Implication de la voie de la LEI/L-DNase II dans un modèle de dégénérescence rétinienne induite par la lumière

Abstract

Retinal degenerations, a major cause of visual loss in people over 50 years old in industrialized countries, are characterized by the death of photoreceptors. Although they have various origins (genetic, oxidative), these diseases share a common physiopathological mechanism, i. e. death by apoptosis of the photoreceptors. Apoptosis is a programmed cell death mechanism, which results in the destruction of nuclear DNA. Two molecular pathways of apoptosis are known to date : the caspase-dependent pathway, involved in numerous apoptosis models, and caspase-independent pathways, which activate proteases other than caspases. Caspases are intracellular cysteine proteases. Our study focuses on a caspase-independent pathway : the LEI (Leukocyte Elastase Inhibitor)/ LDNase II pathway in a light-induced retinal degeneration model, a model of apoptosis which does not involve the activation of caspases. When subjected to certain apoptosis-inducing factors, LEI, a cytoplasmic protein with anti-protease activity, undergoes post-translational modification and nuclear translocation, producing L-DNase II, a nuclear protein with endonuclease activity. Evidence of the involvement of the LEI/ L-DNase II pathway in this model of retinal degeneration was provided by immunohistochemistry studies and immunoblot analyses, correlated to the endonuclease activity of rat retinal extracts exposed to continuous illumination. Further studies are currently under way, to determine the importance of this pathway in photoreceptor death, and to identify partner proteins able to activate LEI into L-DNase II in this model of apoptosis.