Stroke gets in your eyes: stroke-induced retinal ischemia and the potential of stem cell therapy

Abstract

Stroke persists as a global health and economic crisis, yet only two interventions to reduce stroke-induced brain injury exist. In the clinic, many patients who experience an ischemic stroke often further suffer from retinal ischemia, which can inhibit their ability to make a functional recovery and may diminish their overall quality of life. Despite this, no treatments for retinal ischemia have been developed. In both cases, ischemia-induced mitochondrial dysfunction initiates a cell loss cascade and inhibits endogenous brain repair. Stem cells have the ability to transfer healthy and functional mitochondria not only ischemic neurons, but also to similarly endangered retinal cells, replacing their defective mitochondria and thereby reducing cell death. In this review, we encapsulate and assess the relationship between cerebral and retinal ischemia, recent preclinical advancements made using in vitro and in vivo retinal ischemia models, the role of mitochondrial dysfunction in retinal ischemia pathology, and the therapeutic potential of stem cell-mediated mitochondrial transfer. Furthermore, we discuss the pitfalls in classic rodent functional assessments and the potential advantages of laser Doppler as a metric of stroke progression. The studies evaluated in this review highlight stem cell-derived mitochondrial transfer as a novel therapeutic approach to both retinal ischemia and stroke. Furthermore, we posit the immense correlation between cerebral and retinal ischemia as an underserved area of study, warranting exploration with the aim of these treating injuries together.

Keywords

• laser doppler; mcao; mesenchymal stem cells; mitochondrial network; mitochondrial transfer; ophthalmic artery; optic nerve; oxygen-glucose deprivation; regenerative medicine; retinal ganglion cells; visual impairment