Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma

• Published in: Advanced science Vol. 11; no. 32; pp. e2309307 - n/a
• Main Authors: Li, Tong, Zhang, Wen‐Meng, Wang, Jie, Liu, Bai‐Jing, Gao, Qiao, Zhang, Jing, Qian, Hai‐Dong, Pan, Jun‐Yi, Liu, Ming, Huang, Qing, Fang, Ai‐Wu, Zhang, Qi, Gong, Xian‐Hui, Cui, Ren‐Zhe, Liang, Yuan‐Bo, Lu, Qin‐Kang, Wu, Wen‐Can, Chi, Zai‐Long
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.08.2024; John Wiley and Sons Inc; Wiley
• Subjects: Biomarkers; engineered sEVs; Extracellular vesicles; Glaucoma; MicroRNAs; miR‐29; Patients; Pharmacists; Plasma; plasma‐derived sEVs; RGCs degeneration; RGCs degeneration; engineered sEVs; plasma‐derived sEVs; miR‐29; glaucoma
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202309307

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma‐derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV‐miR‐29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR‐29s in RGC pathophysiology. It is showed that the overexpression of miR‐29b‐3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR‐29b‐3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV‐miR‐29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV‐based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases. Plasma‐derived small extracellular vesicles (sEVs) from glaucoma patients (Gla‐PDEV) alleviate optic nerve injury. Elevated levels of PDEV‐miR‐29s are associated with the progression of glaucoma. The delivery of miR‐29b‐3p by engineered sEVs protects retinal ganglion cells (RGCs). PDEV may be involved in the systemic regulation respond to glaucomous neurodegeneration. PDEV‐miR‐29s are potential biomarkers and promising therapeutic agents for glaucoma.