Apoptosis and cell proliferation in proliferative retinal disorders: PCNA, ki-67, caspase-3, and PARP expression

作者：Zhang XY; Barile G^*; Chang S; Hays A; Pachydaki S; Schiff W; Sparrow J

来源：Current Eye Research, 2005, 30(5): 395-403.

DOI：10.1080/02713680590956306

• apoptosis
• cell proliferation
• macular pucker
• proliferative diabetic retinopathy
• proliferative vitreoretinopathy

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 23 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) was detected using 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 proliferative index between PVR (70.1 +/- 4.2%), PDR (82.1 +/- 7.0%), 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 2 months duration, but the difference, compared to shorter term retinal detachments was not statistically significant (p = 0.19). The 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.

• 出版日期2005-5