School of Medicine, Nankai University, Tianjin, China; Nankai University Affiliated Eye Hospital, Tianjin, China.
Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Vision Science, Tianjin Eye Institute, Tianjin, China.
Invest Ophthalmol Vis Sci. 2024 Jun 3;65(6):16. doi: 10.1167/iovs.65.6.16.
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.
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.
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.
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.
导致角膜混浊的角膜损伤（CI）仍然是一个临床挑战。骨髓间充质干细胞（BMSCs）衍生的外泌体（Exos）已被证明在修复各种组织损伤方面非常有效，并且由于其生物特性，也被认为是极好的药物载体。最近，miR-29b（miR-29b）在自噬调控中发挥了重要作用，该调控与细胞炎症和纤维化有关。然而，miR-29b 和自噬对 CI 的影响尚不清楚。为了找到更好的 CI 治疗方法，我们使用 Exos 携带 miR-29b，并研究其在治疗 CI 中的作用。
用 miR-29b-3p 激动剂/拮抗剂和阴性对照（NCs）转染 BMSCs，以获得 Exos-29b-ago、Exos-29b-anta 和 Exos-NC。对接受 CI 手术的 C57BL/6J 小鼠进行 Exos-29b-ago、Exos-29b-anta、Exos-NC 或 PBS 处理。通过裂隙灯、苏木精和伊红（H&E）染色、免疫荧光、RT-qPCR 和 Western blot 评估角膜的自噬、炎症和纤维化。还研究了 miR-29b-3p 对永生化人角膜上皮细胞（iHCECs）中自噬和炎症的影响。
与 PBS 相比，Exos-29b-ago、Exos-29b-anta 和 Exos-NC 均可改善角膜炎症和纤维化。然而，Exos-29b-ago 通过抑制 PI3K/AKT/mTOR 通路大量积累 miR-29b-3p，进而通过 mTOR/NF-κB/IL-1β 通路抑制角膜炎症，从而发挥出优异的功效。经 Exos-29b-ago 处理后，与其他组相比，III 型胶原、α-平滑肌肌动蛋白、纤维连接蛋白和波形蛋白的表达明显降低。此外，miR-29b-3p 的过表达可防止 iHCECs 发生自噬损伤和炎症损伤。
携带 miR-29b-3p 的 BMSCs 衍生的 Exos 可通过激活自噬，进一步抑制角膜炎症和纤维化，显著改善 CI 的治疗效果。
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