“The content of US Ophthalmic Review is excellent. I am particularly pleased to see sections related to ocular melanoma.”
By Janet Manson
Glaucoma is a leading cause of blindness, characterized by the loss of retinal ganglion cells (RGCs) and their axons. The initial processes that are necessary for RGC injury are currently unknown however treatments for this condition target pressure elevation within the eye and in many cases are ineffective. A better understanding of the aetiology of the disease is needed to design more successful treatment strategies.
Two studies published in the last decade have hinted that γ-radiation may have a protective effect against the development of glaucoma. In a study published in 2005 it was found that a single dose of whole body irradiation, along with bone marrow transfer in DBA/2J mice (a widely used animal model of glaucoma) was protective against glaucoma development 1. No mechanism for this result was reported, however 96% of treated mice eyes were glaucoma-free one year post-treatment. In a second paper, published in 2004, it was noted that Japanese atomic bomb blast survivors have a very low incidence of glaucoma 2. In this epidemiological study of 10,000 Japanese survivors higher radiation exposure was associated with lower incidence of glaucoma 2.
Following the results of their earlier work 1, a recent study by Jackson Laboratory researchers has reported that administration of a therapeutically relevant x-ray treatment to a single eye is as protective against glaucoma as whole body γ-radiation 3. Mice eyes that were exposed to 3.6 Gy or greater of γ-irradiation were robustly protected from glaucoma. Using genome expression data of optic nerve head tissue, researchers found that radiation treatment alters activation of the leukocyte transendothelial migration pathway offering a key insight into the early stages of disease development. Additionally it was demonstrated that entry of monocytes into the eye occurs early in DBA/2J glaucoma, prior to ocular damage. Treatment with γ-irradiation was found to change the activation of endothelial cells in response to proinflammatory signalling, and prevent monocytes migrating into the eye. Finally, experiments were performed that showed monocytes express damaging molecules that appear critical for nerve damage in glaucoma. The key findings from this research are the importance of monocyte migration in the development of glaucoma, and more significantly, that x-ray treatment has the potential to prevent these processes. Although further work is necessary to determine how x-ray treatment is protective over such an extended time period, this study offers key insights into the early processes involved in the development of glaucoma, as well as offering potential new therapeutic targets for the future treatment of glaucoma.
1. Anderson MG, Libby RT, Gould DB, et al., High-dose radiation with bone marrow transfer prevents neurodegeneration in an inherited glaucoma, Proc Natl Acad Sci U S A, 2005;102:4566-71.
2. Yamada M, Wong FL, Fujiwara S, et al., Noncancer disease incidence in atomic bomb survivors, 1958-1998, Radiat Res, 2004;161:622-32.
3. Howell GR, Soto I, Zhu X, et al., Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma, J Clin Invest, 2012; http://www.jci.org/articles/view/61135