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The Effects Of Intravitreous Bevacizumab On Angiogenesis In A BN Rat Model Of Laser-Induced Choroidal Neovascularization.

Posted on:2009-08-15Degree:MasterType:Thesis
Country:ChinaCandidate:J YuFull Text:PDF
GTID:2144360272459111Subject:Ophthalmology
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Choroidal neovascularization(CNV) is the main reason for severe sight loss of patients with age-related macular degeneration and myopia.Several studies have showed that intravitreous bevacizumab could induce regression of CNV.However, many patients didn't have their sight improvement last long enough after intravitreously admission of bevacizumab.So far,the only study to evaluate the effects of intravitreous bevacizumab on angiogenesis was based on an rabbit model in which choroidal neovascularization was induced by VEGF165.Thus,neither the pathology of the CNV,nor the rabbit fundus vessel system shares something in common with CNV developed in human.As a result,it couldn't modeling the exact influence of intravitreous bevacizumab on angiogenesis of CNV in human eyes.The purpose of our study is to investigate the inhibitory effects of intravitreous bevacizumab on angiogenesis in a BN rat model of laser-induced choroidal neovascularization,which shares many charactors with CNV developed in human.Part 1 Study on the experimental model of diode laser-induced choroidal neovascularization in the BN ratsObjective To evaluate the feasibility of diode laser-induced choroidal neovascularization(CNV) model in the Brown Norway rats in order to establish the foundation for the development of treatment for CNV.Methods Experimental eyes in 24 rats were received a series of 8 diode laser(561nm) lesions per eye(120Mw,100μm,0.1s) around optic disc.Fundus fluorescein angiography(FFA) and indocyanine green angiography(ICGA) were performed,then the rats were sacrificed immediately,the eyes were enucleated and processed for histopathologic examination on days3,7,14,21,28,35,56 after laser photocoagulation..Results ICGA showed CNV first appeared on day 3 after photocoagulation,and well-developed on day 14.On day 14,disciform leakage staining appeared in the FFA, and the score of fluorescein staining maitained stable from day 14 to 28.CNV was ascertained by light microscopy on day 14.No significant progress of the thickness of laser-induced CNV occurred from day 14 to day 28.(P>0.05). Conclusions The present studies demonstrated that diode laser photocoagulation could be used to produce choroidal neovascularization experimental model in the Brown Norway rat.CNV can be induced rapidly by the method,persists for a long period.Part 2The Effects of Intravitreous Bevacizumab on Angiogenesis in a BN Rat Model of Laser-Induced Choroidal Neovascularization.Objective To investigate the inhibitory effects of intravitreous bevacizumab on angiogenesis in a BN rat model of laser-induced choroidal neovascularization.Methods 12 male BN rats,who had one eye photocoagulated by diode laser to induce CNV,were randomly divided into control group and bevacizumab group.The rats in the bevacizumab group(6 eyes) received 2μl AvastinTM intravitreally at the same time of photocoagulated,while the control group(6 eyes) received 2μl BSS as vehicle. Follow-up evaluations continued for 21d and included fundus fluorescein angiography(FFA) and ICGA.Enucleated eyes were processed for hematoxylin and eosin(H&E) staining and immunohistochemistry staining for VEGF.Results ICGA showed CNV developed,similarly,both in the bevacizumab group and the control group on day 7.But the scores of fluorescein staining at that time were significantly lower in the bevacizumab group.However,the scores soon increased till day 21,but still lower than those of the control group.On day 21,the mean thickness of CNV was significantly reduced in the bevacizumab group.And the CNV in the bevacizumab group were negative for VEGF according to the result of immmuohistochemistry staining.Conclusions Early intravitreous injection of bevacizumab can inhibit the development of CNV both in morphology and permeability in the BN rat model. However,bevacizumab could neither block the formation of CNV,nor suppress the leakage permanently.Thus,combined therapy with bevacizumab may be more potential to treat CNV effectively.
Keywords/Search Tags:Choroidal neovascularization, Antibodies,monoclonal, Angiogenesis inhibitors, Indocyanine green angiography, Rat, BN
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