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Abstract #22790 Published in IGR 11-1
α2-macroglobulin is a mediator of retinal ganglion cell death in glaucoma
Shi Z; Rudzinski M; Meerovitch K; Lebrun-Julien F; Birman E; Di Polo A; Saragovi HUJournal of Biological Chemistry 2008; 283: 29156-29165
Glaucoma is defined as a chronic and progressive optic nerve neuropathy, characterized by apoptosis of retinal ganglion cells (RGC) that leads to irreversible blindness. Ocular hypertension is a major risk factor, but in glaucoma RGC death can persist after ocular hypertension is normalized. To understand the mechanism underlying chronic RGC death we identified and characterized a gene product, α2-macroglobulin (α2M), whose expression is up-regulated early in ocular hypertension and remains up-regulated long after ocular hypertension is normalized. In ocular hypertension retinal glia up-regulate α2M, which binds to low-density lipoprotein receptor-related protein-1 receptors in RGCs, and is neurotoxic in a paracrine fashion. Neutralization of α2M delayed RGC loss during ocular hypertension; whereas delivery of α2M to normal eyes caused progressive apoptosis of RGC mimicking glaucoma without ocular hypertension. This work adds to our understanding of the pathology and molecular mechanisms of glaucoma, and illustrates emerging paradigms for studying chronic neurodegeneration in glaucoma and perhaps other disorders.
Dr. H.U. Saragovi, 3755 Cote St. Catherine, E-535, Montreal, QC H3T 1E2, Canada. uri.saragovi@mcgill.ca
Classification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)