Abstract
Purpose: :
To test the effect of a small peptide inhibitor of the FasR/FasL death receptor pathway on the activation of extrinsic and intrinsicapoptosis pathways in photoreceptors after retinal detachment.
Methods: :
Retinal-RPE separation was created in Brown Norway rats by subretinal injection of 1% hyaluronic acid. In some animals, a small peptide derived from the Fas-binding extracellular domain of c-Met oncoprotein (Met12) was injected into the subretinal space at the time of separation. A mutant peptide or vehicle administered in a similar fashion acted as inactive controls. Caspase 3, Caspase 8, and Caspase 9 activities were measured with a calorimetric assay in retinas harvested at 24 hours after separation. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was performed in retinal sections 3 days after separation.
Results: :
Administration of Met12 into the subretinal space inhibited activation of Caspase 3, Caspase 8 and Caspase 9. In addition, levels of TUNEL-positive staining 3 days after retinal-RPE separation was decreased in animals that received Met12, but not inactive mutant, peptide treatment.
Conclusions: :
A small peptide inhibitor derived from c-Met sequence may serve as a photoreceptor neuroprotectant in the setting of retinal-RPE separation.
Keywords: apoptosis/cell death • photoreceptors • retinal detachment