Retinal Ischemia in the In Vivo Rodent: Cellular and Vascular Characteristics

Abstract

Retinal vessel occlusion is among the leading causes of vision loss. The functional and cellular effects of acute loss of blood flow have not been investigated fully, and current treatments only address secondary complications of ischemic damage. This work has developed new tools with which to investigate retinal blood flow and glial Ca2+ signaling in health and disease. Retinal blood flow in the rat was examined by using an imaging technique known as laser speckle flowmetry (LSF) to generate two dimensional maps of blood flow changes. We demonstrated that the inner retinal and choroidal circulations could be imaged noninvasively, and used this technique to study functional hyperemia responses in the retina. We discovered that blood flow increases were more difficult to evoke in areas away from primary arterioles, suggesting that capillary regulation of functional hyperemia is unlikely. To determine the role of glial Ca2+ signaling on neurovascular coupling, we developed a method of injecting Ca2+ indicator dyes and caged Ca2+ compounds into the vitreous, near the retinal surface. This study demonstrated that glial Ca2+ signaling plays a role in retinal blood flow regulation. Finally, using a variety of imaging tools, including LSF, we discovered that retinal spreading depression (RSD) is evoked by acute retinal ischemia. RSD in the in vivo, vascular retina has never previously been seen. Spreading depression in the cortex has been shown to play a role in expanding brain injuries. Our observation of RSD is an important finding that carries exciting clinical implications and may be a promising therapeutic target for preventing vision loss after retinal ischemia.