The therapeutic effect of anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) was determined by a number of factors. Comprehensive thorough analysis of clinical features, imaging results and treatment response can predict the potential efficacy and possible vision recovery for the patient, and also can optimize the treatment regime to make a personalized therapy plan. Precise medicine with data from genomics, proteomics and metabolomics study will provide more objective and accurate biology basis for individual precise treatment. The future research should focus on comprehensive assessment of factors affecting the efficacy of anti-VEGF therapy, to achieve individualized precise diagnosis and treatment, to improve the therapeutic outcome of nAMD.
For choroidal neovascularization (CNV) secondary to pathological myopia, intravitreal injection of anti-VEGF has been widely used in clinic and achieved good outcome. However, due to the differences in the demographic characteristics, stages of disease progression and treatment procedure of CNV, the prognosis of the disease is variable. Complete ellipsoid band, smaller baseline choroidal neovascularization and better baseline vision are important predictors of good outcome of anti-vascular endothelial growth factor treatment. Chorioretinal atrophy or complications related to pathologic myopia indicate a poor prognosis. The influence of age, race, previous photodynamic therapy and early treatment on the prognosis of treatment need to be further studied.
Objective To detect expression of NF-κB in the inner retina and in vestigate the inhibitoryeffect of pyrrolidine dithiocarbamate on retinal neovascularization in rats. Methods The rat models with retinopathy were set up un der the hypoxia condition, and fluorescein fundus angiography (FFA) was used to observe the retinal neovascularization. The expressions of NF-κB in the inner retina in rats with and without neovascularization were detected by immunohisto chemical method. PDTC was intraperitoneally injected in rats with neovascularization to observe the expression of NF-κB in the inner retina and the effect on retinal neovascularization. Results Hypoxia induced NF-κB activation in the retinal glial cells and endothelial cells. But immuno-staining intensity for NF-κB and adhesion molecules were reduced by PDTC intraperitoneal injection. Retin al angiogenesis in rats were suppressed effectively (P＜0.05). Conclusions NF-κB activation correlates with retinal neovascularization closely. PDTC may inhibit the NF-κB activation and prove beneficial in the treatment of ischemic neovascularization. (Chin J Ocul Fundus Dis，2003，19：201-268)
ObjectiveTo investigate the inhibitory effect of lentivirus-mediated polypyrimidine bundle binding protein-associated splicing factor (PSF) on retinal neovascularization (RNV) in mice model of oxygen-induced retinopathy (OIR).MethodsOne hundred and twelve 5-day-old C57BL/6J mice were randomly divided into normal control group, simple OIR model group, OIR model + lentivirus empty vector treatment group (Vec group) and OIR model + PSF lentivirus treatment group (PSF group), with 16, 32, 32 and 32 mice, respectively. When the mice were 7 days old, the mice in the normal control group were fed in a routine environment, and the mice in the OIR model group, Vec group and PSF group were established OIR model. The mice in the Vec group and PSF group were given an intravitreal injection of 1 μl of lentiviral vector and PSF lentivirus (titer 1×1011 TU/ml) at the age of 12 days. No injection was performed in the normal control group and simple OIR group. RNV was evaluated by counting the number of pre-retinal neovascular cells and analysis of non-perfusion area by immunofluorescent staining of the mouse retina. Real-time quantitative PCR was applied to detect the mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). Western blot analysis was applied to detect the protein expression of Nrf2, HO-1 and PSF. Results Of the normal control group, simple OIR model group, Vec group and PSF group, the number of pre-retinal neovascular cell nuclei were 0.00, 14.36±5.50, 15.67±4.96, 8.13±2.09, the non-perfusion area were 0.00%, (35.71±2.81)%, (36.57±4.53)%, (15.33±4.75)%, respectively. The differences of the number of pre-retinal neovascular cell nuclei and non-perfusion area among 4 groups were significant (F=24.87, 165.70; P＜0.05). Compared with the normal control group, there were more pre-retinal neovascular cell nucleis and larger non-perfusion area in the simple OIR model group and Vec group (P＜0.05). Compared with the simple OIR model group and Vec group, there were lower pre-retinal neovascular cell nucleis and smaller non-perfusion area in the PSF group (P＜0.05). Real-time quantitative PCR and Western blot showed that the mRNA expression of Nrf2, HO-1 (F=53.66, 83.54) and protein expression of Nrf2, HO-1 and PSF (F=58.38, 52.69, 24.79) among 4 groups were significant (P＜0.05). The mRNA expression of Nrf2, HO-1 and protein expression of Nrf2, HO-1 and PSF in the simple OIR model group and Vec group decreased significantly than those in the normal control group (P＜0.05). The mRNA expression of Nrf2, HO-1 and protein expression of Nrf2, HO-1 and PSF in the PSF group were increased significantly than those in the simple OIR model group and Vec group (P＜0.05). model group and Vec group (P＜0.05).ConclusionIntravitreal injection of lentivirus-mediated PSF inhibits RNV in mice model of OIR possibly through up-regulating the expression of Nrf2 and HO-1.
Objective The observe the effects of interferon-inducible protein-10 (IP-10) on proliferation, migration and capillary tube formation of human retinal vascular endothelial cells (HREC) and human umbilical vein endothelial cells (HUVEC). Methods The chemokine receptor (CXCR3) mRNA of HREC and HUVEC were quantified by reverse transcriptase polymerase chain reaction (RT-PCR). In the presence of the different concentrations of IP-10, the difference in proliferation capacity of HREC and HUVEC were analyzed by cell counting kit-8 (CCK-8) methods. Wound scratch assay and threedimensional in vitro matrigel assay were used for measuring migration and capillary tube formation of HREC and HUVEC, respectively. Results RT-PCR revealed both HREC and HUVEC expressed CXCR3. The proliferation of HREC in the presence of IP-10 was inhibited in a dosagedependent manner (F=6.202,P＜0.05), while IP-10 showed no effect on the inhibitory rate of proliferation of HUVEC (F=1.183,P＞0.05). Wound scratch assay showed a significant reduction in the migrated distance of HREC and HUVEC under 10 ng/ml or 100 ng/ml IP-10 stimulation (F=25.373, 23.858; P＜0.05). There was no effect on the number of intact tubules formed by HREC in the presence of 10 ng/ml or 100 ng/ml IP-10. The number of intact tubules formed by HREC in the presence of 1000 ng/ml IP-10 was remarkably smaller. The difference of number of intact tubules formed by HREC among 10, 100, 1000 ng/ml IP-10 and nonintervention group was statistically significant (F=5.359,P＜0.05). Conclusion IP-10 can inhibit the proliferation, migration and capillary tube formation ability of HREC and the migration of HUVEC.
Up-regulation of vascular endothelial growth factor (VEGF) is demonstrated to be a key role in formation process of intraocular neovascularization. Anti-VEGF treatment is the breakthrough of intraocular neovascular diseases therapy. Intrav itreal injection of antineovascularization drug looks to be an effective method on ocular neovascular diseases which with the advantages of good biocompatibility, low prices and longer intravitreal half-time etc. However, at present, it lack of multi-center study; the long-term efficacy and the systematic safety needs the further clinical verification. Various types of CNV showed the different therapeutic reactions to either PDT or Anti-VEGF agent, the treatment methods for exudative AMD include laser, PDT, and drug like Triamcinolone Acetonide，several anti-VEGF preparations. Therefore, understanding the pathogenesis of neovascular AMD and choosing a reasonable therapeutic methods are necessary. We should try to explore a safe, effective, economic, new approach. （Chin J Ocul Fundus Dis，2008，24：157-159）