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)
Axon guidance molecules, slit glycoprotein (Slit) and Roundabout receptors (Robo) were firstly identified in the central neural system of Drosophila melanogaster. The Slit-Robo signal plays a crucial role in axon guidance, inflammation, tumor metastasis and angiogenesis, of which the role of Slit2-Robo pathway in angiogenesis has drawn a greater attention and still remains conflicting. Herein, we provide a review on the role of Slit2-Robo pathway in ocular angiogenesis and vascularization of other organs and systems. We hope this review will be the basis of further study on the mechanism of Slit2-Robo signaling on angiogenesis and provide new target for the therapy on ocular vascular disease
Objective To observe the baseline characteristics and visual outcomes after two years follow-up of exudative age-related macular degeneration (AMD) patients treated with ranibizumb. Methods Forty-four eyes of 44 patients with exudative AMD were enrolled into this retrospective study, 19 were men and 25 were women. The mean age was 78 years (range 64 – 92 years). All patients were underwent best corrected visual acuity (BCVA, Early Treatment of Diabetic Retinopathy Study), fundus color photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT). The mean BCVA was (50.36±14.43) letters, the mean central foveal thickness (CFT) was (291.95±82.19) μm, and the fluorescence leakage area of choroidal neovascularization (CNV) was (7.61±5.84) mm2. All patients received three initial intravitreous injection of ranibizumb (IVR) and were retreated with monthly IVR when needed. The mean follow up time was 25.6 months (range 24 – 29 months). On 1, 2, 3, 6, 12, 18 and 24 months after treatment, BCVA and OCT were repeated. On 3, 6, 12, 18 and 24 months after treatment, FFA and ICGA were repeated. The change of BCVA, CFT and fluorescence leakage area of CNV were observed. The association of baseline characteristics and two year visual outcomes were analyzed. Results On 1, 2, 3, 6, 12, 18 and 24 months after treatment, the BCVA were improved significantly (t= −1.89, −3.51, −4.61, −4.04, −5.77, −4.69;P＜0.05), the CFT were decreased significantly (t=1.51, 2.30, 3.40, 3.28, 3.54, 3.88, 3.73;P＜0.05). On 3, 6, 12, 18 and 24 months after treatment, the fluorescence leakage area of CNV were reduced significantly (t=2.12, 2.90, 3.51, 4.12, 4.06;P＜0.05). The lower baseline BCVA, the more improved after treatment. The BCVA improvement degree has a negative relationship with baseline BCVA and fluorescence leakage area of CNV (r=0.505, −0.550;P＜0.05), but no correlation with baseline CFT (r=0.210,P＞0.05). Conclusion Two year visual outcomes of exudative AMD patients treated with ranibizumb is negative correlated with baseline BCVA and fluorescence leakage area of CNV, but not correlated with baseline CFT.
ObjectiveTo explore the antitumor effect of tumor vaccine fused from dendritic cells (DC) and Walker-256 cancer cells on implanted liver cancer in rats and the related mechanism of inhibition for tumor angiogenesis. MethodsWalker-256 cancer cells and mature DC were fused by 50% polyethylene glycol method for preparation of DC-Walker-256 fusion vaccines. Implanted liver cancer models were established through operations on healthy male SD rats at the age of 6－8 weeks. All the rats were divided into four groups, and rats in each group were injected subcutanely with fusion vaccine (group), mixed cultured cells (group), simple DC (group), and PBS (blank control group), respectively. On 28 d after making model, the rats were put to death, the tumor was observed and pathological essays were prepared. All rats’ spleens were collected and prepared into lymphocyte to detect antigenic specificity cytotoxic T lymphocyte (CTL) by enzymelinked immunosorbent spot (ELISPOT) method. The expressions of VEGF, ANG-1, ANG-2, and MVD were detected by immunohistochemistry. ResultsThe numbers of rats survived in the fusion vaccine group, mixed culture cells group, simple DC group, and blank control group was 8, 5, 6, and 3, respectively. The rats in the other three groups except for fusion vaccine group were manifested as inaction, anorexia, and gloomy fur in some degree as well as ascites. The tumorigenesis was found in all survival rats except for two in the fusion vaccine group. The weight of liver tumors of rats in the fusion vaccine group 〔(32.4±9.2) g〕 was significantly lighter than that in the mixed culture cells group 〔(67.3±5.1) g, P=0.031〕, simple DC group 〔(75.0±8.3) g, P=0.019〕, and blank control group 〔(86.6±10.5) g, P=0.008〕, respectively. The number of tumorspecific CTL of rats in the fusion vaccine group was also significantly higher than that in the other three groups (P=0.019, P=0.025, and P=0.001, respectively). The MVD of tumor tissue in the fusion vaccine group was (24.12±2.32) vessels/HP, which was significantly lower than that in the mixed culture cells group 〔(40.34±1.29) vessels/HP, P=0.025〕, simple DC group 〔(42.36±3.16) vessels/HP, P=0.035〕, and blank control group 〔(56.48±5.16) vessels/HP, P=0.006〕, respectively. The MVD of tumor tissue in the mixed cultured cells group and simple DC group was similar (P=0.165), however, which was significantly lower than that in the blank control group (P=0.040 and P=0.043). The positive rate of VEGFA protein expression was 23.2% in the fusion vaccine group, which was significantly lower than that in the mixed culture cells group (42.5%, P=0.031), simple DC group (61.3%, P=0.019), and blank control group (89.6%, P=0.003), respectively. The positive rate of VEGF-A protein expression in the mixed cultured cells and simple DC groups was similar (P=0.089), however, which was significantly lower than that in the blank control group (P=0.027 and P=0.038). The positive rate of ANG-1 protein expression in the fusion vaccine group (43.2%) was not different from that in the mixed culture cells group (46.3%, P=0.292), simple DC group (51.3%, P=0.183), or blank control group (49.6%, P=0.179), respectively, and the difference of pairwise comparison in latter three groups was not significant (P=0.242, P=0.347, and P=0.182). The positive rate of ANG2 protein expression was 19.2% in the fusion vaccine group, which was significantly lower than that in the mixed culture cells group (62.3%, P=0.007), simple DC group (67.3%, P=0.005), and blank control group (71.6%, P=0.004), respectively, however, the difference of pairwise comparison in latter three groups was not significant (P=0.634, P=0.483, and P=0.379). ConclusionFused vaccine can induce CD8+ CTL aiming at tumor cells and establish the effective antitumor immunity in vivo and also downregulate the level of VEGF and ANG-2 to suppress tumor angiogenesis and thereby achieve the purpose of curing tumor.
ObjectiveTo study the inhibitory effects of pigment epithelium derived factor (PEDF) on oxygen-induced retinal neovascularization in mice, and to investigate the possible involvement of interleukin-1β (IL-1β) in the neovascular-inhibitory function of PEDF. Methods A total of 140 postnatal day (P)7 C57BL/6 mice were randomly divided into normal control group, oxygen-induced retinopathy (OIR) model group, PEDF treatment group and PBS treatment control group. All mice except normal control group with their mothers were exposed to (75±2)% oxygen environment for 5 days and then kept in room air for another 5 days to establish the OIR model. Mice in normal control group were kept in room air only. At P12 and P14, respectively, mice in PEDF treatment group received intravitreous injections of 1 μl PEDF (2 μg/μl), while PBS treatment control group received the same volume of PBS (10 mmol/L, pH7.4).All mice were euthanized at P17 and eyes were isolated. The changes of retinal vessels were observed on retinal flat mounts and cryosections by fluorescence microscopy. Retinal specimens were prepared for IL-1β protein and mRNA analysis by Western blot and real time fluorescence quantitative reverse transcription-polymerase chain reaction (Real-time RT-PCR). ResultsChanges of retinal vessels had been viewed by fluorescence microscopy on flat-mounted retina, the relative retinal neovascularization areas were significantly increased in OIR model group compared with normal control group (t=15.02, P < 0.01), and the relative retinal neovascularization areas were obviously smaller in PEDF treatment group than those in PBS treatment control group (t=5.96, P < 0.01). Fluorescence staining revealed that retinal vascular tufts were extending from outer plexiform layer (OPL) to ganglion cell layer (GCL) of the retina along with multiple interconnections; Neovascular tufts in OIR model group and PBS treatment control group were presenting distinctly more than those of normal control group and PEDF treatment group. The specific expression levels of IL-1β protein in retinas of OIR mice by Western-blot analysis were higher than those of normal control group(t=3.35, P < 0.05), While these of PEDF treatment group showed a considerable decline in comparison with PBS treatment control group (P < 0.01), and there were no difference in normal control group and PEDF-treated group (F=11.764, P > 0.05). Similarly, expression levels of IL-1β mRNA tested by Real-time RT-PCR were obviously increased in the OIR model group when compared to normal control group(t=4.43, P < 0.01). After treated with PEDF, expression levels of IL-1β mRNA showed a considerable decrease when compared to PBS treatment control group (P < 0.01), and there were no difference in normal control group and PEDF-treated group (F=11.15, P > 0.05). ConclusionsPEDF can inhibit oxygen-induced retinal neovascularization. The mechanism may be related to that PEDF can downregulate the expression of IL-1β in retina.