Experimental Study On Laser Photocoagulation Induced Choroidal Neovascularization Of Rhesus Monkey Is Inhibited By Humanized Anti-VEGF Fusion Protein

Purpose:Choroidal neovascularization(CNV) is a common pathological process in many retinal diseases,which is a degenerative change can be occur in a variety of eye diseases such as AMD, pathologic myopia, eventually lead to serious irreversible vision loss. Therefore, building a CNV animal model more closer to our human beings and exploring a new way anti-CNV for the prevention and treatment is of great significance. We construct a new experimental choroidal neovascularization model of monkey, then observe of inhibition of CNV by humanized anti-VEGF fusion protein in our research.Methods:1. Establishment of an animal model of choroidal neovacularization1.1 Experimental monkey model of CNV: use 8 ordinary healthy adult rhesus monkeys, under general anesthesia,every 8 burns were performed in a circular fashion with 532 nm laser. The approximate laser parameters were as follows:spot size, 50μm; laser power, 0.4W; and exposure time, 0.1 second. Then complete the establishment of the CNV model.1.2 20 days after laser photocoagulation, color fundus photography, fluorescein angiography and optical coherence tomography were used to detect and measure the extent and evidence of leakage of CNV.2. Humanized anti-VEGF fusion protein inhibit CNV in vivo test of rhesus monkey2.1 20 days after laser photocoagulation, we randomly divided these 8 rhesus monkeys into 4 groups:the control group(NS), low dose group(100μg), sino-dose group(300μg), and high dose group(500μg). All the study group eyes were administrated intravitreal injection of different doses of the test compounds.2.2 Color fundus photography, fluorescein angiography, optical coherence tomography were performed on 2w, 4w after laser to detect if any bleeding in fundus, the size of CNV and the change of CNV leakage.2.3 According to FFA results, with statistical method, use special computer software to analysis the size of CNV leakage.2.4 Using optical coherence tomography to detect the existence of CNV and the inhibition of humanized anti-VEGF fusion protein.2.5 4 weeks after the administration, kill the monkeys, take the eye balls, being embedded,slicing and HE staining, then observe the macular changes. Results:1. 20 days after laser, fibrous tissue proliferation appeared visible in color fundus photographs; FFA shew fluorescein leakage at the early stage, formed high fluorescein mass at the late stage. Optical coherence tomography findings also shew a typical performance, can be seen high densiy red-and-white stripes, few can be seen shallow retinal detachment.2. 2 weeks after intravitreal injection of humanized anti-VEGF fusion protein, there were no significant change in low dose group( P>0.05), sino-dose group and high dose group can all reduce the fluorescein leakage of choroidal neovascularization, but the effect between those two groups had no significance statistically(P<0.05). And 4 weeks after intravitreal injection, compared with the control group, among different groups the leakage caused by choroidal neovascularization all reduced, especially with the high dose, the reduction of leakage was the most obvious one.Conclusion:We constructed the experimental choroidal neovascularization model by 532 nm laser successfully within high power. Intravitreal injection of humanized anti-VEGF fusion protein can effectively inhibit the development of choroidal neovascularization.