Restoring Bioenergetics in the Traumatized Eye: The Emergence of Mitochondrial Implantation as a Treatment for Acute Ocular Injury
Emma Peveri, Daniella Beiner, Andrew J. W. Huang, Jian-Xing Ma, Amish Asthana, Anthony Atala, Giuseppe Orlando, Yuanyuan ZhangAcute ocular injuries—such as chemical burns, ischemic insults, and mechanical trauma—frequently lead to irreversible vision loss by triggering rapid intracellular adenosine triphosphate (ATP) depletion, mitochondrial calcium overload, severe oxidative stress, and profound mitochondrial dysfunction. Current clinical management primarily focuses on suppressing inflammation and preventing secondary infection, but it fails to address the underlying bioenergetic collapse that drives cellular degeneration. While stem cell and extracellular vesicle therapies have been widely investigated, direct mitochondrial transplantation has recently emerged as a novel strategy for metabolic rescue. This review evaluates the therapeutic potential of exogenously administered mitochondria to mitigate mitochondrial dysfunction and acute trauma in the eye. Emerging preclinical studies demonstrate that transplanted mitochondria can be internalized by selected ocular cell types, conferring short-term cytoprotection, preserving retinal ganglion cell viability, and accelerating corneal epithelial repair. However, robust evidence regarding long-term mitochondrial integration, functional fusion, durable metabolic rescue, and clinical efficacy remains limited. Despite critical challenges in delivery, stability, and dosing, mitochondrial transplantation represents a promising frontier in regenerative ophthalmology that directly targets bioenergetic failure to preserve vision.