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Catalyst For a Cure Research Update
Summary of recent findings published in the peer-reviewed journal IOVS (Investigative Ophthalmology and Visual Science)
Glaucoma is most often associated with elevations in intraocular pressure (IOP), but age also is a significant risk factor.
As we age, the retina and optic nerve naturally undergo a certain amount of functional loss, which is directly linked to a small degree of neuronal degeneration. It is critical in the study of glaucoma to distinguish the degeneration of the retina and optic nerve due to increased IOP from that occurring during normal aging. Catalyst For a Cure (CFC) researchers have done just that in two publications from the March, 2006 issue of Investigative Ophthalmology and Visual Science (IOVS).
In the study by Steele et al.1, the CFC used new microarray technology to compare broad genetic changes in the retina that occur with age-related increases in IOP. The researchers found that one of the most robust changes in gene expression occurs in a family of genes associated with inflammation and known to be involved in diseases of the brain, such as Alzheimer’s disease. As a result of this study, the CFC is pursuing a possible treatment that is known to suppress inflammation in brain disease.
In the study by Inman et al.2, the CFC examined the survival of retinal ganglion cell axons, which comprise the optic nerve, at different ages and IOPs. Their results indicate two important facts that were previously unknown. First, a lengthy period of elevated IOP is not necessary to kill the axons. Even in young optic nerves, elevated IOP is sufficient to induce degeneration. Second, small differences in IOP lead to small differences in axon survival. This indicates that even subtle changes in IOP could affect how the optic nerve functions in glaucoma.
CFC researchers are now working to understand the mechanism that could underlie how small changes in IOP translate to retinal ganglion cell survival in hopes of identifying new therapeutic targets.
- Article by David J. Calkins, PhD and Rebecca M. Sappington, PhD (July, 2006)
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1 Denise M. Inman, Rebecca M. Sappington, Philip J. Horner, and David J. Calkins. Quantitative Correlation of Optic Nerve Pathology with Ocular Pressure and Corneal Thickness in the DBA/2 Mouse Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2006 47: 986-996.
2 Michael R. Steele, Denise M. Inman, David J. Calkins, Philip J. Horner, and Monica L. Vetter. Microarray Analysis of Retinal Gene Expression in the DBA/2J Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2006 47: 977-985.