Light induced retinal degeneration activates a caspase-independent pathway involving cathepsin D.
Neuroprotection strategies in the retina aim at interference with regulatory mechanisms of cell death. To successfully target these mechanisms it is necessary to understand the molecular pathways activated in the degenerating retina. Induced retinal degeneration models, like the light damage model, give a synchronized response allowing their detailed investigation. In this study we exposed Fisher rats to a continuous white light. This induced a caspase-independent cell death in which the activation of cathepsin D has an important role via the activation of L-DNase II. Inhibition of this enzyme by intravitreal administration of pepstatin A protects photoreceptors indicating that this enzyme might be an interesting target for neuroprotection.
Chahory
Sabine
S
Ecole Nationale Vétérinaire d'Alfort, URO, 7 Avenue de Général De Gaulle, Paris, France.
Keller
Nicole
N
Martin
Elisabeth
E
Omri
Boubaker
B
Crisanti
Patricia
P
Torriglia
Alicia
A
D000818:Animals; D015153:Blotting, Western; D020169:Caspases / Q000502:physiology*; D002402:Cathepsin D / Q000502:physiology*; D002452:Cell Count; D016923:Cell Death / Q000528:radiation effects; D003851:Deoxyribonucleases / Q000378:metabolism; D004596:Electroretinography; D004789:Enzyme Activation / Q000528:radiation effects; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008027:Light / Q000009:adverse effects*; D008297:Male; D010436:Pepstatins / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000528:radiation effects; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012160:Retina / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects; D012162:Retinal Degeneration / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000528:radiation effects
D010436:Pepstatins; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D003851:Deoxyribonucleases; D010447:Peptide Hydrolases; D020169:Caspases; D002402:Cathepsin D; C031375:pepstatin