Investigations of RPE Cells of Choriodal Neovascular Membranes from Patients with Age-Related Macula Degeneration

Abstract

Age-related macular degeneration (AMD) is the most frequent cause for blindness in older age. The most severe complication is the development of choroidal neovascularisation (CNV). The retinal pigment epithelium (RPE) plays an important role in the induction of angiogenesis in AMD (Glaser et al., 1985; Young, 1987; Morse et al., 1989; Bird, 1991) by secreting the majority of angiogenic factors (Kliffen et al., 1997). The most important angiogenic factor is VEGF (vascular endothelial growth factor). CNV membranes contain high amounts of VEGF and it is known that overexpression of VEGF in the RPE leads to choroidal neovascularisation (Schwesinger et al., 2001). In vitro and in situ investigations revealed several extracellular stimuli inducing secretion of angiogenic factors by the RPE. A major part takes a hypoxia-comparable situation in the area of soft drusen (Eagle, 1984). In consequence to this, VEGF and factors inducing the VEGF production are secreted by the RPE and the neuronal retina (D' Amore, 1994; Shima et al., 1995; Stone et al., 1995; Frank et al., 1996; Kliffen et al., 1997; Tanihara et al., 1997). VEGF secretion is stimulated by advanced-glycation endproducts (AGE) accumulating in CNV membranes, and also by vitronectin, the major extracellular matrix component in drusen (Hammes et al., 1996; Hageman et al., 1999). In addition, insulin-like growth factor-1 (IGF-1) secreted by the neuronal retina and tumour necrosis factor-a (TNFa) secreted by macrophages which migrate towards the retina during the development of the first blood vessels are known to induce VEGF secretion by RPE cells (Punglia et al., 1997; Oh et al., 1999).