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article · Biomedicine & Pharmacotherapy

Effect of bone marrow mesenchymal stem cells-derived exosomes on diabetes-induced retinal injury: Implication of Wnt/ b-catenin signaling pathway

202247 citationsOpen accessBadr University in Cairo

In plain language

Diabetic retinopathy is a severe complication of diabetes that damages the retina. Researchers examined whether exosomes derived from bone marrow mesenchymal stem cells could protect against diabetes-induced retinal injury by targeting the Wnt/beta-catenin signalling pathway. Using a rat model divided into six experimental groups, the investigation evaluated retinal tissues through imaging, histopathology, and molecular analysis of markers linked to oxidative stress, inflammation, and blood vessel formation. Treatment with these stem cell-derived exosomes inhibited the Wnt/beta-catenin pathway and reversed diabetes-related retinal damage. The therapy increased antioxidant enzymes while decreasing oxidant levels, inflammatory molecules, and abnormal blood vessel growth markers. Furthermore, the exosomes countered retinal harm triggered by Wnt3a activation. Overall, the findings demonstrate that bone marrow mesenchymal stem cell exosomes reduce retinal injury in diabetic models by dampening Wnt/beta-catenin signalling, providing biological evidence for cell-free therapeutic strategies.

Key takeaways

  • Bone marrow mesenchymal stem cell exosomes significantly reduced signs of diabetic retinopathy in a rat model.
  • The exosome treatment blocked the Wnt/beta-catenin signalling pathway and counteracted Wnt3a-induced retinal injury.
  • Exosome administration lowered retinal oxidants, increased antioxidant enzymes, and suppressed markers of inflammation and angiogenesis.

Why it matters

Diabetic retinopathy is a leading cause of vision loss in people living with diabetes. While whole stem cells offer therapeutic potential, cell-free alternatives such as exosomes could provide similar healing benefits with fewer biological complexities. Demonstrating that exosomes can reduce inflammation, oxidative stress, and tissue damage in animal models provides a vital step toward safer treatments for diabetic eye complications.

Commercialisation angle

This research represents early-stage, preclinical animal research into cell-free biologics for diabetic retinopathy. The findings could inform future therapeutic development by pharmaceutical and biotechnology companies developing treatments for diabetic retinal complications. However, because the study is limited to laboratory rats, extensive further preclinical testing, formulation development, and human clinical trials will be necessary before any real-world clinical application can be realised.

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Abstract

BACKGROUND: Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus. Mesenchymal stem cells are currently studied as therapeutic strategy for management of DR. Exosomes, considered as a promising cell-free therapy option, display biological functions similar to those of their parent cells. In retinal development, Wnt/b-catenin signaling provides key cues for functional progression. The present study aimed to evaluate the potential efficacy of bone marrow-derived mesenchymal stem cell-derived exosomes (BM-MSCs-Ex) in diabetes-induced retinal injury via modulation of the Wnt/ b-catenin signaling pathway. METHODS: Eighty-one rats were allocated into 6 groups (control, DR, DR + DKK1, DR + exosomes, DR + Wnt3a and DR + exosomes+Wnt3a). Evaluation of each group was via histopathological examination, assessment of gene and/or protein expression concerned with oxidative stress (SOD1, SOD2, Nox2, Nox4, iNOS), inflammation (TNF-α, ICAM-1, NF-κB) and angiogenesis (VEGF, VE-cadherin). RESULTS: Results demonstrated that exosomes blocked the wnt/b-catenin pathway in diabetic retina concomitant with significant reduction of features of DR as shown by downregulation of retinal oxidants, upregulation of antioxidant enzymes, suppression of retinal inflammatory and angiogenic markers. These results were further confirmed by histopathological results, fundus examination and optical coherence tomography. Additionally, exosomes ameliorative effects abrogated wnt3a-triggered retinal injury in DR. CONCLUSION: Collectively, these data demonstrated that exosomes ameliorated diabetes-induced retinal injury via suppressing Wnt/ b-catenin signaling with subsequent reduction of oxidative stress, inflammation and angiogenesis.

Research topics

  • Retinal Diseases and Treatments
  • Extracellular vesicles in disease
  • Ocular Diseases and Behçet’s Syndrome

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DOI: 10.1016/j.biopha.2022.113554

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