells (HRECs) was monitored by labeling exosomes with PKH67. Endothelial cell vitality after treatment by exosomes under normo- and hypoglycemic conditions was checked by MTT assay and Western blot for apoptotic proteins. The barrier function of HRECs was evaluated by analysis of ZO-1 and transcellular electrical resistance (TER) using ECIS. Additionally, intracellular Ca +2 in HRECs was assessed by spectrofluorimetry. Analysis of the isolated exosomes showed a non-significant change in the number of exosomes isolated from both normal and hyperglycemic condition media, however, the average size of exosomes isolated from the hyperglycemic group showed a significant rise when compared to that of the normoglycemic group. Müller cells derived exosomes from hyperglycemic condition media markedly reduced HRECs cell count, increased caspase-3 and Annexin V, decreased ZO-1 levels and TER, and increased intracellular Ca + when compared to other groups. However, treatment of HRECs under hyperglycemia with normo-glycemic Müller cells-derived exosomes significantly decreased cell death, preserved cellular integrity and barrier function, and reduced intracellular Ca +2 . Collectively, Müller cell-derived exosomes play a remarkable role in the pathological changes associated with hyperglycemia-induced inner barrier dysfunction in DR. Further in vivo research will help in understanding the role of exosomes as therapeutic targets and/or delivery systems for DR.
Competing Interests: Declaration of competing interest the authors declare no conflicts of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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