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S. Chahory, L. Padron, C. Daniel, N. Keller, A. Torriglia; Involvement of the LEI/L–DNase II Pathway in Light–Induced Retinal Degeneration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2045.
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Despite various origins, retinal degenerations are characterized by the apoptotic death of photoreceptors. Apoptosis is an active cell death mechanism, in which the cell activates proteases and endonucleases that will dismantle cellular structure. Two main pathways of apoptosis are presently described : the caspase–dependent pathway, which triggers activation of caspases, and the caspase–independent pathways, which activate other non caspases proteases Our study investigates the activation of the LEI (Leukocyte Elastase Inhibitor)/L–DNase II in a light–induced retinal degeneration model in which caspases are not activated. LEI/L–DNase II has been involved in numerous caspase–independent models of apoptosis. In its native form, LEI, a cytoplasmic protein, has an anti–protease activity. Under some apoptotic conditions, LEI is cleaved and becomes L–DNase II, which migrates to the nucleus and acquires an endonuclease activity.
Eight weeks–old Fischer rats were exposed to a constant white light for one to nine days to induce retinal degeneration. Western blot analysis, indirect immunofluorescence and endonuclease activity measurements were used to determine the L–DNase II activation. Molecular biology and enzymological methods were used to characterize the proteases that may be able to activate LEI into L–DNase II. The morphology of this light–induced retinal degeneration was studied by Electron Microscopic Analysis.
Immunohistochemistry shows a nuclear translocation of L–DNase II confirmed by an increase of L–DNase II seen by immunoblot in the purified nuclei of these retinas. This also was confirmed by L–DNase II activity measurements. The measure of several proteases activity showed an increase of the activity of Cathepsin D, a serine protease that is able to activate the LEI into L–DNase II. The activity of Calpains, that has been already shown to be involved in similar model, also increased.
The present study indicates that the LEI/L–DNase II is activated during photoreceptor cell death in light–induced retinal degeneration, an activation that could be mediated by Cathepsin D.
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