The brain and eye: Treating cerebral and retinal ischemia through mitochondrial transfer

Stroke remains a devastating disease with limited treatment options, despite our growing understanding of its pathology. While ischemic stroke is traditionally characterized by a blockage of blood flow to the brain, this may coincide with reduced blood circulation to the eye, resulting in retinal ischemia, which may in turn lead to visual impairment. Although effective treatment options for retinal ischemia are similarly scarce, new evidence suggests that deleterious changes to mitochondrial structure and function play a major role in both cerebral and retinal ischemia pathologies. Prior studies establish that astrocytes transfer healthy mitochondria to ischemic neurons following stroke; however, this alone is not enough to significantly mitigate the damage caused by primary and secondary cell death. Thus, stem cell-based regenerative medicine targeting amelioration of ischemia-induced mitochondrial dysfunction via the transfer of functional mitochondria to injured neural cells represents a promising approach to improve stroke outcomes for both cerebral and retinal ischemia. In this review, we evaluate recent laboratory evidence supporting the remedial capabilities of mitochondrial transfer as an innovative stroke treatment. In particular, we examine exogenous stem cell transplants in their potential role as suppliers of healthy mitochondria to neurons, brain endothelial cells, and retinal cells.

Impact statement: Stroke constitutes a global health crisis, yet potent, applicable therapeutic options remain effectively inaccessible for many patients. To this end, stem cell transplants stand as a promising stroke treatment and as an emerging subject of research for cell-based regenerative medicine. This is the first review to synthesize the implications of stem cell-derived mitochondrial transfer in both the brain and the eye. As such, this report carries fresh insight into the commonalities between the two stroke-affected organs. We present the findings of this developing area of research inquiry with the hope that our evaluation may advance the use of stem cell transplants as viable therapeutic alternatives for ischemic stroke and related disorders characterized by mitochondrial dysfunction. Such lab-to-clinic translational advancement has the potential to save and improve the ever increasing millions of lives affected by stroke.