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 observe the inhibitory effect of endostatin (ES) on oxygen-induced retinal neovascularization.MethodsThirtyfour 7-day-old C57BL/6J mice were randomly divided into 3 groups: oxygen-exposed group (12 mice), ES group (12 mice) and the control group (8 mice). The mice in oxygen-exposed and ES group were exposed to (75±5)％ oxygen for 5 days and then back to the normal air. In ES group, 1 μg ES endostatin were injected into vitreous in one eye, while PBS was injected into the other eye as the control 12 and 36 hours after being exposed to oxygen. The mice in the control group were fed in normal circumstance. The changes of retinal neovascularization was examined by fluorescence angiography with fluorescein isothiocyanatedextran. The number of endothelial cells breaking through the internal limiting membrane (ILM) was counted and the inhibitory effects of ES on retinal neovascularization was observed.ResultsCompared with the oxygen-exposed group, the branches of retinal vessels went normal without any un-perfused area in ES group. The number of nuclei of endothelial cells breaking through ILM on each retinal crosssection decreased to (5.39±1.52), which differed much from that in the oxygen-exposed group (22.56±2.13) (plt;0.001).ConclusionES can effectively inhibit the formation of retinal neovascularization in rats and might be a new path of the treatment for proliferative retinopathy.(Chin J Ocul Fundus Dis, 2005,21:314-317)
Objective To investigate auto-cortex of crystalline lens-induced neovascular epiretinal membrane（NVERM）by micro-injuring posterior c apsule of crystalline lens. Methods twenty four C57BL/6 mouse between 4-6 weeks were selected, and divided into two groups randomly: auto-cortex of crystalline group and the control group. The auto-cortex of crystalline group was treated by penetrating the posterior capsule of lens and washing out the lens cortex into the mouse vitreous using PBS (phosphate buffered solution), while the control group were injected PBS into vitreous merely. Clinical change s were followed by slit-lamp examination and photograph. The eye balls were enu cleated at the day of 3, 7, 14 and 28 after operation. Both HE and immunohistoch emistry were used to detect the pathological changes. Results postoperative one to three days, 11 of 12 mouse in autocortex of crystalline g roup, lens appear to alba turbid at different levels one after another, and then develop into highdensity chinaware white. Postoperative (po) three days, HE s taining shows cortex of lens debris transmigrated in vitreous cavity, and some o f which approached to internal limiting membrane and lead it to rough and discon tinue; Po7-14 days, the capillary in retina expanded, migrated and broke though t internal limiting membrane which got to the pro retina and became the new ves sels. And typical NVERM were observed. Po28 days, some vascularslike structure formed in vitreous cavity. None of mouse in control group developed NVERM. Conclusion Auto-cortex of crystalline lens can induced neovascular epiretinal membrane in C57BL/6 mouse. (Chin J Ocul Fundus Dis,2008,24:118-121)
Objective To determine the effect of posterior vitreous detachment on the prognosis of branch retinal vein occlusion (BRVO). Methods One hundred and sixteen patients (116 eyes) with BRVO who underwent vitreous examination were retrospectively studied.The relati onship of vitreous conditions to posterior segment neovascularization and macular edema was statistically investigated. Results In 40 ischemic cases,12 of 25 eyes (48.0%) with no posterior vitreous detachme nt (PVD) or partial PVD developed retinal or optic disc neovascularization ,or both,but only one of the 15 eyes (6.7%) with complete PVD developed neovasculariz ation during a mean follow-up period of 10.7plusmn;2.2 months (Plt;0.05) . Diffuse macular edema was found in 45 eyes (38.8%).The incidence o f macular edema was significantly higher in eyes with vitreomacular attachment (51.5%) than in those with vitreomacular separation (22.0%) (Plt;0.01). Conclusion It was suggest ed that compl ete PVD may play a role in protecting eyes with BRVO from posterior segment neov ascularization and macular edema. (Chin J Ocul Fundus Dis, 2001,17:2-4)
Objective To observe the inhibitory effect of Bevacizumab on retinal neovascularization in oxygen-induced retinopathy in the mouse. Methods 90 one-week-old C57B L/6J mice were divided into four groups at random. 15 mice in the 1st group as normal control group, 15 mice in the 2nd group as oxygen control group, 30 mice in the 3rd group as high-dose Bevacizumab treatment group, 30 mice in the 4th group as low-dose Bevacizumab treatment group. The 2nd, 3rd and 4th groups were exposed to 75% oxygen for 5 days and then to room air. At the 12th day, One eye of each mouse of two control groups were received an intravitreal injection with Be vacizumab at 2 mu;l、1 mu;l respectively, and the same volume of BSS was injected into the other eye of the mice. The adenosine diphosphatase (ADPase) histochemical technique was used for retinal flat mount to assess the oxygen-induced change s of retinal vessels. The number of the endothelium cell nuclei of proliferative neovascularization was quantified by retinal microtome chromoscopy. Real-time PCR analysis was performed to examine the expression of VEGF mRNA. Results Comparing with oxygen control group, regular distributions, reduced density of retina l vascular and reduced endothelium cell nuclei which extending retinal membrane were observed in the treatment groups(P＜0.001). But the differences between two treatment groups are not statistically significant (P＞0.05). The expression of VEGF mRNA was not significantly different in oxygen control group whatever it whether accepted Bevacizumab treatment or high or low dose (P＞0.05). Conclusion Intravitreal injection with Bevacizumab can effectively inhibits the retinal neova scularization in oxygen-induced retinopathy in the mouse. Intravitreal injection with Bevacizumab might become to the new method to treat retinopathy of premature. （Chin J Ocul Fundus Dis，2008，24：184-188）
ObjectiveTo investigate the inhibitory effects of 5-lipoxygenase (5-LOX) on oxygen-induced retinal neovascularization in mice and to explore its possible mechanisms. Methods7-day-old C57BL/6J mice were randomly divided into normal group, oxygen induced retinopathy (OIR) model group, large-dose group, small-dose group and control group with 12 mice in each group. The mice with their mothers were kept in (75±2)% of oxygen environment for 5 days and then returned to normoxia for 5 days to establish the OIR model except for normal group. From postnatal day 12 to 17, the large-dose group and small-dose group received intravitreous injection of 5-LOX at dose of 100 mg/kg and 50 mg/kg respectively, while the control group received the same volume of 1% dimethyl sulfoxide. The mice in the OIR group received no treatment. The number of endothelium cell nuclei breaking through the inner limiting membrane (ILM) was counted on hematoxylin and eosin-stained retinal section. The mRNA expression of 5-LOX, vascular endothelial growth factor (VEGF)-a, VEGF receptor 2 (VEGFR-2) on retinal tissue were detected by reverse transcription polymerase chain reaction (RT-PCR). The protein expression of 5-LOX, VEGF-a, VEGFR-2 and phosphorylation extracellular signal-regulated kinase (P-ERK) 1/2 on retinal tissue were detected by Western blot. ResultsThe number of vascular cell nuclei breaking through the ILM in the large-dose group and small-dose group decreased significantly compared with the OIR group and control group (F=73.390, P < 0.05). The mRNA expression and protein expression of 5-LOX, VEGFa, VEGFR-2 on retinal tissue were decreased significantly in the large-dose group and small-dose group as compared with the OIR group and control group (F=92.668, P < 0.05). The difference of VEGFR-2 protein expression between large-dose group and small-dose group was not significant (F=2.118, P > 0.05). The differences of 5-LOX, VEGF-a, P-ERK 1/2 protein expression between large-dose group and small-dose group were significant (F=86.490, 165.128, 139.424; P < 0.05). ConclusionHypoxia may induce 5-LOX expression in the retina. Retinal neovascularization was significantly inhibited by selective inhibition of 5-LOX.
ObjectiveTo analyze the expression of miRNA involved in regulating retinal neovascularizationin in retinal tissue of oxygen-induced retinopathy (OIR) mice.MethodsEighty healthy C57BL/6J mice were randomly divided into control group and OIR group at postnatal day 7(P7). Control group were not received any treatment and then exposed to room air. The OIR group was exposed to (75±2)% oxygen and then under room air at P12. Mice of all groups were euthanized at P17. Retinal neovasculation (RNV) was evaluated by counting the number of pre-retinal neovascular cells and analysing no perfusion area by immunofluorescent staining of the mouse retina.Total RNA was extracted from retinal tissue,and miRNA microarrays was performed to identify differentially expressed miRNA in the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed differential microRNA.ResultsCompared with the control group,the retinal neovascular tufts and the no perfusion area were both significantly smaller than those in OIR group. The number of pre-retinal neovascular cell nuclei in retinas from control group were obviously lower than those in the retinas from OIR group (t=9.025, P＜0.05). MiRNA microarray analysis showed that 54 miRNA in OIR group showed statistically different expression in control group, 47 miRNA were up-regulated and 7 miRNA were down-regulated. The results of PCR were consistent with the trend of microarray. In GO analysis, 1112 items were significantly different (P＜0.05), and 65 items were significantly different in KEGG analysis of expression profile (P＜0.05).ConclusionsThe miRNA expression in retinal tissue of OIR mice is different from that of normal mice, and these miRNA may be involved in the development of RNV. There are 54 miRNA expression differences in retinal tissue of OIR compared with normal mouse retinal tissue.
Objective To evaluate the possible role of vascular endothelial growth factor (VEGF) in the pathogenesis of retinal neovascularization resulting from retinal ischemia． Methods Retinal vein occlusion of rabbits model was established with argon laser photo coagulation to retinal vein．The VEGF mRNA expression was observed in ischemic retina and retinal neovascular tissue with in situ hybridization technique． Results VEGF mRNA expression was detected in inner ischemic retina and retinal neovascular tissue that were corespondent to the distribution of retinal ischemia．The best VEGF mRNA expression was detected in retinal neovascular tissue． Conclusion VEGF might play an important role in the pathogenesis of vascular proliferative retinopathy． (Chin J Ocul Fundus Dis, 2001,17:5-7)
Retinal neovascularization is a complicated pathophysiological process as a result of imbalance between angiogenic and antiangiogenic factors. Correct understanding of the signaling pathways, exploring the critical factors involved in retinal angiogenesis, looking for new strategies by reconstructing the new vessels are helpful for knowing the mechanism of the occurrence and development of reitnal neovascularization, which would be good for preventing and treating retinal neovascularization diseases.
PURPOSE:To observe the clinical features of the macular hemorrhage in myopes. METHOD:Twenty-four patients(30 eyes)with myopic macular hemorrhage were examined with slitlamp biomicroscopy,funduscope,A/B ultrasonography,and fundus fluorecein angiography(FFA). The patients were followed up for 3~18 months(average 12 months). RESULTS: Four of 26 eyes with macular hemorrhage examined with FFA were found to be due to choroidal neovaseulature,and they were associated with posterior staphyloma. The other 22 eyes without neovascular change were thought to be simple type,and 19 of them were associated with lacquer cracks. The hemorrhage in simple type cases deminished usually within 1~3 months. CONCLUSION:Myopic macular hemorrhagic eyes of neovascular type resulted usually in recurrent hemorrhage and worse prognosis in visual acuity than those of simple type. （Chin J Ocul Fundus Dis,1996,12: 220-222）