Prog Retin Eye Res. 2025 Dec 23:101432. doi: 10.1016/j.preteyeres.2025.101432. Online ahead of print.
ABSTRACT
The cornea is the eye’s outermost protective and refractive barrier whose physiological homeostasis depends on mitochondrial competence and dynamic stability. Mitochondrial dysfunctions are characterized by impaired electron transport chain efficiency, excessive reactive oxygen species generation, calcium dysregulation, and disrupted dynamics. Clinically, mitochondrial dysfunctions underlie the pathogenesis of diverse corneal disorders, including Fuchs endothelial corneal dystrophy, dry eye disease, diabetic keratopathy, keratoconus and infectious keratitis. Although prior work has linked mitochondrial dysfunction to corneal pathology, an integrated, mechanism-to-therapy synthesis remains limited. Dysregulated mitochondrial redox signaling exacerbates oxidative stress and the release of mitochondrial-derived damage-associated molecular patterns, triggering inflammatory cascades and cell death pathways. Imbalances in mitochondrial metabolism and dynamics further amplify cellular damage and disease progression. This review systematically delineates mitochondria’s roles in corneal energy supply and homeostatic regulation, clarifies the causal involvement of mitochondrial dysfunction and dysregulated networks in corneal disease pathogenesis. More importantly, by elucidating the intricate mechanisms of mitochondrial regulation and dysfunction, this review underscores the transformative potential of mitochondria-targeted interventions in advancing corneal disease management and improving clinical outcome.
PMID:41448387 | DOI:10.1016/j.preteyeres.2025.101432