The Investigation Of Treating Macular Edema Secondary To Retinal Vein Occlusion By Conbercept

Background and purpose: Retinal vein occlusion(RVO)is one of the most common retinal vascular diseases.RVO can cause retinal hemorrhage and macular edema,causing decreased vision.In recent years,the number of RVO patients in China is increasing year by year,the treatment of RVO-related macular edema is still not ideal.In the past few years,ophthalmologists have used anti-VEGF antibodies,such as bevacizumab and ranibizumab,as standard treatments for RVO.The main reason is that VEGF can participate in the formation of new blood vessels,VEGF has an effect of increasing vascular permeability.According to recent randomized clinical trial data,Conbercept has been used in the treatment of RVO in China with satisfactory therapeutic effects.In this experiment,we studied the therapeutic effect of Conbercept on RVO.The beneficial effect of Conbercept is mainly due to its anti-VEGF effect.Conbercept can inhibit retinal angiogenesis and reduce vascular permeability in the retina.In addition to the involvement of VEGF in the pathogenesis of RVO,studies have shown that inflammation and oxidative stress are also involved in the pathological process of RVO secondary to macular edema.The accumulation of inflammatory mediators and anaerobic free radicals leads to the expression of VEGF.Current treatments for RVO and its complications,macular edema and neovascularization,including laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor(VEGF),have shown that Conbercept can be used to treat RVO.However,the specific mechanism is still unclear.This study explores the mechanism of the effect of Conbercept on the treatment of RVO secondary macular edema,and provides a scientific basis for the future treatment of RVO.Methods:Part 1: Effect of Conbercept on retinal morphology,angiogenesis,oxidative stress and related inflammatory factors in patients with RVO secondary macular edema.The study was conducted from April 1,2017 to June 31,2018.Forty patients with BRVO secondary to macular edema who were consecutively treated in the Third People's Hospital of Dalian,20 of whom were treated with intravitreal injection of Conbercept.Before and after intravitreal injection of Conbercept,OCTA,the patient's retinal vascular density and FAZ area were measured.This part of the study was a prospective study with duration of 4 months;after the patient's consent,patients in the Conbercept treatment group were treated with intravitreal injection of Conbercept at the beginning of the study,and patients were treated every month.Conbercept injection,treatment lasted for 3 months;patient aqueous humor was taken during surgery;and optical coherence tomography angiography(OCTA)and fundus fluorescein angiography(FFA)were performed on RVO patients before and after surgery.The retinal blood vessel morphology,retinal blood flow area,vascular density and the area of the foveal avascular area(FAZ)were observed.The ELISA kit was used to detect the inflammation-related factors in the aqueous humor of each group.ICAM-1,MIP-1 and prostaglandin-related factors PGE1,PGE2 and PGFtherapeutic mechanism of Conbercept;GSH kit was used to detect the content of GSH in the aqueous humor of each group to determine Conbercept Therapeutic effect on RVO and the antioxidant effect of Conbercept.Part 2: Effects of Conbercept on retinal morphology,angiogenesis,cell proliferation,oxidative stress and related inflammatory cytokine expression in RVO mice.This study used 7-week-old male C57BL/6J mice as subjects.The RVO model of the bengal rose red was injected into the tail vein of the mice,and the Campbell was injected intravitreally into the RVO mice once a month for 3 months.Some mouse eyeballs were dehydrated and embedded,paraffin sectioned;H&E staining was used to observe the changes of mouse eyeball morphology;frozen sections were prepared from partial eyeballs of each group of mice,and the expression of reactive oxygen species in mouse eyeballs was observed by DHE staining;Ice staining of the eyeball tissue of each group was used to stain the heterologous agglutinin B4 to observe the proliferation of retinal endothelial cells,thereby confirming the effect of Conbercept on retinal neovascularization in mice;by optical coherence tomography angiography(OCTA)The retinal microvascular changes in mice were observed,and the effects of injection of Conbercept on the retina morphology were observed.Western blot was used to detect vascular endothelial growth factor(VEGF),inflammation-related factors ICAM-1,MIP-1 and prostaglandin.Factor expression;and further determine the effect of Conbercept on the expression of NOX-1 and NOX-4 in the oxidative stress pathway.The expression of oxidative stress related genes NOX-1 and NOX-4 in the eyeball tissues of each group was examined by real-time quantitative PCR.Results:In the first part,we observed the changes of retinal and macular area in each group by OCTA.The results showed that the retina of RVO patients was thickened obviously,the macular area was obviously edematous,and some patients had bleeding in the retina.After treatment with Conbercept These phenomena were significantly alleviated;by measuring the levels of reduced glutathione(GSH)in the aqueous humor of each group of patients,the results showed that the level of GSH in the aqueous humor of patients with RVO was significantly lower than that of the control group,after Conbercept After treatment,the level of GSH in the aqueous humor of RVO patients was restored,indicating that Conbercept has certain anti-oxidation effect;the inflammation-related factors ICAM-1,MIP-1 and prostaglandins in the aqueous humor of each group were determined by ELISA.The expression of related factors showed that Conbercept can reduce the expression of inflammation-related factors ICAM-1 and MIP-1,but did not affect the expression of prostaglandin-related factors in aqueous humor.The mechanism needs further investigation.The H&E staining results in the second part showed that by injecting the RVO model of the Bengal red structure mouse,the retina of the model mouse was found to have obvious bleeding points in the retina of the model group,and the macular area of the mouse retina was obvious.Edema,and the retinal inner plexus(IPL)and inner nuclear layer(INL)of RVO mice were significantly thickened.After treatment with RBC mice by injection of Conbercept,the pathological changes of mouse retina were significantly relieved;the results showed that the retinal endothelial cells of the RVO model group were significantly proliferated compared with the control group.The proliferation of mouse retinal endothelial cells was weakened after treatment with Conbercept.This also explains that Conbercept can slow the proliferation of retinal endothelial cells in RVO mice and reduce the formation of retinal neovascularization;DHE results show that the level of ROS in the retina of RVO mice is significantly higher than that of the control group.After treatment with Conbercept,the level of retinal ROS in mice was significantly reduced,indicating that Conbercept may have antioxidant effects;Furthermore,the expressions of oxidative stress-related proteins NOX-1 and NOX-4 were further detected.The expressions of NOX-1 and NOX-4 in RVO mouse eyeballs were significantly higher than those in the control group.After treatment with Conbercept,the expression of NOX-1 and NOX-4 in the eyeball of RVO mice was significantly down regulated.To confirm the anti-oxidation effect of Conbercept,the expression of NOX-1 and NOX-4 in mouse eyeballs was detected by real-time quantitative PCR.The results again confirmed the antioxidant effects of Conbercept;By detecting the protein expression of inflammation-related factors ICAM-1,MIP-1 and prostaglandin-related factors,The results showed that Conbercept significantly reduced the expression of ICAM-1 and MIP-1 induced by RVO,but Conbercept did not affect the expression of prostaglandin-related factors,and its specific mechanism still needs further investigation.Conclusion: Conbercept can be used for the treatment of RVO;Conbercept has anti-inflammatory and anti-oxidant effects;Conbercept can partially inhibit the levels of ICAM-1 and MIP-1,but for the levels of PGE1,PGE2,PGFeffect.