Adipose-derived stem cell exosomes alleviate oxidative damage and reduce intraocular pressure in primary open-angle...

This study aimed to investigate the therapeutic effect and underlying mechanism of adipose-derived stem cell exosomes (ADSC-Exos) on oxidative injury in trabecular meshwork (TM) cells of primary open-angle glaucoma (POAG).

In vitro, human TM cells (HTMCs) were exposed to hydrogen peroxide (H₂O₂) to establish an oxidative damage model. In vivo, an Ad5.myocilinY437H mouse model of POAG was constructed. Western blotting, immunofluorescence, reactive oxygen species (ROS) detection, transmission electron microscopy (TEM), Cell Counting Kit-8 (CCK-8) and intraocular pressure (IOP) monitoring were performed to evaluate the intervention effects of ADSC-Exos and the activation of the PI3K/AKT pathway.

Compared with the PBS group, ADSC-Exos significantly increased the phosphorylation levels of PI3K and AKT, reduced intracellular ROS accumulation, and decreased laminin expression in HTMCs (P < 0.05). In the Ad5-MYOC^Y437H-EGFP mice group, day 30 IOP reached 15.2 ± 4.1 mmHg, representing a significant increase over day 0 values (8.7 ± 1.9 mmHg, n = 16, P < 0.001). Furthermore, these eyes exhibited significantly higher IOP compared to the Ad5-EGFP controls (11.0 ± 1.9 mmHg, n = 16, P < 0.05). From day 15 onwards, the IOP in the Ad5-MYOC^Y437H-EGFP + ADSC-Exos group progressively declined, showing a significant difference from the PBS-injected group (11.63 ± 2.6 vs. 15.84 ± 1.6 mmHg, n = 10, P < 0.001). This downward trajectory continued, resulting in a significant IOP difference by day 30 (11.19 ± 2.3 vs. 16.93 ± 3.04 mmHg, P < 0.0001).

ADSC-Exos can alleviate TM oxidative damage, reduce extracellular matrix deposition, and effectively decrease IOP in POAG via the ROS-mediated PI3K/AKT pathway, providing a potential therapeutic strategy for POAG.