gms | German Medical Science

The retinal pigment epithelium (RPE) is close interaction partner of the photoreceptors. In this interaction both the RPE and the photoreceptors form a functional unit. In this way mutations of gene expressed in the photoreceptors can lead to primary RPE degeneration and vice versa. In this interaction the RPE fulfills the following tasks: light absorption, transepithelial transport, ion buffering in the subretinal space, visual cycle, phagocytosis of daily shed tips of photoreceptor outer segments, secretion and immune modulation. The change or loss of one of these functions can lead to retinal degeneration among them are retinitis pigmentosa, hereditary forms of macular degeneration or age-dependent macular degeneration. Thus the RPE is in the center of many therapeutic approaches to prevent retinal degeneration. In these therapeutic approaches either the disease-depending loss of RPE cells or the disease-leading loss or change in RPE function is corrected. The loss of RPE cells can be corrected by transplantation of stem which cells which have been differentiated into RPE cells. This in the animal model proven method is currently in the phase I clinical trial. In the investigation of the possibilities of gene therapeutic approaches it was found that the RPE is easily accessible for gene manipulation. Therefore, the first successful trial of the gene therapy of a monogenetic disease worldwide was developed for the correction of a gene defect in the RPE. This was successfully proven in a dog model for Leber’s congenital amaurosis and is now in phase II clinical trial. Furthermore, the gene therapeutic approach to treat choroidal neovascularisation aims the change of the secretory behavior of the RPE. Using a transgene for the anti-angiogenic factor PEDF the neovascularisation is decreased in the animal model. This approach is currently in phase I clinical trial.