Abstract
Purpose:
Experimental models of Retinal Vein Occlusions (RVO) are limited and temporal microvascular alterations have not yet been fully elucidated. Our aim was to develop a rodent model which faithfully creates ischemic RVO and characterize the natural progression of microvascular changes associated with vein occlusion.
Methods:
RVO was performed by focal laser photocoagulation in anesthetized adult male C57Bl/6J mice (n=43) following intraperitoneal administration of fluorescein. Multiple argon laser spots (power 80mW, spot size 50μm, 0.5 sec duration) were placed on retinal veins of the left eye to stop blood flow. The right eye served as an unlasered control. Fluorescein angiograms and OCT images were acquired immediately following occlusion and repeated at day 1, 3, 7, 14 or 28. Ischemic areas on angiograms were quantified using ImageJ. Following sacrifice, the eyes were enucleated for detailed morphological evaluation.
Results:
Complete vein occlusion was associated with venous dilation upstream of the occlusion site and constriction of the downstream vein. There was also evidence of reverse venous blood flow and leakage from vessels in the deep vascular plexus of the retina. Spontaneous reperfusion occurred in 50% of mice by day 3 and complete recanalization of the occluded vein was observed in 90% of mice by day 7. Occlusion of one vein did not result in ischemia due to vascular remodeling by dilated and tortuous venous collaterals. However, when two or more veins were occluded, an area of non-perfusion could be observed 7 days after induction of RVO, where perfused capillary beds were significantly reduced from 37.1±6.6% to 11.8±8.8% (mean±SD) in the laser-occluded retinas (P<0.0001, unpaired t test).
Conclusions:
Occlusion of a single retinal vein is not sufficient to induce ischemia due to dilation of venous collaterals. Multiple adjacent veins need to be occluded to generate a measurable area of ischemia. Ultimately this model will allow evaluation of responses to retinal ischemia in the adult eye and enable assessment of remodeling responses and development of novel therapies for ischemic retinopathies.
Keywords: 572 ischemia •
578 laser •
551 imaging/image analysis: non-clinical