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.
Objective To observe the inhibitory effects of construction of complement factor (CFB)small interference RNA (siRNA) on choroidal neovascularization（CNV）induced by photocoagulation in rats.Methods We constructed an expression vector of CFBsiRNA by cutting CFBsiRNA and plasmid pRNATU61/Neo. Experimental CNV was induced by photocoagulation in 42 Brown Norway rats. After the model was set up, the rats were randomly divided into tail intravenous injection, vitreous injection, subretinal injection, and control group; each group except the control one had a corresponding blank plasmid control group. CFBsiRNA was injected 1, 3, and 5 days respectively after photocoagulation in the injection groups; the dosage was 50, 20, and 10 mu;g in tail intravenous injection, vitreous injection, and subretinal injection group respectively, while no injection was give to the control group after photocoagulation. Before and 14 days after photocoagulation, fundus fluorescein angiograoph (FFA) was performed and CNV development was judged by the leakage; the expression of vascular endothelial growth factor (VEGF) and factor Ⅷ were detected by immunohistochemistry. Results The leakage of fluorescein was obvious lower in tail intravenous injection group than that in the control group (chi;2=15.1620,Plt;0.05). The expression of VEGF and factor VIII in tail intravenous injection group at different time points after photocoagulation didnprime;tdiffer much (F=20.35,18.33; Pgt;0.05); while was apparently lower than that in the other groups at different time points (F=77.96,55.68; Plt;0.05).All of the groups, except tail intravenous injection group, had higher expression of VEGF and factor VIII 14 days after photocoagulation compared with that 7 days after photocoagulation (F=60.89, 61.12; Plt;0.05).Conclusions Constructed CFBsiRNA can inhibite CNV by downregulating the expression of VEGF and factor Ⅷ.
Objective To summarize the therapeutic effect and clinical characteristics of repetitive photodynamic therapy (PDT) for patients with exudative age-related macular degeneration (AMD). Methods The clinical data from 78 patients (94 eyes) with exudative AMD who had undergone PDT from July, 2002 to March, 2005 were retrospectively analyzed. The average age of the patients was 68.4, and the treated times was 132 (mean 1.4). Thirty eyes underwent PDT 68 times, including twice in 22 eyes (73.3%), 3 times in 7 eyes (23.3%), and 6 times in 1 eye (3.3%). The follow-up period lasted 3-32 months with the average of 16.7 months. Results In the final follow-up examination, the results of fundus fluorescein angiography or combined with indocyanine green angiography showed that the leakage of choroidal neovascularization (CNV) stopped in 14 eyes (46.7%), reduced in 12 (40%), and remained in 4 (13.3%). Compared with the condition before first PDT, the correct visual acuity increased ge;2 lines in 7 eyes (23.3%), changed plusmn;1 line in 14 eyes (43.3%), and decreased ge;2 lines in 9 eyes (30%) in the final examination. After first PDT, the best corrected visual acuity increased ge;2 lines in 13 eyes (43.3%), changed plusmn;1 line in 12 eyes (40%), and decreased ge;2 lines in 5 eyes (16.7%). During the follow-up period, the best corrected visual acuity occurred after first PDT in 24 eyes (80%), after second PDT in 5 eyes (16.7%), and after third PDT in 1 eye (3.3%). Conclusions In patients undergone repetitive PDT, CNV in most of the affected eyes completely or partly closed and the visual acuity improved or remained still in 67.8% of the patients in the final follow-up examination. The best correct visual acuity mainly happened after the first PDT, and as the times of PDT increased, the probability of the best correct visual acuity decreased. (Chin J Ocul Fundus Dis, 2006, 22: 220-223)
Objective To investigate the therapeutic efficacy of transpupillary thermal therapy (TTT) for age-related macular degeneration (AMD) accompanied with subfoveal choroidal neovascularization (CNV). Methods Fifty-one eyes of 47 patients whose illness had been diagnosed as AMD by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were treated with diode 810 laser. There are 42 eyes of 39 patients had occult CNV and 9 eyes of 8 patients had classic CNV, and the average visual acuity in their fist diagnosis was 0.12. According to the focus size, the diameters of beam spot varied from 0.8, 1.2, 2.0, and 3.0 mm; and the power was 120, 160, 260 and 360mW correspondingly, with the duration of 60 seconds. The follow-up examination was performed once a month after the treatment, and repetitious treatment would be taken once to thrice if necessary. The follow-up period was 3~33 months with the mean of 10 months. Visual acuity, haemorrhage in ocular fundus, absorption of exudation, and the closure of CNV were examined in the follow-up examination. Results No immediate decrement of visual acuity or any other discomforts were found in all of the treated eyes soon after the treatment. The average visual acuity of 51 eyes was 0.16 in the last diagnosis, which remained no change in 68.62%; increased in 23.53% and decreased in 7.84% compared with that in the first diagnosis. The results of FFA and ICCG demonstrated that at the 3rd months after the treatment, the closure rate was 42.86% in occult CNV and 22.22% in classic CNV; and at the 6th month, the closure rate was 73.81% in occult CNV and 66.67% in classic CNV. The results of ophthalmoscopy showed that at the 3rd month after the treatment, partial or complete absorption of hemorrhage and/or exudates with various thickness of organized scarring tissue was found in 42 eyes with occult CNV; decrement of hemorrhage and exudates was observed in 7 out of 9 eyes with classic CNV; and new hemorrhage occurred in 1 eye. At the 6th month, in 27 eyes with occult CNV, new hemorrhage occurred in 3 including 2 eyes with occult CNV, new hemorrhage occurred in 3 including 2 eyes with faster absorption and remaining unchanged for 12 months; in 5 eyes with classic C NV, new hemorrhage occurred in 2, which was absorbed after treated again and remained stable in the 16-month followed-up. In 19 eyes with occult CNV which had been followed up for more than 6 months, hemorrhage disappeared in 5 and new hemorrhage occurred in 5. In the followed-up over 6 months, new hemorrhage occurred in 8 eyes with the recurrent rate of 15.6%. Conclusion TTT is effective for AMD with either classic or occult CNV. In the long-term followed-up, CNV recurs in 15.6% of the treated eyes which may be improved after the further treatment. (Chin J Ocul Fundus Dis，2004，20：280-284)
Interleukin-18 is an inactive precursor which lacks a signal peptide, it has a role in regulating retinal pathological angiogenesis. It also inhibits experimental choroidal neovascularization (CNV) via interferon-γand thrombospondin-1. Currently little is known about its mechanisms of inhibition for CNV, may be speculated to be due to effects of anti-angiogenesis, down-regulates vascular permeability and lower vascular endothelial growth factor (VEGF) levels via directly acting on the vascular endothelial cell and epithelial cells. Exogenous administration of mature recombinant interleukin-18 has no adverse effect on retinal pigment epithelial cell viability. In addition, the anti-VEGF role of interleukin-18 is tested to be safe and effective for humans. Interleukin-18 alone or in combination with anti-VEGF shows to be a good prospect for improving the prognosis of experimental CNV. However, more large clinical studies are required to confirm the exact efficacy of interleukin-18 for CNV.
ObjectiveTo summarize the clinical results and safety of photodynamic therapy (PDT) through 4 years after single and multi-treatments of patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration(AMD). MethodsClinical data of 73 AMD cases (95 eyes) diagnosed through fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optic coherence tomography (OCT), treated with PDT were reviewed and analyzed in this hospital from June 2000 to June 2004. The changes of best corrected visual acuity (BCVA), fundus pictures, FFA, ICGA and OCT were compared before and after PDT. Follow-up time varied from 3 months to 4 years (mean, 2 years). ResultsThe mean age of 73 patients was 67.8 years old. The BCVA was from CF/10 cm to 1.0. At the final follow up, the BCVA was improved (increase≥2 lines) in 39 eyes (41.1%), stabilized (±1 line) in 51 eyes (53.7 %) and decreased 2 lines in 5 eyes (5.3%). Fundus hemorrhage and exudation reduced after PDT. FFA and ICGA showed CNV complete closure in 58 eyes (61.05%), partial closure in 6 eyes (6.32%), CNV incomplete closure in 22 eyes (23.16% ) and recurrence in 9 eyes (9.47%). After once PDT of 12 eyes with early-stage AMD, the BCVA improved (from 0.6 to 1.5), CNV completely closed, and the OCT showed disappearance of macular edema and neursensory retinal deta chment. No CN V recurred in our four years follow-up observation and the BCVA of the patients remained stable. The mean number of PDT treatment was 1.8 per eye in 95 cases. No serious local or systemic complications were encountered. ConclusionsSingle or multiple sessions of PDT can acheive long-term safety and efficacy. For early-stage AMD patients with minimally classic CNV, PDT can completely make CNV closed and reduce the risk of visual loss.(Chin J Ocul Fundus Dis，2004，20：275-279)
Pathological myopia can induce choroidal neovascularization (PM-CNV). The potential risk factors include ageing, long axial length of the eyeball, thinning of subfoveal choroidal thickness, fundus atrophy spot and lacquer crack. These factors may induce atrophy of retinal pigment epithelial cells (RPE) and hypoxia, resulting in vascular endothelial growth factors (VEGF) secretion by outer retina. The lesion type, location and activity of PM-CNV can be determined by fundus fluorescein angiography. The features of PM-CNV on optical coherence tomography include strong reflective area close to RPE with very small amount of subretinal fluid (active stage), surface strong reflection with signal attenuation area (scar stage) and flat lesion and chorioretinal atrophy (atrophy stage). Photodynamic therapy and intravitreal injection of anti-VEGF drugs are major treatments for PM-CNV, the latter is more commonly used now. However, more large randomized controlled studies are required to explore the treatment regimen (such as frequency, indications for repeated or termination of treatment) and the efficacy factors further.