iPSC-derived ITGA6-positive cells restore aqueous humor outflow in glaucoma eyes

Decreased trabecular meshwork (TM) cellularity, which is a critical pathological cause of primary open-angle glaucoma (POAG), lacks effective regenerative therapies. Here, we used multi-modal RNA sequencing to investigate regeneration mechanisms of induced pluripotent stem cell-derived TM cells (iPSC-TM). We identified a distinct iPSC-derived alpha6 integrin-positive (iPSC-ITGA6+) cell population with unique transcriptional signatures absent in primary TM cells. Particularly, iPSC-ITGA6+ cells demonstrated superior capacity to induce TM proliferation, restore aqueous humor outflow, and repopulate damaged ocular drainage tissues. Furthermore, we uncovered paraspeckle assembly as the key molecular mechanism enabling rejuvenation of endogenous cells, establishing a novel menRNA-based strategy for TM regeneration.