Eye Opener in Stroke

Abstract

Background and Purpose— Retinal ischemia is a major cause of visual impairment in stroke patients, but our incomplete understanding of its pathology may contribute to a lack of effective treatment. Here, we investigated the role of mitochondrial dysfunction in retinal ischemia and probed the potential of mesenchymal stem cells (MSCs) in mitochondrial repair under such pathological condition. Methods— In vivo, rats were subjected to middle cerebral artery occlusion then randomly treated with intravenous MSCs or vehicle. Laser Doppler was used to evaluate the blood flow in the brain and the eye, while immunohistochemical staining assessed cellular degeneration at days 3 and 14 poststroke. In vitro, retinal pigmented epithelium cells were exposed to either oxygen-glucose deprivation or oxygen-glucose deprivation and coculture with MSCs, and subsequently, cell death and mitochondrial function were examined immunocytochemically and with Seahorse analyzer, respectively. Results— Middle cerebral artery occlusion significantly reduced blood flow in the brain and the eye accompanied by mitochondrial dysfunction and ganglion cell death at days 3 and 14 poststroke. Intravenous MSCs elicited mitochondrial repair and improved ganglion cell survival at day 14 poststroke. Oxygen-glucose deprivation similarly induced mitochondrial dysfunction and cell death in retinal pigmented epithelium cells; coculture with MSCs restored mitochondrial respiration, mitochondrial network morphology, and mitochondrial dynamics, which likely attenuated oxygen-glucose deprivation-mediated retinal pigmented epithelium cell death. Conclusions— Retinal ischemia is closely associated with mitochondrial dysfunction, which can be remedied by stem cell-mediated mitochondrial repair.

Stem Cells as Drug-like Biologics for Mitochondrial Repair in Stroke

“…Hemispheric blood flow post-stroke was also reduced [38]. RPE cell death is also increased in the in vitro OGD model [38]. Importantly, ischemic insult and the severe loss of healthy retinal cells coincides with mitochondrial dysfunction in both in vivo and in vitro models.…”

“…On days 3 and 14 following MCAO, immunohistochemical analysis reveals insufficient blood flow to the retina, corresponding to a decrease in retinal ganglion cell survival and an increase in the rate of degeneration of the optic nerve [38]. Hemispheric blood flow post-stroke was also reduced [38]. RPE cell death is also increased in the in vitro OGD model [38].…”

“…It is valuable to understand the role of mitochondrial dysfunction in cerebral and ocular disease post-stroke due to the markedly similar pathology and treatment options between these two conditions [38]. In addition, given the benefits of MSC therapy in restoring mitochondrial function, it is plausible to infer that MSC treatment will have analogous effects in retinal ischemia, potentially diminishing the ischemia-induced cell death [38].…”

“…It is valuable to understand the role of mitochondrial dysfunction in cerebral and ocular disease post-stroke due to the markedly similar pathology and treatment options between these two conditions [38]. In addition, given the benefits of MSC therapy in restoring mitochondrial function, it is plausible to infer that MSC treatment will have analogous effects in retinal ischemia, potentially diminishing the ischemia-induced cell death [38]. The use of a middle cerebral artery occlusion (MCAO) rat model and retinal pigment epithelium (RPE) cell culture model of OGD are beneficial for studying retinal ischemia, as they accurately reproduce the same symptomology in vivo and in vitro, respectively [38].…”

“…However, the perfusion rate stabilizes between the two eyes within three days of stroke, owing to the lack of collateral circulation [43][44][45]. On days 3 and 14 following MCAO, immunohistochemical analysis reveals insufficient blood flow to the retina, corresponding to a decrease in retinal ganglion cell survival and an increase in the rate of degeneration of the optic nerve [38]. Hemispheric blood flow post-stroke was also reduced [38].…”