Abstract
Purpose :
Retinal ischemia is a major cause of blindness in the world and to this date few therapeutic options are available. Within cerebral ischemia, the role of vasculature in the acute stage following ischemia has been suggested as a therapeutic target showing both functional improvements and a decrease in neuronal cell death. However within retinal research vascular contractile function has not been prioritized. Previous studies have evaluated the role of endothelin-1 following global cerebral ischemia (Blixt et al 2016) and the role of the MEK/ERK1/2 pathway in the ophthalmic artery in vitro (Blixt et al 2017). However, this study is the first to show how ophthalmic artery contraction can be attenuated in vivo with the MEK/ERK1/2 inhibitor U0126 immediately following a 2 hour ischemic insult via occlusion of the ophthalmic artery.
Methods :
The middle cerebral artery occlusion model was performed with a 2 hour occlusion. Due to the close proximity of the ophthalmic artery to the middle cerebral artery, the right eye was occluded in each rat with the left serving as an internal control. The vascular properties of the ophthalmic artery were evaluated with wire myography while immunohistochemistry coupled with fluorescence microscopy was used to visualize vimentin and GFAP expression in the retina of both control and occluded eyes.
Results :
Results from this study show a glial response in the retina following ischemia, confirming that our method of occlusion elicits damage to the eye. Occlusion of the ophthalmic artery leads to a significant increase in ETB contractility 48 hours after ischemia. Furthermore, U0126 treatment attenuates the observerd endothelin-1-mediated vasoconstriction.
Conclusions :
This is the first study showing an in vivo effect of U0126 on vascular contractility following ischemia. Coupled with the knowledge obtained from cerebral vasculature, these results could point towards a novel therapeutic approach following ischemia related injuries to the eye.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.