ObjectiveTo reveal the pathogenic mutation in a three-generation Chinese family with autosomal dominant familial exudative vitreoretinopathy (FEVR). MethodsThree patients and a healthy spouse from the index family with FEVR were recruited. The proband was a 5 years old boy. His mother and grandpa were presented with typical FEVR presentations, while his father with normal ocular fundus. DNA was extracted from peripheral blood samples taken from all four participants. All coding and exon-intron boundary regions of five targeted genes, including NDP, FZD4, LRP5, TSPAN12 and ZNF408 were amplified with polymerase chain reaction and sequenced using direct sequencing. In silico analyses were applied to determine the conservation of the mutation site, pathogenic effect and the potential protein crystal structural changes caused by the mutation. ResultsFZD4 c.478G > A, a susceptible mutation was found after four high frequency mutation sites which MAF values were higher than 0.001 was filtered among 5 single nucleotide variations detected in four participants, leading to the residue 160 changing from glutamate to lysine (p.E160K). Co-segregation analysis between genotypes and phenotypes revealed FZD4 p.E160K as the disease-causing mutation for this family. Conservational analysis suggested that this mutation site was highly conserved among all tested species. Functional analysis predicated that this mutation may be a damaging mutation. Crystal structural analysis also indicated that this mutation could lead to the elimination of the hydrogen bond between residue 160 and asparagine at residue 152, thus altering the tertiary structure of the protein and further impairing the protein function. ConclusionOur study demonstrates FZD4 p.E160K as a novel pathogenic mutation for FEVR.
Purpose To investigate the expression of the interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-alpha;) in epiretinal membranes(ERM) of eyes with proliferative vitreoretinopathy(PVR). Methods Nineteen epiretinal membranes were obtained form eyes undergoing vitrectomy for retinal detachment complicated with PVR and observed by immunohistochemical methods. Results Expression of IL-6 and TNF-alpha; were observed in 12 and 15 membranes respectively with positive staining mostly in extracellular matrix of epiretinal membranes.Only one membrane showed positive to IL-6 intracellularly,and expression for IL-6 and TNF-alpha; simultaneously in membranes. Conclusion The findings indicate that IL-6、and TNF-alpha;might be involved in the development of PVR. (Chin J Ocul Fundus Dis,1998,14:219-221)
Retinal macrophages and (or) microglial cells play important roles in regulating inflammation, angiogenesis and tissue repairing, thus affect the development and prognosis of ischemic retinal disease, ocular immune diseases and ocular tumors. Reversing the polarization imbalance of these cells may provide new therapeutic strategies for ischemic retinal disease and ocular immune diseases. The duality of the polarization direction of these cells is still controversial in the inflammatory reaction and pathological angiogenesis of ischemic retinal disease. Meanwhile, the plasticity and diversity of the function need to be further studied and discussed.
Objective To investigate the relationship of clinical indexes between retinopathy in systemic-lupus-erythematosus （SLE）nephritis and SLE，and to discuss its clinical significance. Method The clinical data of 43 cases of SLE nephritis with ocular fundus diseases were retrospectively analyzed.The relationships between retinopathy and kidney defect，general lesions，SLEDAI grade，antinuclear antibody （ANA），anti-double stranded DNA，complement 3 and antiphospholipid antibodies were analyzed with Logistic regression respectively. Results In 86 eyes of the43paitents，there were retinal cotton wool spots in51eyes（59.3%），edema of optic disk in 43 eyes（50.5%），retinal haemorrhage in 12 eyes（14.0%），retinal artery occlusion in 5 eyes（5.8%），central retinal vein occlusion in 2 eyes（2.3%），retinal detachment in 3 eyes（3.5%），optic atrophy in 2 eyes（2.3%），and neovascularization in 2 eyes（2.3%）.Logistic regression analysis revealed that SLEDAI grade had linear dependent relation with cotton wool spots and optic disk edema（chi;2=42.154，6.498;P＜0.001），and didnrsquo;t have any correlation with proteinuria，hematuria and kidney function.Linear relation between retinal vascular occlusion and antiphospholipid antibodies was found（chi;2=24.475，P＜0.001）.Retinal haemorrhages，retinal detachment，optic atrophy and neovascularization did not correlate with clinical features. Conclusion SLEDAI grade had linear dependent relation with cotton wool spots and optic disk edema in patients with SLE nephritis，and Linear relation between retinal vascular occlusion and antiphospholipid antibodies is ascertained. Ocular fundus diseases are clinically important for evaluating the therapeutic responses and prognosis in lupus nephritis. (Chin J Ocul Fundus Dis, 2006, 22: 239-241)
Purpose To investigate the expression of intercellular adhesion molecules ICAM-1 and Mac-1，in epiretinal membanes (ERM) of eyes wi th proliferative vitreoretinopathy (PVR)． Methods Twenty epiretinal membranes were obtained from eyes undergone vitrectomy for retinal detachment complicated with PVR and observed by immunohistochemical examination． Results Expressions of ICMA-1 and Mac-1 were observed in 18 and 15 membranes respectively．Expression of both adhesion molecules in 12 membranes． Conclusion The findings indicate that adhesion molecules might be involved in the development of PVR． (Chin J Ocul Fundus Dis，2000，16：71-138)