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Norman P Blair, Anthony Felder, Michael Robert Tan, Mahnaz Shahidi; A Rodent Model of Graded Reduction of Retinal Blood Flow for Ischemia Research. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4877.
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© ARVO (1962-2015); The Authors (2016-present)
The retinal injury induced by short-term total ischemia may differ from that induced by longer-term partial ischemia or from that in clinical vascular occlusions which retain some blood flow. Methods are lacking to establish graded levels of retinal blood flow (RBF) for arbitrary durations without compromising the ocular media transparency which is necessary for optical measurement of retinal physiologic parameters during the RBF reductions. We herein present such a method based on the observation that rats with bilateral carotid artery (CA) occlusion survive and have severe retinal abnormalities, whereas with unilateral CA occlusion eyes have minimal abnormalities (Slakter et al. AJO 1984;97:168).
Under anesthesia, one CA was ligated in Long Evans rats (N = 5). A custom-built clamp consisting of a rod mounted on a translational stage and a backstop was positioned to straddle the second CA. By adjusting the rod position relative to the backstop, graded compressions of the CA were achieved. RBF imaging was performed in the ipsilateral eye 10 minutes after CA compressions that varied from 0% (full flow) to 100% (minimal flow). Retinal arterial (DA) and venous (DV) diameters were measured from fundus reflectance images at 532 nm. Venous blood velocity (VBV) was measured from the movement of systemically injected 2 µm fluorescent microspheres. RBF was calculated from DV and VBV. Data were normalized to full flow values and plotted as functions of % CA compression. Data points were fitted to first or second order polynomials.
DA changed minimally with % CA compression, but DV decreased at higher levels of CA compression Both VBV and RBF showed slight changes between 0% and 50% CA compression, but both dropped precipitously at compressions greater than 50% and approached zero at 100% CA compression. Best fit cures described by second order polynomials gave R2 values of 0.78 and 0.65 for VBV and RBF, respectively.
Reductions of RBF were induced and measured during controlled compression of the ipsilateral CA and ligation of the contralateral CA. Substantial, graded reductions in RBF were observed with more than 50% CA compression. This method holds promise for evaluation of retinal ischemic injury induced by controlled, constant, reductions of RBF for variable durations.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
Retinal Blood Flow versus Percent Carotid Artery Compression
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