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S. Peters, K.–.U. Bartz–Schmidt, U. Schraermeyer; Inhibiting Lysosomal Function in RPE Cells Leads to Exocytosis of Residual Bodies at the Basolateral Plasma Membrane . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3503.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Chloroquine, a drug used in anti–malaria therapy, causes damage in cells with high proteolytic activity like the retinal pigment epithelium (RPE). This is due to its inhibiting effects on lyososomal degradation pathways. The aim of our study was to analyze morphological changes in the RPE and Bruch’s Membrane (BM). Methods: Long Evans rats were injected intraperitoneally with 50 mg/kg chloroquine twice a week for 6 weeks. After enucleation, the retina–choroid complexes were analyzed morphologically by electron microscopy. Results: Apart from the presence of incompletely digested phagosomes in the RPE cells, we observed widely enlarged intercellular spaces in the RPE, containing residual material between the junctions of RPE cells and BM. Residual material originating from phagosomes was released from the RPE cells into these vacuoles. Debris accumulated within BM and encircled choriocapillaris endothelial cells. Conclusions: Here we show for the first time the exocytosis of undegraded phagocytic material into the enlarged intercellular spaces between adjacent RPE cells and into the basal labyrinth, following inhibition of lysosomal degradation. This material is supposed to originate from insufficiently degraded photoreceptor outer segments. Electron dense deposits in BM and choriocapillaris in addition to oxidative stress caused by lysosomal dysfunction are likely to reduce oxygen– and nutrition–flow from choriocapillaris into the retina.
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