Death inducing ligands are critical for the selective vulnerability of the inner retina to transient global ischemia.
We have previously demonstrated that the delayed cell death that occurs in the inner retina following transient global ischemia is in part apoptotic.In non-neuronal cells, death-inducing ligands(DILs) such as TNF-α and FasL are important in the induction of apoptosis.The purpose of this study was to investigate the role of DILs in the selective vulnerability of the inner retina to ischemic injury. Four groups of mice were subjected to transient global retinal ischemia (high intraocular pressure model) for a period of 45 minutes : wild type, TNFR(p55)-knock out, TNFR(p75)-knock out and lpr(loss of function of Fas receptor). The degree of retinal damage was assessed by measuring the thicknesses of the inner retinal layers. Additionally, electrophysiology (ERG) was performed following ischemia to assess functional outcome. There were TUNEL positive cells within the vulnerable inner retina seen maximally at 24 hours following ischemia. At 7 days subsequent to ischemia,in all groups of mice there was marked thinning of the inner retinal layers with morphological characterstics of apoptosis. ERG at 7 days demonstrated diminished amplitude of the ERG-b wave.In all three groups of mutant mice, there was significantly less morphological damage(mean inner retinal thickness) as well as significant preservation of the ERG-b wave as compared to the wild type animals.The lpr animals demonstrated the greatest protection.These data suggest that DILs play a critical role in the selective vulnerability of the inner retina to transient global ischemia and offer new strategies for the treatment of ischemic neuronal injury.