Decreased retinal blood flow in experimental colitis; improvement by eye drop administration of losartan

Abstract

Patients with inflammatory bowel disease suffer not only from gut inflammation, but also from extraintestinal manifestations of the disease, including ocular pathology. The mechanisms causing ocular inflammation in these patients are unknown. The purpose of the current study was to investigate the possible vascular changes occurring in the retina using a mouse model of acute colitis, that is, ingestion of dextran sodium sulfate (DSS). Intravital microscopy of anesthetized mice revealed that DSS caused a significant 30-40% decrease in retinal red blood cell velocities, and a 45% decrease in total retinal blood flow, but no changes in intraocular pressure. To determine whether the decreases in retinal perfusion could be inhibited by an angiotensin II receptor antagonist, losartan was administered by eye drops in a subset of the mice prior to the intravital microscopy measurements. Topical losartan was able to largely attenuate the altered hemodynamics induced by DSS. We conclude that angiotensin II might be a possible target for reducing the vascular changes occurring distantly in the eye during colitis.

Imaging Single–Cell Blood Flow in the Smallest to Largest Vessels in the Living Retina

“…However, the diameters reported by intravital microscopy studies (Harris et al, 2013; Lee & Harris, 2008; Z. Wang et al, 2010, 2011; Watts et al, 2013; Wright & Harris, 2008; Wright et al, 2009, 2012; Yadav & Harris, 2011) for the same vessel class are at least a factor of two greater than our values. Mean velocities for the same vessels are also similarly higher in these studies compared to our measured values.…”

“…To the best of our knowledge, we have counted all of fifteen journal papers which measure retinal blood velocity and/or flow in the living mouse eye (Blair et al, 2016; Harris, Watts, & Leskova, 2013; Lee & Harris, 2008; Liu et al, 2017; Muir, Rentería, & Duong, 2012; Z. Wang, Yadav, Leskova, & Harris, 2010, 2011; Watts, Eshaq, Carter, & Harris, 2013; Wright & Harris, 2008; Wright, Messina, & Harris, 2009; Wright, Singh Yadav, McElhatten, & Harris, 2012; Yadav & Harris, 2011; Zawadzki et al, 2015; Zhi et al, 2014, 2012). As stated earlier, all of these studies measure velocity/flow only in the primary (first generation) vessels emerging from the optic disk.…”

“…As stated earlier, all of these studies measure velocity/flow only in the primary (first generation) vessels emerging from the optic disk. Studies with objectively reportable values are summarized in Table 1, except for (Watts et al, 2013). A graphical summary, classified by imaging technique, is given in Figure 11.…”

“…For mean velocities in primary vessels, some studies used fluorescent microspheres or labelled RBCs (Harris et al, 2013; Lee & Harris, 2008; Z. Wang et al, 2010, 2011; Watts et al, 2013; Wright et al, 2009, 2012; Yadav & Harris, 2011), with 10–30 measurements from sparse fluorescent streaks pooled to average out effects of pulsatile and cross–sectional profile variability. The sparse and too few measurements have the potential to under or overestimate the true mean velocity, by either being biased towards particular cardiac phases, or if the incompressible microspheres travel in preferred radial locations in the vessel lumen.…”

Evaluation of iris functional capillary density in experimental local and systemic inflammation

“…Standard therapies include steroidal and nonsteroidal anti-inflammatery medication. Uveitis is associated with impairments of microvascular blood flow (Demeler, 1979;Watts et al, 2013). Therefore, improvement of the ocular microcirculation is a potential target for uveitis treatment.…”