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Konstantinos Nikolakopoulos, Laura Kowalczuk, Tatiana Favez, Catherine Martin, Francine Behar-Cohen, Jean-Antoine Pournaras; Characterization of a Laser Induced Branch Retinal Vein Occlusion in a Rat Model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3673.
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Anti-VEGF agents are commonly used in the treatment of branch retinal vein occlusion (BRVO). However, the exact mechanism, as well as the reason of possible treatment failure in a number of cases, have not been fully understood yet. Our primary objective is to observe and compare the temporal modifications in the expression of the VEGF family members, and their receptors between normal and BRVO rat retina, in order to establish new targets that will allow improvement of the existing therapies.
By using laser photocoagulation two to three hemi-retinal veins of Long Evans rats (n=35) were occluded. Subsequently, on day 1, 2, 4 and 7 following the occlusion, in vivo and ex vivo analysis were performed in order to characterize the temporal evolution of the morphological and molecular alterations. The in vivo analysis included: eye fundus photography, Optical Coherence Tomography (OCT), and fluo-angiography. Regarding the ex vivo analysis, immunohistochemistry on cryosections and retinal flatmounts, along with Real Time and Quantitative PCR, were performed.
Retinal serous detachments occurred in the totality of the eyes at day 1 along with hemorrhages that gradually resolved throughout the follow-up. Reperfusion of the occluded branch retinal veins initiated on day 4 and continued until day 7, where only two veins of two different eyes remained occluded. Despite reperfusion, ischemia and edema were visible and were limited to the areas dependent on the occluded veins. Neovascularization began as soon as day 2, and peaked on day 4 after laser treatment, in accordance to the activation of the VEGF receptors, Flt-1 and Flt-2. On the contrary, no receptor activation was observed in the non-occluded retina. PlGF-1 was expressed on day 1 in the vessels of the treated hemi-retina, and had a maximum expression on day 7, particularly in the impact zone and the neovascular areas. Flatmounts stained for NG2+ pericytes demonstrated a severe pericyte loss, which led to destabilization of the peripheral capillary network.
Given the early and sustained expression of PlGF-1 in the occluded hemi-retina, particularly in the neovascular membranes, we believe that this could be a potential therapeutic target against neovascular complications in the BRVO
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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