98th Annual Meeting DOG 2000

P 13

Intravitreal application of gentamycin induces drusen-like RPE-changes in Wistar rats

T. T. Luther, J. F. Jordan, G. Thumann, S. Grisanti , P. Esser, U. Schraermeyer

Introduction: To date the pathogenesis of drusen formation in age related macular degeneration is not fully understood. There is evidence of contribution of sequestered RPE cell cytoplasm in the composition of drusen apart from various amorphous materials. The origin of these cell remnants, however, is controversial. Furthermore there are few animal models, exhibiting drusen in their phenotyp. The aim of this study was to investigate the influence of an intravitreal injection of aminoglycoside on retinal morphology in a small animal, which is straightforward to handle and to study in a laboratory environment.

Methods: Wistar rats 12 months of age were treated with a one dose application of 5 µl Refobacin (400 µg) intravitreally via the pars plana. Ninety days after treatment the animals were killed by CO2 anaesthesia and eyes were enucleated. Sections were prepared for studies using light and electron microscopy.

Results: In light microscopy sections areas of RPE cells with disrupted plasma membranes, ballooned nuclei and discoloured cytoplasm were seen. These regions were overgrown by adjacent RPE cells, thus forming a RPE duplication. Moreover the connection of RPE with neighbouring photoreceptor outer segments was less stable. Generally there was vascular overfilling in the choriocapillaris. No signs of inflammation with invasion of cells of the immune system were noted. In electron microscopy accumulation of cell organelles like nuclei and mitochondria in areas of RPE duplication was clearly visible. Phagosomes or lipid granula, however, could not be demonstrated in the outer RPE cell layer.

Discussion: In this study RPE changes could be induced by intravitreal application of gentamycin, which are related morphologically to signs of drusen formation. We hereby present a rat model for further investigation of drusen like structures in the RPE. This is the first description of RPE duplication in an animal model. The results of this study might lead to further insight into the early stages of drusen development in human age related macular degeneration.

University Eye Hospital Cologne, Joseph-Stelzmann-Str. 9, D-50931 Cologne