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Abstract #49223 Published in IGR 14-1
Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma
Howell GR; Soto I; Zhu X; Ryan M; MacAlinao DG; Sousa GL; Caddle LB; Macnicoll KH; Barbay JM; Porciatti V; Anderson MG; Smith RS; Clark AF; Libby RT; John SWJournal of Clinical Investigation 2012; 122: 1246-1261
Glaucoma is a common ocular disorder that is a leading cause of blindness worldwide. It is characterized by the dysfunction and loss of retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for the earliest detectable damage to RGCs and their axons in the optic nerve. Here, we show that the leukocyte transendothelial migration pathway is activated in the optic nerve head at the earliest stages of disease in an inherited mouse model of glaucoma. This resulted in proinflammatory monocytes entering the optic nerve prior to detectable neuronal damage. A 1-time x-ray treatment prevented monocyte entry and subsequent glaucomatous damage. A single x-ray treatment of an individual eye in young mice provided that eye with long-term protection from glaucoma but had no effect on the contralateral eye. Localized radiation treatment prevented detectable neuronal damage and dysfunction in treated eyes, despite the continued presence of other glaucomatous stresses and signaling pathways. Injection of endothelin-2, a damaging mediator produced by the monocytes, into irradiated eyes, combined with the other glaucomatous stresses, restored neural damage with a topography characteristic of glaucoma. Together, these data support a model of glaucomatous damage involving monocyte entry into the optic nerve.
Full article
Classification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.15 Optic nerve (Part of: 2 Anatomical structures in glaucoma)
3.9 Pathophysiology (Part of: 3 Laboratory methods)
