Familial exudative vitreoretinopathy (FEVR) is a serious hereditary retinal vascular disease. The clinical manifestations vary, and the severity of the patients' condition is different. In severe cases, it may lead to bilateral blindness. The pathogenic mechanism of FEVR is also complex. At present, more than ten classical and candidate pathogenic genes have been found: NDP, FZD4, LRP5, TSPAN12, CTNNB1, KIF11, ZNF408, RCBTB1, LRP6, CTNNA1, CTNND1, JAG1, ATOH7, DLG1, DOCK6, ARHGP31 and EVR3 region. These pathogenic genes are involved in Wnt/β-catenin signaling pathway, norrin/β-catenin pathway and Notch pathway. They regulate and affect the development of retinal blood vessels, hyaloid vascular system regression, endothelial cell connections, and blood retinal barrier homeostasis, ultimately leading to the occurrence and development of FEVR disease.
An experimental model of proliferative vitretinopathy(PVR) induced by macrophages was used for the evaluation of drug efficacy of daunomycin encapsulated in liposomes in the treatment of PVR.Five mu;g daunomycin(n=40),10mu;g daunomycin-liposome(DL,n=30)and 0.1 ml saline or empty liposomes(n=40,as controls)were injected into the rabbit vitreous after macrophage injection.Retinal detachment developed in 77.5% of the control eyes on day 28,compared to 33.3% of the eyes treated with DL(P＜0.01)and 50% of the daunomycin-treated eyes(P＜0.05).The results suggest that encapsulation in liposomes of cytotoxic agents can enhance drug efficacy.The phasic course of development of PVR is important in the selection of particular drugs. （Chin J Ocul Fundus Dis,1993,9:77-80）
Our previous experiments showed limited results of treatment with daunomycin when given at the inflammatory stage of proliferative vitreoretinopathy(PVR)induced by macrophages in rabbits.In the present study,we observed the inhibition of intraocular cellular proliferation in the same model by daunomycin which was injected in a dosage of 5mu;g 6 days after intravitreal macrophage injection,with 3H-thymidine autoradiography.The efficacy of daunomycin was also compared with that of triamcinolone,and combined triamcinlone and daunomycin.The retinal detachment occurred in 33.3%,16.1%,8.3%and 83.3%(P＜0.01) of the eyes treated with daunomycin,triamcinolone,combined drugs and the control groups,respectively.Autoradiography revealed a singnificantly decreased number of labelled nuclei of proliferative cells on days 7 and 14 in daunomycin-treated eyes(compared to controls,18.8plusmn;3.2 vs 35.7plusmn;3.4;52.1plusmn;8.0 vs 81.3plusmn;14.6，P＜0.01,respectively).Significantly decreased numbers of inflammatory cells and labelled cells were also noted in eyes treated with triamcinolone and combined drugs.The results suggest that daunomycin given at the proliferative stage,and triamcionlone given at the inflammatory stage of PVR,or combined drugs can prevent traction retinal detachment. （Chin J Ocul Fundus Dis,1994,10:229-231）
Objective To investigate the occurrence, progress and conversion of hypotony in anterior proliferative vitreoretinopathy (aPVR), and to provide knowledge about how to prevent and treat it． Methods Animal models of chronic hypotony by aPVR were made with cultured ho mologous dermal fibroblasts on pigmented rabbits．The intraocular pressure (IOP) and ultrasound biomicroscopy(UBM) examination were taken preoperatively and on days 7,14, 28 and 56 postoperatively．Rabbits were killed on days 14, 28 or 56 postoperatively, prepared for histology and ultrastructure examination． Results The average IOP of experimental group was lower than that of control group on days 7,14,28 and 56 significantly (Plt;0．01)．UBM demonstrated that trip like echo emerged in front of ciliary body four weeks postoperatively, and tractional retinal detachment was found four weeks and eight weeks postoperatively in experimental group． Microscopic examination showed atrophy orabsence of the non-pigmented ciliary epithelium on days 28 and 56 postoperatively in experimental group．Electronic microscopy showed that the amount of mitochondrions decreased and there were many vacuoles in the non-pigmented ciliary epithelium in experimental group four and eight weeks postoperatively． Conclusions Atrophic change of the non-pigmented epithelium due to dragging effect of the ciliary body from the epiciliary membrane in aPVR might be the main cause of hypotony． (Chin J Ocul Fundus Dis, 2001,17:216-220)
The stimulating effects of subretinal fluid (SRF) of 31 patients with rhegnmtoganous retinal detachment (among them 5 are recurrent) on the growth of fihroblasts were investigated. The results demonstrated that all samples of SRF showed stimulating effect in a variable degree.The range of proliferation-stimulating activity was from 86. 7% to 366.7% above the baseline.The stimulating ahility was mainly related to the degree of PVR and may be also related to the extent and clinical course of the detaehrnent. When stimulating rate was S0Y0 ,the dilution multiple of SRF was higher in recurrent patients than that in initiate ( P＜0.01). （Chin J Ocul Fundus Dis,1993,9:11-13）
ObjectiveTo observe and analyze the genotype and clinical phenotype in 34 families of familial exudative vitreoretinopathy associated with (FEVR) gene variation.MethodsCohort study. Thirty-four FEVR families, in which the patients and both of their parents were all found to have FEVR-related gene mutations (proband 34 cases, 67 eyes; parents 68 cases, 136 eyes), were included in the study. These patients were identifIed from 722 FEVR patients through genetic screening, which diagnosed in Department of Ophtalmology of Xinhua Hospital and Tianjin Medical University Eye Hospital from January 2010 to December 2018. The probands and their parents underwent a comprehensive ophthalmological examination appropriate to their age, including BCVA, intraocular pressure, axial length, slit lamp examination, indirect ophthalmoscopy, FFA or color fundus photography or wide field color fundus photography. According to the severity of the disease, the clinical manifestations were divided into severe phenotype and mild phenotype. Thirty-four normal healthy people over 40 years old were included as the control group. The peripheral blood samples of FEVR family members and control group members were collected, and the genes known to be involved in FEVR, such as FZD4, LRP5, NDP, TSPAN12, ZNF408 and KIF11, were analyzed by next generation sequencing molecular genetics. The data were statistically analyzed by SPSS. The counting data was expressed in numbers or rates, and tested by Kruskal-Wallis test and χ2 test to find out the existence of significant difference.ResultsIn 67 eyes of the 34 probands, 48 eyes (71.64%) were classified into severe phenotype and 19 eyes (28.36%) were mild phenotype. In 136 eyes of 68 parents of the proband patients, 76 eyes (55.88%) were normal, 60 eyes (44.12%) were classified into mild phenotype, and no severe phenotype was found. A total of 65 variants of FEVR-related genes were detected in the 34 probands, of which LRP5 mutation was the most common (64.61%), followed by FZD4 (12.31%), NDP (10.77%), TSPAN12 (6.15%), ZNF408 (4.62%) and KIF11 (1.54%). Missense mutations were the most common variant in FEVR-related genes. However, the results of correlation analysis indicated that there was no significant correlation between the type of mutation and the severity of clinical phenotype (H=1.775, P=0.620). Among the 65 mutation types, 21 types have been previously identified and 44 were novel in this study. Thirty-nine eyes of 20 cases had only one single pathogenic mutation gene but with multiple mutation sites, 26 eyes of 13 cases carried 2 relevant pathogenic mutation genes, and 2 eyes in one case had 3 pathogenic mutation genes. The mutation frequencies of LRP5, NDP, ZNF408, FZD4, TSPAN12 and KIF11 genes in probands were significantly higher than those in control group, and the difference was statistically significant. The total mutation frequencies of LRP5, NDP, ZNF408, FZD4, TSPAN12 and KIF11 genes in proband group were significantly higher than those in control group (χ2=64.702, P＜0.001).ConclusionsIn the FEVR families, the most frequent mutations were those in LRP5, followed by FZD4, NDP, TSPAN12,ZNF408 and KIF11. Missense mutation is the most common type of FEVR-related gene mutation, but there is no significant correlation between the clinical phenotype and gene variation type. Most of the probands were with severe clinical phenotype, while most of the parents with FEVR pathogenic gene mutation showed normal or mild manifestations.
Objective To investigate the effects of genistein with different concentration on proliferation and apoptosis of cultured human retinal pigment epithelial (RPE) cells in vitro. Methods The effect of genistein with the concentration of 5，10，25，50，75，and 100 mg·L-1on the proliferation of cultured RPE was examined by tetrazolium salt (MTT) assay and AgNORs staining. The cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) methods, in the mean time, the morphologic changes of cell apoptosis were observed by light microscopy and transmission electronic microscopy, the results of which were compared with the normal RPE cells. Results Genistein with the concentration of 25, 50, 75, and 100 mg·L-1had a dose-dependent and time-dependent antiproliferative effects on RPE cells with the inhibitory rate of 12.0%-64.6% (P＜0.05). The results of AgNORs staining showed that the number of AgNORs in the nucleolus decreased when treated by genistein. In TUNEL staining, the median of percent of apoptotic RPE cells was 7.6%, 9.8%, 13.7% when treated with 50 mg·L-1genistein, 10.3%, 16.4%, 23.4% when treated with 75 mg·L-1genistein, and 15.4%, 21.2%, 35.8% when treated with 100 m g·L-1genistein respectively for 24, 48, and 72 hours. After the treatme nt with 50 mg·L-1genistein for 48 hours, the apoptosis in the nucleolus of RPE cells was found. Conclusions Genistein with different concentrations has a dose-dependent and time-dependent antiproliferative effect on RPE cells. Genistein can induce the apoptosis of RPE cells when it reaches a certain extent of concentration. (Chin J Ocul Fundus Dis，2004，20：241-244)
Objective To evaluate the anatomical and functional results of retinotomy in treatment of complicated retinal detachment. Methods Twenty-three eyes were treated with retinectomy during vitrectomy for complicated retinal detachment with proliferative vitreoretinopathy when complete reattachment of retina was not obtained despite careful mambrane peeling. After released the peripheral vitreoretinal contraction or pulled subretinal membranes, perfluorocarbon liquid injection, laser retinopexy and silicone oil tamponade were performed. Retinotomy size ranged from 30-degree to 360-degree (average 132-degree). Results Retinal attachment were obtained in all of the operated eyes at the end of the operation. Silicone oil was removed from 15 eyes (65．0%) within 3～11 months postoperatively. After a minimum follow-up of 6 months, the retinae were completely attached in 17 eyes ( silicone oil was not removed in 4 eyes ) and visual acuity of 0.02 or better was obtained in 11 eye (48．0%). Recurrent retinal detachment occurred in 2 eyes in which the silicone oil had been removed. The major complications were recurrence of the proliferation in 6 eyes (26．0%) and hypotony in 3 eyes (13．0%). Conclusion Retinotomy is beneficial to reattach the retina for eyes with advanced proliferative vitreoretinopathy in seemin gly inoperable cases. (Chin J Ocul Fundus Dis,2001,17:87-89)