ArticleJournal of translational medicine2026
Mitochondria transplantation reduces intraocular pressure by improving mitochondrial function and remodeling trabecular meshwork.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMitochondrial transplantation represents a promising therapeutic strategy for diseases characterized by mitochondrial dysfunction, with mitochondrial dysfunction in trabecular meshwork (TM) recognized as a key pathogenic mechanism in primary open-angle glaucoma (POAG) where impairment drives sustained intraocular pressure (IOP) elevation.
objectiveThis study aimed to develop a novel therapeutic approach through direct mitochondria transplantation to replenish mitochondrial quantity in TM cells.
methodsThe healthy mitochondria were isolated from mouse liver tissues, and uptake by TM cells and their ability to alleviate oxidative stress were evaluated under varying oxidative stress conditions, using both 2D monolayers and 3D spheroid models. The underlying mechanisms were explored through proteomic analysis and western blot. The intraocular distribution and therapeutic efficacy, including IOP -lowering effects and TM structural improvement, were assessed in a chronic OHT animal model.
resultsTM cells actively internalized exogenous mitochondria, which were subsequently enriched within the cellular mitochondrial pool. Moderate oxidative damage enhanced this mitochondrial uptake. At both 2D and 3D cellular levels, exogenous mitochondria effectively reduced oxidative stress and enhanced cell viability. This cytoprotective effect was mediated primarily by suppressing excessive mitophagy, thereby restoring autophagic homeostasis and increasing cell survival. In vivo tracking revealed a preferential accumulation of exogenous mitochondria in the TM region, a phenomenon that was more pronounced in the chronic OHT model. A single intracameral injection of mitochondria produced a potent, sustained, and stable reduction in IOP. This therapeutic effect surpassed that of two first-line clinical hypotensive agents (Timolol maleat and Latanoprost eye drops) and was well-tolerated.
conclusionThis research provides the first systematic evidence establishing mitochondrial transplantation as an efficacious anti-glaucoma therapy, proposing innovative IOP-lowering strategies for glaucoma treatment.
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