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M. Brankov, D. Zhang, T. Robertson, E.P. Rakoczy; Cathepsin D Mutations Associated with Retinal Dystrophy in Transgenic Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1702.
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Purpose:The aim of this work is to clarify the effects of inactive CatD or proCatD on POS-debris accumulation in RPE that is supposed to cause retinal degeneration or AMD. A transgenic model with the inactive human CatD (CatDM1) has been developed and characterized. Methods:Two transgenic lines with mutated and inactive human cathepsin D (CatDM1 & CatDM2) have been established. Color fundus photography and fluorescein angiography were performed. For histology transmission electron microscopy (TEM) was used and the retina sections were prepared by conventional methods. Results: Ophthalmological observation showed that at 6 months of age there was no much change detected in fundus photography and fluorescein angiogram in CatDM1 mice. However, peripheral changes were observed in CatDM2 mice at the age of 6 months old. By 12 months of age both transgenic homozygotes have developed hypopigmentation in the periphery of the retina in some mice. Fluorescein angiography revealed hyperfluorescence suggesting retinal atrophy but not leakage. Histological study of the homologous animals at the age of 12 months demonstrated retinal changes, involving abnormal RPE cells and a reduction in the number of photoreceptor cells. The ultra structures of the RPE cells and Bruch’s membrane revealed a major difference between the normal and the transgenic homozygous animals. The most significant changes in the homozygotes were massive deposits in RPE between plasma membrane and basal lamina membrane, basal linear-like deposits in the Bruch’s membrane and large vacuoles in RPE cytoplasm. Conclusions: The in vivo results have demonstrated that the impairment of CatD activation in RPE cells may potentially affect RPE photoreceptor proteolytic function and result in both basal lamina and linear deposits similar to those observed in a patients suffering from aged related macular degeneration.
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