RRC ID 80966
Author Liu J, Gao J, Lu P, Wang Y, Xing S, Yan Y, Han R, Hao P, Li X.
Title Mesenchymal Stem Cell-Derived Exosomes as Drug Carriers for Delivering miRNA-29b to Ameliorate Inflammation in Corneal Injury Via Activating Autophagy.
Journal Invest Ophthalmol Vis Sci
Abstract PURPOSE:Corneal injury (CI) resulting in corneal opacity remains a clinical challenge. Exosomes (Exos) derived from bone marrow mesenchymal stem cells (BMSCs) have been proven effective in repairing various tissue injuries and are also considered excellent drug carriers due to their biological properties. Recently, microRNA-29b (miR-29b) was found to play an important role in the autophagy regulation which correlates with cell inflammation and fibrosis. However, the effects of miR-29b and autophagy on CI remain unclear. To find better treatments for CI, we used Exos to carry miR-29b and investigated its effects in the treatment of CI.
METHODS:BMSCs were transfected with miR-29b-3p agomir/antagomir and negative controls (NCs) to obtain Exos-29b-ago, Exos-29b-anta, and Exos-NC. C57BL/6J mice that underwent CI surgeries were treated with Exos-29b-ago, Exos-29b-anta, Exos-NC, or PBS. The autophagy, inflammation, and fibrosis of the cornea were estimated by slit-lamp, hematoxylin and eosin (H&E) staining, immunofluorescence, RT‒qPCR, and Western blot. The effects of miR-29b-3p on autophagy and inflammation in immortalized human corneal epithelial cells (iHCECs) were also investigated.
RESULTS:Compared to PBS, Exos-29b-ago, Exos-29b-anta, and Exos-NC all could ameliorate corneal inflammation and fibrosis. However, Exos-29b-ago, which accumulated a large amount of miR-29b-3p, exerted excellent potency via autophagy activation by inhibiting the PI3K/AKT/mTOR pathway and further inhibited corneal inflammation via the mTOR/NF-κB/IL-1β pathway. After Exos-29b-ago treatment, the expressions of collagen type III, α-smooth muscle actin, fibronectin, and vimentin were significantly decreased than in other groups. In addition, overexpression of miR-29b-3p prevented iHCECs from autophagy impairment and inflammatory injury.
CONCLUSIONS:Exos from BMSCs carrying miR-29b-3p can significantly improve the therapeutic effect on CI via activating autophagy and further inhibiting corneal inflammation and fibrosis.
Volume 65(6)
Pages 16
Published 2024-6-3
DOI 10.1167/iovs.65.6.16
PII 2793739
PMID 38856990
PMC PMC11166224
MeSH Animals Autophagy* Blotting, Western Cells, Cultured Corneal Injuries* / genetics Corneal Injuries* / metabolism Corneal Injuries* / therapy Disease Models, Animal* Drug Carriers Exosomes* / metabolism Exosomes* / transplantation Humans Inflammation / metabolism Male Mesenchymal Stem Cells* / metabolism Mice Mice, Inbred C57BL* MicroRNAs* / genetics
Human and Animal Cells HCE-T(RCB1384)