Louisiana State University Health Science Center.
April 6, 2006
n invited paper published in Trends in Neuroscience this week by Nicolas G. Bazan, MD, PhD, Boyd Professor and Director of the Neuroscience Center of Excellence at LSU Health Sciences Center in New Orleans, reports on the role that the omega-3 fatty acids in fish oil play in protecting cells in the retina from degenerative diseases like retinitis pigmentosa and age-related macular degeneration, the leading cause of loss of vision in those older than 65. The paper is titled, Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors.
In these blinding eye diseases, photoreceptor cells (rods and cones) degenerate and die. Although this process can be triggered by many different things, one of the most significant protective factors may be the close association of retinal pigment epithelial (RPE) cells and the amount of docosahexaenoic acid (DHA) in them. The main role of RPE cells is photoreceptor maintenance -- they conduct the daily shedding, internalization, and degradation of the tips of the photoreceptor outer segments. It now appears that RPE cells are also key to the survival of photoreceptor cells.
Both photoreceptor and RPE cell types are normally exposed to potentially damaging factors such as sunlight and high oxygen tension.
How the cells avoid damage from these factors and others has been a mystery, up to now. Dr. Bazan's LSUHSC group, in close collaboration with colleagues at Harvard, has made several key discoveries that are beginning to provide answers to this complex riddle. One of them is the importance of DHA. RPE cells cope with sunlight and oxidative stress, as well as trauma, by using antioxidants like Vitamin E, present in the cells. Part of the RPE cells' response is to activate the synthesis of a major neuroprotective compound, which Dr. Bazan and colleagues discovered, called neuroprotectin D1 (NPD1). NPD1 inhibits genes causing inflammation and cell death that oxidative stress and other triggers turn on. RPE cells contain the omega-3 fatty acid family member, DHA, which Dr. Bazan and colleagues found is a precursor to NPD1. RPE cells regulate the uptake, conservation, and delivery of DHA to the photoreceptor cells. DHA, known to be in short supply in patients with retinitis pigmentosa and Usher's syndrome, promotes protective cell signaling by facilitating the expression of helpful rather than destructive proteins a
s well as stimulating the production of NPD1. DHA and NPD1 also decrease the production of damaging free radicals. DHA has been shown by Dr. Bazan to promote survival and inhibit cell death not only of photoreceptor cells, but also of neurons in an experimental model of Alzheimer's disease.
Questions remain, including the identification of another receptor believed to be an important pathway for NPD1, more information about the signals that control the formation of NPD1, and if NPD1 or a synthetic counterpart might be effective when administered therapeutically.
"Because the early clinical manifestations of most retinal degeneration precedes massive photoreceptor cell death, it is important to define the initial crucial events," notes Dr. Bazan. "This knowledge might be applicable to the design of novel therapeutic interventions to halt or slow disease progression."
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