RVO is the second most common cause of blindness after diabetic retinopathy amongst young adults and current therapeutics do not prevent sustained chronic vision loss. To study cell-specific roles of the components of the NVU in the context of neurovascular injury, we used a characterized mouse model of Retinal Vein Occlusion (RVO). Non-invasive in vivo visualization and manipulation of the NVU can be done in the retina. Parsing out the roles of specific cell types in pathology associated with retinal neurovascular injuries can help identify new therapeutic targets. While molecular signatures involved in retinal vascular pathology have been identified, the specific contribution of the injured endothelium and reactive gliosis to vision dysfunction and neuronal death remain to be established. Disruption of the NVU results in the breakdown of the blood-retinal barrier (BRB), edema, inflammation, retinal neuronal atrophy, and visual dysfunction. Neurovascular injuries damage the communication between endothelial, pericytes, glial, and neuronal cells that form the neurovascular unit (NVU). Neurovascular hypoxic-ischemic injuries in the retina are a leading cause of degenerative vision loss characterized by impairment of the retinal vasculature through aberrant neovascularization and decreased blood flow. These findings reveal specific endothelial and astroglial non-apoptotic caspase-9 roles in inflammation and neurovascular injury respectively and concomitant relevancy to contrast sensitivity decline. Lastly, we discovered that Astro Casp9 contributes to capillary ischemia and contrast sensitivity decline after RVO (P-RVO). One of the noted glial changes was increased levels of astroglial cl-caspase-6, which we found to be activated cell intrinsically by astroglial caspase-9 (Astro Casp9). We found that EC Casp9 is implicated in contrast sensitivity decline, induction of inflammatory cytokines, and glial reactivity. In this study, we aimed to explore the role of EC Casp9 in vision loss and inflammation.

Using this model, we previously discovered that after vascular damage, there was non-apoptotic activation of endothelial caspase-9 (EC Casp9) knock-out of EC Casp9 led to a decrease in retinal edema, capillary ischemia, and neuronal death. To understand the mechanisms that contribute to neuronal death, we use a mouse model of retinal vein occlusion (RVO). Neurovascular injuries damage homeostatic communication between endothelial, pericyte, glial, and neuronal cells through signaling pathways that remain to be established. Retinal neurovascular injuries are a leading cause of vision loss in young adults presenting unmet therapeutic needs.

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