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Abstract #10506 Published in IGR 6-1
Alpha-fodrin is cleaved by caspase-3 in a chronic ocular hypertensive (COH) rat model of glaucoma
Tahzib NG; Ransom NL; Reitsamer HA; McKinnon SJBrain Research Bulletin 2004; 62: 491-495
PURPOSE: α-Fodrin is a neuronal cytoskeletal protein and a known caspase-3 target. The authors sought to determine whether caspase-3 cleaves α-fodrin in COH rat retinas and whether this process is reduced by adeno-associated virus (AAV)-induced retinal ganglion cell expression of baculovirus inhibitory repeat-containing 4 (BIRC4), a potent caspase-3 inhibitor. METHODS: Ocular hypertension was induced unilaterally in five rat eyes by limbal injection of hypertonic saline. In a similar experiment, ocular hypertension was induced in four eyes pre-treated with an intravitreal injection of AAV-BIRC4 to assess α-fodrin cleavage. Western immunoblotting was performed on all retinas. RESULTS: Caspase-3 cleavage of α-fodrin yields a specific 120 kDa protein fragment. COH retina immunoblots indicated significantly more caspase-3 cleavage of α-fodrin than controls (p < 0.01, paired t-test). Inhibition of retinal caspase-3 activity with BIRC4 reduced caspase-3-mediated α-fodrin cleavage compared to controls. CONCLUSIONS: This confirms the authors' previous finding of caspase-3 cleavage of α-fodrin in COH retinas and parallels pathology seen in Alzheimer's disease, in which neurons undergo chronic caspase activation, slow build-up of cleavage products, and delayed apoptosis. If caspase activation in glaucoma leads to protracted rather than rapid retinal ganglion cell apoptosis, a much longer therapeutic window exists for apoptosis inhibition with caspase inhibitors such as BIRC4.
Dr. S.J. McKinnon, Department of Ophthalmology, University of Texas Health Science Center St Antonio, Mail Code 6230, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA
Classification:
3.3 Immunohistochemistry (Part of: 3 Laboratory methods)
5 Experimental glaucoma; animal models
