As the central hub of retinal metabolism, mitochondria are vital for sustaining the integrity of the inner blood-retinal barrier (iBRB), which is fundamental to retinal homeostasis. Mitochondrial dysfunction accelerates severe iBRB disruption, a process which is increasingly implicated in a cascade of mitochondrial pathologies including mitochondrial DNA destabilization, oxidative stress, calcium homeostasis disruption, mitochondrial autophagy deficiency, and dysregulated dynamic regulation. This review establishes the iBRB as a crossroads for metabolic, redox, and inflammatory signaling. By analyzing evidence from diabetic retinopathy and retinal vein occlusion models, we clarify how mitochondrial decline translates local energy deficiency into chronic barrier dysfunction. We posit that restoring mitochondrial function is indispensable for vascular resilience and regeneration, a conclusion drawn from integrating molecular, cellular, and translational findings. To advance mitochondrial discoveries into clinical practice, subsequent studies must prioritize achieving spatiotemporally controlled, cell-type-specific interventions with robust in vivo efficacy, thereby successfully translating mitochondrial science into clinical vascular medicine.
Chen et al. (Fri,) studied this question.