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Max Brinkmann, Eva Dietrich, Franziska Köhler, Salvatore Grisanti, Martin Rudolf, Mahdy Ranjbar; Effects of apolipoprotein A-I mimetic peptide 4F on human RPE cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1994. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Oxidized (ox) low-density lipoprotein (LDL) may contribute to the pathogenesis of age related macular degeneration (AMD). It has been shown that oxLDL decreases cell viability of the retinal pigment epithelium (RPE) and induces the release of proinflammatory and proangiogenic factors from the RPE. The apolipoprotein A-I mimetic peptide L-4F has been shown to be effective in remodeling Bruch’s membrane. In this study, we investigated the effects of L-4F on RPE cells and evaluated whether it can be used to protect them from oxidative harm.
Human RPE cells (ARPE-19) were cultured for 48h and then treated with L-4F (100µg/ml) for 24h in absence or presence of oxLDL (50µg/ml, 100µg/ml). The culture medium was then replaced by fresh one (without L-4F or oxLDL) and after another 24 hours of incubation the cells were fixed and stained. The supernatant was collected separately. Immunofluorescence staining was performed against oxLDL, TNF-α and VEGF-A. The supernatant was analyzed by ELISA for various angiogenic factors. Finally we performed a cell migration assay to further evaluate the influence of oxLDL and L-4F.
While low concentrations of oxLDL significantly increased the expression/release of proangiogenic/proinflammatory factors from RPE cells and improved migratory response, higher concentrations of oxLDL led to decreased cell viability. This effect could be significantly reduced by L-4F.
The apolipoprotein A-I mimetic peptide L-4F seems to be a potential drug candidate to treat the underlying mechanisms of age-related macular degeneration. Further studies are needed to reproduce a biologically relevant protective effect in vivo.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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