title: Growth-related effects of oxidant-induced stress on cultured RPE and choroidal endothelial cells.
abstract: Mounting evidence suggests that oxidative stress caused by reactive oxygen intermediates is a significant mechanism in the pathogenesis of age-related macular degeneration (AMD). Although vascular endothelial growth factor (VEGF) and other cytokines are involved in choroidal neovascularization (CNV) it is largely unknown whether oxidative stress may predispose the eye to increased levels of proangiogenic factors. In an in vitro study we have determined viability and proliferation of both human retinal pigment epithelial (RPE) cells and bovine choroidal endothelial cells (CECs) and assessed the release of basic fibroblast growth factor (bFGF) and VEGF from RPE cells after exposing them to oxidative stress. Permanent presence of tert-butyl-hydroperoxide (tBH), a pro-oxidative stressor, in the cell cultures resulted in decreasing viability and proliferation of RPE cells and CECs. Loss of RPE cell viability was associated with activation of apoptosis by tBH in a dose-dependent manner. The antioxidant, N-acetyl-L-cysteine (NAC), and secreted soluble mediators of RPE cells were appropriate to attenuate the effects of tBH-mediated oxidative stress. RPE cells exposed to tBH were found to release increasing amounts of bFGF but not VEGF after 24h of culture, thereby supporting proliferation of CECs. These findings suggest that oxidative stress compromises the viability of RPE cells and CECs. However, increased bFGF levels concomitantly released from RPE cells may attenuate the CEC-directed effect, protect CECs from oxidative insults, and are likely to promote CNV.
authors.affiliation: University of Leipzig, Eye Hospital, Liebigstrasse 10-14, D-04103 Leipzig, Germany. eichwolf@rz.uni-leipzig.de
authors.forename: Wolfram
authors.initials: W
authors.lastname: Eichler
authors.forename: Anett
authors.initials: A
authors.lastname: Reiche
authors.forename: Yousef
authors.initials: Y
authors.lastname: Yafai
authors.forename: Johannes
authors.initials: J
authors.lastname: Lange
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002829:Choroid / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006801:Humans; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D043925:Angiogenesis Inducing Agents; D016877:Oxidants; D016222:Fibroblast Growth Factor 2; D004247:DNA; D020122:tert-Butylhydroperoxide