ObjectiveTo observe and classify the characteristics of optical coherence tomography (OCT) for several common diseases which could lead to submacular choroidal neovascularization (CNV), and to provide the warrant to make the differential diagnosis and treatment of CNV.MethodsThe data of OCT of 165 patients (187 eyes) with CNV due to AMD, CEC, high myopia and ICNV diagnosed by fundus photography and fundus fluorescein angiography (FFA) were retrospectively analyzed, and the images of OCT were classified considering the results of FFA, and the characteristics of different types of the images were sumerized.ResultsWell-defined fusiform thickening of retinal pigment epithelial (RPE) and choriocapillary layer in CNV with well-defined border (60 eyes), dispersed backscattering increase in poorly-defined CNV (101 eyes), optic darkspace beneath RPE layer in serous detachment of RPE layer (19 eyes), quickly decreased high backscattering region under RPE layer in hemorrhagic detachment of RPE layer (11 eyes), slight to moderate backscattering region between RPE layer in fibrovascular detachment of RPE layer (10 eyes), and detachment of neurepithelial layer from RPE layer with the optic darkspace between the layers in detachment of neurepithelial layer (45 eyes) were observed.ConclusionsThe images of OCT for the common diseases which could lead to submacular choroidal neovascularization may be divided into 6 types. Analyzing the characteristics of images of OCT is helpful in differential diagnosis and treatment of CNV. (Chin J Ocul Fundus Dis, 2005,21:69-73)
Objective o observe the expression of Notch1 and Delta-like ligand 4 (Dll4) on the fibrovascular membranes in proliferative diabetic retinopathy (PDR), and investigate its relationship with vascular endothelial growth factor receptor 2 (VEGFR2). Methods Fifty-seven PDR patients (60 eyes) who underwent vitrectomy were enrolled in this study. The PDR patients were divided into non-injection group (30 patients, 32 eyes) and injection group (27 patients, 28 eyes). The eyes in injection group received intravitreal injection with ranibizumab at 2 to 7 days before surgery. The preretinal fibrovascular membranes were obtained from the PDR patients during vitrectomy. Eighteen epiretinal membranes were obtained from the non-diabetic patients was served as controls. The real-time polymerase chain reaction (RT-PCR) and immunohistochemical methods were used to detecting the expression of Notch1, Dll4 and VEGFR2. In the meantime, the numbers of the nucleus of vascular endothelial cells in the membranes stained with hematoxylin were counted. Results The immunohistochemical staining revealed that there were positive expression of Notch1, Dll4 and VEGFR2 in all PDR membranes, regardless of the injection of the ranibizumab. The levels of Notch1, Dll4 and VEGFR2 protein in non-injection group were higher than those of injection group (t=3.45, 6.01, 4.08;P=0.030, 0.008, 0.023). In injection group, the number of endothelial cells in the membranes reduced (17.17±2.48) compared with that of the non-injection group (41.50±5.57). There was significant difference in the number of endothelial cells in the membranes between the two groups (t=9.58,P＜0.05). RT-PCR showed that the differences of the mRNA expression of Notch1, Dll4 and VEGFR2 were all statistically significant among the PDR group and control group (H=12.50, 12.50, 12.02;P＜0.05).The expression of Notch1, Dll4 and VEGFR2 in the PDR membranes was higher than that of epiretinal membranes from non-diabetic patients. In the PDR group, the expression of Notch1, Dll4 and VEGFR2 of non-injection group was higher than that of injection group. Spearman correlation analysis showed that the expression of mRNA between VEGFR2 and Dll4 (r=0.83), VEGFR2 and Notch1 (r=0.81), Notch1 and Dll4 (r=0.87) were all significantly correlated (P＜0.05). Conclusions The expression of Notch1 and Dll4 in the PDR membranes are higher than that of the control group, and it is positively correlated with the expression of the VEGFR2. Notch1 and Dll4 play a regulatory rule in the neovascularization in PDR, the acting way may be correlated with VEGFR2.
Objective To investigate the role of adenosine A2A receptor plays in retinal pathological neovascularization in mice. Methods A total of 202 mice were divided into room-air group (n=66) and oxygen induced retinopathy (OIR) group (n=136). Among room-air group, there were 18 A2A knock-out (KO) mice (KO subgroup) and 24 C57BL/6 mice as wide type (wide type subgroup). OIR group were divided into OIR control subgroup (n=48), A2A-OIR subgroup (n=24) and Caffeine-OIR subgroup (n=64). The retinal neovascularization of OIR group was induced by oxygen. The pathological neovascularization was determined by retinal sections. Fluorescent quantitative polymerase chain reaction (PCR) was used to measure the mRNA expression of A2A and vascular endothelial growth factor (VEGF). 0.1, 0.3, 1.0 g/L Caffeine was dissolve in drinking water of lactating females in Caffeine-OIR subgroup, non-perfusion areas of retina in mice at the age of 0 - 17, 0 - 7, 7- 17, 7-12, and 12- 17 days were analyzed in different dosage and when the dosage as 1.0 g/L. Results Compared with OIR control subgroup, the retinal non-perfusion areas and the numbers of endothelial cell nuclei breaking through the internal limiting membrane in A2A- OIR subgroup were reduced significantly (t=7.694, 7.747;P＜0.001). Compared with wide type subgroup, the level of A2A and VEGF mRNA in OIR control subgroup increased significantly (t=4.036, 2.230;P＜0.05). Compared with OIR control subgroup, the level of VEGF mRNA in A2A- OIR subgroup decreased significantly (t=3.122,P＜0.01). Compared with OIR control subgroup, the retinal non-perfusion areas in mice at the dosage of 0.1 and 1.0 g/L (t=2.397, 4.533) and at the age of 0 -17, 0 -7 days when the dosage as 1.0 g/L (t=4.070, 2.399) were reduced significantly (P＜0.05). Conclusions The expression of adenosine A2A receptor increases in oxygen-induced retinal pathological neovascularization. Adenosine A2A receptor may regulate the expression of VEGF. A2A receptor inactivation can inhibit oxygen-induced retinal pathological neovascularization.
Objective To determine the expression of the growth factors and the receptors related to angiogenesis in the intraocular tissues incarcerating in the sclerotomy sites. Methods Ten specimens from prolapsing intraocular tissues in sclerotomy sites during vitrectomy were obtained and serially sectioned in cryostate and were stained with a group of polyclonal antibodies against vascular endothelial growth factor(VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-A(PDGF-A) and transforming growth factor-β1(TGF-β1) as well as their receptors by using a streptavidin peroxidase system. Results The tissues prolapsed from the sclerotomy sites were identified as retina(3 cases), vitreous tissues(3 cases), degenerated red blood cell components(2 cases), ciliary body(one case) and fibrous tissue(one case). All specimens expressed VEGF and bFGF as well as their receptors. PDGF-A, TGF-β1 and their receptors expressed in the most of specimens. The positive cells included retinal cells, ciliary non-pigmented epithelial cells and pigmented epithelial cells, fibrous cells and the cells in vitreous. Conclusions The intraocular tissues incarcerated in the sclerotomy entries express the growth factors and receptors related to angiogenesis. This might be one of the potential factors of developing anterior proliferative vitreoretinopathy. (Chin J Ocul Fundus Dis, 2002, 18: 34-37)
Objective To determine whether kringle 4-5 could inhibit choroidal neovascularization (CNV) in mice induced by argon laser photocoagulat ion. Methods Fundus laser photocoagulation was performed on C57BL/6J mice to induce CNV. In treatment group, 20 μg (low dosage group) and 50 μg (high dosage group) kringle 4-5 were injected retrobulbarly after photocoagulation. In control group, equilibrium liquid was injected retrobulbarly. Choroidal neovascularization was evaluated on the 7th and 14th day after photocoagulation by fundus fluorescein ang iography. The mice were killed on the 14th day after photocoagulation, the lesions were evaluated histologically and immunohistochemically, and the expression of CD105 was detected. The Expression of VEGF and bFGF was detected by immunohist ochemistry on the 4th day after photocoagulation.Results The incidence of CNV was 64.3% in control group, 51.2%（P＜0.05）in low dosage group, and 44. 1% (P＜0.01) in high dosage group. The CNV lesions were smaller in kringle 4-5 injected eyes in a dose-dependent manner and the number of proliferative vascular endothelial cells in the subretinal membrane of the treated eyes was smaller than that of the control eyes. There was no significant difference of the expression of VEGF and bFGF between the mice in control and treatment group.Conclus ions Kringle 4-5 could inhibit the development of choroidal neovascularization in the experimental mice model.(Chin J Ocul Fundus Dis，2003，19：201-268)
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)
Choroidal neovascularization is the leading causes of central vision loss in wet age-related macular degeneration (wAMD) patients. Smoking not only aggravates the incidence and severity of the choroidal neovascularization of wAMD, but also affects the clinical treatment, making the prognosis worse. Nicotine, as an important harmful substance in tobacco, is an easily addictive and highly toxic alkaloid. Animal experiments and clinical studies have confirmed that nicotine can aggravate wAMD by mediating angiogenesis through nicotinic acetylcholine receptor, bone marrow blasts, inflammation, complement system, etc. Therefore, in order to early take appropriate intervention measures to prevent and delay the development, we should actively explore the exact pathogenesis by which nicotine aggravates the choroidal neovascularization.