Correlation Between Autofluorescent Debris Accumulation and the Presence of Partially Processed Forms of Cathepsin D in Cultured Retinal Pigment Epithelial Cells Challenged with Rod Outer Segments

Distribution of Cathepsin D in Human Eyes with or without Age-related Maculopathy

“…The presence of inactive forms of CatD in RPE cells was independent of age but was an intrinsic property of the donor RPE cells. In addition, the presence of inactive forms of the enzyme were linked to an increase in OS derived debris accumulation in OS challenged cultured RPE cells (Rakoczy et al, 1996) suggesting a correlation between debris accumulation and the presence of inactive forms of CatD in RPE cells.…”

“…A general age-related impairment of CatD activity accompanied by the accumulation of immunoreactive but enzymatically inactive forms of CatD has been demonstrated in several organs of senescent rats (Wiederanders and Oelke, 1984 ;Wilcox, 1988). Subsequently the presence of enzymatically active and inactive forms of CatD in cultured human RPE cells was demonstrated (Rakoczy et al, 1996). The presence of inactive forms of CatD in RPE cells was independent of age but was an intrinsic property of the donor RPE cells.…”

Genetic factors of age-related macular degeneration

“…In old age, the mcd/mcd mice exhibit most features of human AMD such as RPE pigmentary changes, attenuation, hyper-and hypoplasia, proliferation and atrophy of RPE cells, accumulation of basal laminar and linear deposits, and decreased retinal sensitivity. Under the light microscope, geographic atrophy appears in the advanced stage (Rakoczy et al, 1996(Rakoczy et al, ,2002.…”

“…Improper cleavage, however, does render circulating CatD enzymatically inactive. These inactive forms are thought to impair rod outer-segment degradation, which eventually leads to the development and accumulation of hyalinized drusen (Rakoczy et al, 1996(Rakoczy et al, ,1999. In old age, the mcd/mcd mice exhibit most features of human AMD such as RPE pigmentary changes, attenuation, hyper-and hypoplasia, proliferation and atrophy of RPE cells, accumulation of basal laminar and linear deposits, and decreased retinal sensitivity.…”

Progressive Age-Related Changes Similar to Age-Related Macular Degeneration in a Transgenic Mouse Model

“…Inactive proCatD accumulation seems to be an abnormal condition and has been associated with breast and ovarian cancers, 2324 and an agerelated increase in the amount of proCatD has been demonstrated in several organs. [25][26][27] Recently, we demonstrated in vitro and in vivo that presence of proCatD impairs POS proteolysis, resulting in POS-derived breakdown product accumulation in the RPE cells of heterozygous transgenic mice (mcd) that express a form of CatD lacking the Glu 44p and Gly 1 cleavage site. 28 We hypothesize that any change, genetic or environmental, that might lead to an accelerated POS breakdown product accumulation in the RPE layer will compromise RPE cell function, initiating changes similar to those observed in AMD.…”