Research Foundation of State University Brooklyn United States
Blast mediated injuries from Improvised Explosive Devices are strongly associated with severe ocular morbidity and visual impairment and are the leading cause of combat-related injuries. In this study, we documented both in vivo microvascular dysfunction in the retina as a function of a blast, but also explored the effects of a therapeutic intervention to haltreserve the degeneration. To that extent, we use 48 mice split into three cohorts related to how long after the blast 7 days, one month or four months they were studied and a control group of 16. Our hypothesis is that when arterial flow is pathologically reduced, for example by ocular injury, the flow in the downstream capillary beds is reduced uniformly. We tested this hypothesis with Confocal Laser Endomicroscopy CLE in vivo imaging to examine the blood flow through the arteriolar vessels and into capillary beds. We also identified mural cells such as pericytes, which have the ultimate active control point for blood flow and regulate non-uniform blood flow in capillary beds. Dysfunctional mural cell-driven non-uniform blood flow can then lead to cell death due to the failure of local oxygenation gradients within the capillary bed. Our hypothesis concerning the mechanistic pathway of action of nitric oxide precursors i.e. L-Arginine is that they improve capillary blood flow and prevent ischemiahypoxia by dilating arterioles and microvessels that would otherwise vasospasm or restrict due to TOI. CLE revealed a significantly different vasospasm rate among cohorts, which are postulated as deriving from mural cell dysfunction in TOI.