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增殖性玻璃体视网膜病变细胞增殖与凋亡的信号传导途径研究 |
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增殖性玻璃体视网膜病变细胞增殖与凋亡的信号传导途径研究 |
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作者:张新媛, … 文章来源:北京首都医科大学附属北京同仁医院眼科中心 100730 点击数:1340 更新时间:2004/6/25
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Purpose: To assess the incidence of cell proliferation and apoptosis in epiretinal membranes from eyes with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), and macular pucker (MP) and to further investigate the potential involvement of key executors of apoptosis.
Methods: Epiretinal membranes were obtained from the eyes of twenty-three patients who underwent vitrectomy surgery for recurrent retinal detachment due to PVR (n=16), traction retinal detachment due to PDR (n=5), and macular pucker (n=2). Cell proliferation was evaluated by Ki-67 and PCNA (proliferation cell nuclear antigen) immunostaining. Apoptosis was assessed by TUNEL (terminal deoxynucleotidyl transfrase-dUTP-nick end labeling). The expression of caspase-3 and PARP (poly-ADP-ribose-polymerase) were detected using the antibodies against activated caspase-3 and p85 fragment of PARP. Cytokeratin and activated caspase-3/ PARP, GFAP (glial fibrillary acidic protein) and activated caspase-3/PARP double staining were used to identify cell types in the membranes.
Results: There was no statistically significant difference in the cell PI (proliferative index) between PVR (82.1±4.2), PDR (70.1 ±7.3), and macular pucker (72.9±22.8) by multivariate analysis (P=0.39, ANOVA) and univariate analysis. Apoptotic nuclei were seen more frequently in chronic retinal detachments of greater than two months duration but the difference compared to shorter term retinal detachments was not statistically significant (P=0.19). The AI (apoptosis indices ) determined for PVR (2.3±0.7), PDR ( 3.4±1.5) and macular pucker (5.5±3.2) were not significantly different (ANOVA, P=0.41). Apoptotic nuclei were correlated increased with expression of caspase-3 and PARP. Many apoptotic cells appeared to derive from retinal pigment epithelium cells.
Conclusions: Cell proliferation and apoptosis appear to be key mechanisms regulating certain cell populations in epiretinal membranes of PVR, PDR and macular pucker. Inhibition of proliferative regulators such as PCNA and/or activation of apoptotic executors such as caspase-3 may serve as therapeutic targets to halt progression of proliferative retinal disorders. |
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