Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma.
Document Type
Article
Publication Date
4-2-2012
Keywords
Animals, Axons, Cell Adhesion Molecules, Cranial Irradiation, Disease Models, Animal, Endothelin-2, Gamma Rays, Gene Expression Regulation, Glaucoma, Intraocular Pressure, L-Selectin, Mice, Mice, Inbred DBA, Monocytes, Neurites, Optic Disk, Radiation Chimera, Radiotherapy Dosage, Retinal Ganglion Cells, Transendothelial and Transepithelial Migration, Up-Regulation, Whole-Body Irradiation, X-Rays
JAX Source
J Clin Invest 2012 Apr 2; 122(4):1246-61.
PMID
22426214
Volume
122
Issue
4
First Page
1246
Last Page
1261
ISSN
1558-8238
Abstract
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.
Recommended Citation
Howell G,
Soto I,
Zhu X,
Ryan M,
Macalinao D,
Sousa G,
Caddle L,
MacNicoll K,
Barbay J,
Porciatti V,
Anderson M,
Smith R,
Clark A,
Libby R,
John S.
Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma. J Clin Invest 2012 Apr 2; 122(4):1246-61.