ObjectiveTo evaluate the inhibitory effect of small interfering RNA (siRNA) targeting peroxisome-proliferator-activated receptor-γcoactivator-1α(PGC-1α) on retinal neovascularization in the mouse. MethodsEighty seven-day-old C57BL/6J mice were divided into normal group, model blank group, model control group and PGC-1αsiRNA group, twenty mice in each group. Mice in the normal group were kept in normal room air. Mice in the model blank group, model control group and PGC-1αsiRNA group were induced for retinal neovascularization by hypoxia. Liposome with PGC-1αsiRNA (1 μl) and liposome with negative control siRNA (1 μl) were injected into the vitreous in the PGC-1αsiRNA group and model control group respectively when mice were moved out to room air from the cabin (Postnatal 12). No injection were performed in the model blank group. At postnatal 17, fluorescein angiography was used to assess the vascular pattern.The proliferative neovascular response was quantified by counting the nuclei of new vessels extending from the retina into the vitreous in cross-sections. PGC-1αand vascular endothelial growth factor (VEGF) level in retina were measured by real-time polymerase chain reaction (real-time PCR) and Western blot. Inhibition efficiency of PGC-1αsiRNA on PGC-1αand VEGF was calculated. ResultsMice in the normal group showed reticular distribution of retinal blood vessels. Central nonperfused retina, neovascular tufts and fluorescein leakage were seen in the model blank group and model control group. Neovascular tuft and fluorescein leakage were decreased in the PGC-1αsiRNA group compared to the model blank group and model control group. The neovascular nuclei were increased in the model blank group and model control group compared to the normal group (P < 0.05). The neovascular nuclei were decreased in the PGC-1αsiRNA group compared to the model blank group and model control group (P < 0.05). The expression of PGC-1αmRNA and protein in retina was increased significantly in the model blank group and model control group as compared with normal group, while decreased 54% and 53% respectively in the PGC-1αsiRNA group as compared with model blank group and model control group (P < 0.05). The expression of VEGF mRNA and protein in retina was increased significantly in the model blank group and model control group as compared with normal group, while decreased significantly in the PGC-1αsiRNA group (decreased 48% and 40% respectively) as compared with model blank group and model control group (P < 0.05). ConclusionsIntravitreal injection of PGC-1αsiRNA mediated by liposome can inhibit retinal neovascularization in the mouse effectively.
Objective To investigate the effect of suppression of ischemia-induced retinal neovascularization by VEGF antisense oligodeoxyribonucleotides. Methods Mouse models of hyperoxia-induced ischemic retinopathy were established. Retrobulbar injections were performed with VEGF antisense oligodeoxyribonucleotides or NS in 4 groups:normal control and various doses respectively. The nuclei of new vessel buds extending from the retina into the vitreous in differ ent groups were counted and compared under the light microscope. Results There were plenty of new vessel buds in the eyes of mice in hyperoxic condition., while the number of the nuclei of new vessel buds is less in the murine eyes with retrobulbar injection of VEGF antisense oligodeoxyribonucleotides,especially the nuclei were redused with 59.3% in eyes with large dose. Conclusion The proliferation of retinal new vessel may be suppressed by using the retrobulbar injection of VEGF antisense oligodeoxyribonucleotides. (Chin J Ocul Fundus Dis, 2001,17:141-143)
Objective To compare the characteristics of the results of fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) in patients with classic choroidal neovasculazation (CNV). Methods The data of FFA and ICGA of 34 patients (36 eyes) with classic CNV were analyzed retrospectively and the results of the two examinations were analyzed contrastively. Results The results of FFA revealed the clew or cartheel-tike configuration of classic CNV at the early phase in 3 out of 15 eyes (20%) with age-related macular degeneration (AMD); in 5 out of 7 eyes with pathological myopia(71.4%); and in 9 out of 14 eyes with central exudative chorioretinopathy (CEC),(64.3%),In 36 eyes with classic CNV, the images of ICGA indicated CNV distinctly in 20 (55.6%) and indistinctly in 15 (41.6%); CNV was not detected by ICGA in 1 eye (2.8%); feeding blood vessels in 6 eyes (16.7%) were detected by ICGA but none by FFA. Conclusions At the early phase of FFA, the configuration of classic CNV is clew-like in eyes with pathological myopia and CEC, and erose in eyes with AMD. The image of ICGA which indicated the outline of classic CNV is not as clear as the one of FFA, but it can reveal the feeding vessels which FFA can not. (Chin J Ocul Fundus Dis, 2006, 22: 217-209)
Objective To investigate the role of bone marrow-derived cells (BMC) plays in choroidal neovascularization (CNV).Methods Green fluorescent protein (GFP) chimeric mice were built by transplanting BMC from GFP transgenic mice to adult wild type C57BL/6J mice. Retinal laser photocoagulation was used to induce CNV in the chimeric mice (treated group) and adult wild type mice (control group). Four weeks later, choroidal flatmount was prepared to detect GFP positive BMC expression in the CNV lesions, and immunofluorescence stain was used to determine the expression of vascular endothelia growth factor (VEGF) and basic fibroblast cell growth factor (bFGF).Results Twenty-nine days after photocoagulation lots of GFPpositive BMC presented in the CNV area, which accounted approximate 16.22% of the total CNV area. Some BMC in the CNV area expressed VEGF and bFGF. Conclusions BMC may play an important role in CNV by forming new vessles and secreting angiogenic factors.
ObjectiveTo observe the clinical efficiency of intravitreal Conbercept on exudative age-related macular degeneration (eAMD). MethodsThis is an open and prospective study without control trial. Twenty eyes from 20 patients (19 males and 1 female) with eAMD diagnosed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were enrolled in this study. Before the injection, best-corrected visual acuity (BCVA) of early treatment of diabetic retinopathy study (ETDRS), non-contact tonometer, ophthalmoscope, fundus photography, fundus fluorescein angiograph (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) were examined. The initial average letters of ETDRS acuity were 41.20±22.61, range from 8 to 80. The initial average central retina thickness (CRT) was (345.25±131.96) μm, range from 152 to 770 μm.All affected eyes were treated with intravitreal conbercept 0.05 ml (10 mg/ml). The patients were followed up for 6 to 9 months, with the mean time of (7.35±0.99) months.The BCVA, CRT after treatment were compared with baseline using paired t-test. ResultsDuring the 1, 3, 6, 12 months after treatment and the latest follow up, the mean BCVA were all improved with statistically significant difference (t=5.85, 7.09, 7.44, 7.25; P < 0.05). At 1 month ater treatment, the mean BCVA was obviously improved in 6 eyes (30%), improved in 8 eyes (40%), stable in 6 eyes (30%). At latest follow up, the mean BCVA was obviously improved in 6 eyes (30%), improved in 9 eyes (45%), stable in 5 eyes (25%). During the 1, 3, 6, 12 months after treatment and the latest follow up, the mean CRT were all decreased with statistically significant difference (t=3.34, 3.78, 3.47, 3.44; P < 0.05). At latest follow up, the leakage in macula lutea disappeared in 6 eyes (30%), decreased in 11 eyes (55%) and increased in 3 eyes (15%). No adverse events such as secondary retinal detachment or endoophthalmitis were found during the follow-up duration. ConclusionIntravitreal conbercept is a safe and effective approach for eAMD, may improve visual acuity, exudation and macular edema.
The diagnosis and treatment of age-related macular degeneration (AMD) is an international hotspot of eye research. Successful clinical applications of antiVEGF drugs promoted both basic research and clinical practice of AMD. A number of countries and professional societies have established clinical guidelines for AMD management, including the epidemiology, risk factors, diagnosis, classification, and treatment process. These AMD guidelines are mostly based on recently published results of clinical trials, provided good model of evidence based medicine. It is urgent and necessary to have our own guideline which is suitable for Chinese patients. Reviewing and learning existed guidelines will help us to improve the clinical practice of AMD in China.