PURPOSE:To investigate the spatial and temporal relation of fibronectin(Fn),basic fibroblast growth factor(b-FGF)and astrocytes with the retinal vascular developmemt of human fatuses.
METHODS:The retinas of 86 human fetuses from 13th week to 40th week were studied by immunohistochemical methods and light microscopy.
RESULTS:Fn immunoreativity was localized in spindle cells ,vascular endothelial cells and extracellular matrix ahead of the spindle cells,vascular endothelial cells,ganglion cells and cone cells were b-FGF immunopositive. The b-FGF immunoreactivity in ganglion cells and cone cells appeared earlier than the vascularization nearby.Astrocytes migrated to ora serrata in close association with the spindle cells.and sent numerous processes to ensheath the blood vessels formed in two processes of retinal vascuiarlzation.
CONCLUSION:These results suggest that Fn ,b-FGF and astrocytes were involved in modulating both of two processes of retinal vascularizalion.
（Chin J Ocul Fundus Dis,1996,12:180-182）
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）
Two-hundred and forty-five eyes of 240 cases of branch retinal vein occlusion (BRVO) were analysed to determine the risk factors influencing the development of retinal neovascularization (NV).There were 208 eyes with major BRVO, 37 eyes with macular BRVO, 79 eyes with major BRVO developed NV, and the incidence of NV in this series was 37.9%.The incidence of vitreous hemorrhage in these eyes was 15.9%(39 eyes). The risk factors influencing the development of retinal NV in BRVO seem as follows: (]) the extent of retinal capillary nonperfusion area, (2)inefficiency of arterial infusion, (3) the extent of venous block at the arteriovenous crossing, (4) the duration of follow-up since onset of BRVO, and (5) the lack of collateral formation, Because BRVO has a long natural history, it is recommended that the patients should be followed-up for a long time If the vessels at peripheral retina closed, fluorescein angiography should be performed without hesitation and if the nonperfusion area is greater than 20-30 disc area, one should follow the patient carefully.As soon as the new vessels appear, laser photocoagulation should be applied without delay.
（Chin J Ocul Fundus Dis,1994,10:67-70）
Objective
To assess the effectiveness of transpupillary thermotherapy (TTT) for the treatment of central exudative chorioretinopathy.
Methods
Tweenty-nine eyes with central exudative chorioretinopathy were treated with Iris 810 nm diode laser TTT. The laser beam size was 1.0, 2.0 or 3.0 mm with power settings between 80-300 mW and treatment time 60 sec. The follow up periods were wihzin 4-40 weeks. The therapeutic effect was accessed by visual acuity examination,dinect ophthalmoscopy and fluorescein or indocyanine green angiography.
Results
The visual acuity improved in 8 eyes (28%), remained no change in 19 eyes (65%) and decreased in 2 eyes (7%). Choroidal neovascularization were closed in 12 eyes in fundus angiography. The symptoms alleviated in 10 patients.
Conclusion
Transpupillary thermotherapy is a potential treatment for the central exudative chorioretinopathy.
(Chin J Ocul Fundus Dis, 2002, 18: 184-186)
ObjectiveTo observe the expression of Rap1, guanosine triphosphate-Rap1 (GTP-Rap1), vascular endothelial growth factor (VEGF) and β-catenin in experimental choroidal neovascularization (CNV).MethodsForty-two brown Norwegian rats were randomly divided into a blank control group (7 rats) and a model group (35 rats). Both eyes were enrolled. The CNV model was established by holmium ion laser photocoagulation in the model group. At 3, 7, 14, 21, and 28 days after photocoagulation, fluorescein fundus angiography (FFA) and choroidal vascular smear were performed to observe the degree of fluorescein leakage and CNV area in rats; Western blot and real-time quantitative polymerase chain reaction (RT-PCR) were used to detect the expression of Rap1, GTP-Rap1, VEGF, β-catenin and mRNA in CNV.ResultsThe results of FFA examination showed that a large disc-shaped fluorescein leaked in the photo-condensation spot 14 days after photocoagulation. Laser confocal microscopy showed that compared with 7 days after photocoagulation, CNV area increased at 14, 21, 28 days after photocoagulation, and the difference were statistically significant (t=3.725, 5.532, 3.605;P＜0.05). Western blot showed that there was no significant difference in the relative expression of Rap1 protein in CNV at different time points after photocoagulation between the two groups (P=0.156). Compared with the blank control group, the relative expression of GTP-Rap1 protein was significantly decreased, the relative expression of VEGF and β-catenin protein were significantly increased in the model group (P=0.000). The results of RT-PCR showed that there was no significant difference in the relative expression of Rap1 mRNA at different time points after photocoagulation between the two groups (P=0.645), but there were significant difference in the relative expression of β-catenin mRNA (P=0.000). At 7, 14, 21 and 28 days after photocoagulation, there were significant difference in the relative expression of GTP-Rap1 and VEGF mRNA between the two groups (P=0.000).ConclusionsThe expression of GTP-Rap1 in experimental CNV is significantly lower than that in normal rats.
