DHA and Cell Survival

A paper E-published in March, 2006 reports on the role that the omega-3 fatty acid docosahexaenoic acid (DHA) in fish oil plays in protecting cells in the retina from degenerative diseases like age-related macular degeneration and retinitis pigmentosa (1).

In both of these blinding eye diseases, photoreceptors (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 cells (RPE) and the amount of DHA they contain.

The main role of RPE cells is photoreceptor maintenance. RPE cells conduct the daily shedding, internalization and degradation of the tips of photo-receptor outer segments. Now it appears that RPE cells are also crucial to the survival of photoreceptor cells.

Closer to Solving a Complex Riddle

Both RPE and photoreceptor cells are exposed to potentially damaging factors such as sunlight and high oxygen tension on a daily basis. It's known that antioxidants such as lutein afford some protection, but exactly how these cells avoid harm from these and other factors, has been somewhat of a mystery up to now. However, Nicolas Bazan, MD, PhD, Director of the Neuroscience Center of Excellence at LSU Health Sciences Center in New Orleans, working in col-
laboration with Harvard researchers, has made several important discoveries that are beginning to provide answers to this complex question.

One of the answers is the importance of DHA. RPE cells cope with UV and oxidative stress, as well as trauma, by using antioxidants like vitamin E present in cellular membranes. Part of the RPE cells' response to these insults is to activate the synthesis of a major neuroprotective compound called neuroprotectin D1 or NPD1. Oxidative stress and other triggers turn on genes that lead to inflammation and cell death. NPD1 inhibits these genes. RPE cells contain DHA, which has been found to be the precursor to NPD1.

The DHA - NPD1 Connection

RPE cells regulate the uptake, conservation and delivery of DHA to photoreceptor cells. In addition to stimulating the production of NDP1, DHA promotes protective cell signaling by facilitating the expression of helpful rather than destructive proteins. DHA and NPD1 also decrease the production of damaging free radicals.

DHA is known to be in short supply in patients with retinitis pigmentosa and Usher's syndromes, and an oral supply of DHA has been shown to improve the condition of retinitis pigmentosa patients with chronic progressive neurodegeneration (2). Additionally, studies have found that higher dietary intake of DHA is associated with AMD risk reduction. DHA has been shown to promote the survival and inhibit cell death not only of photoreceptor cells, but also of neurons in an experimental model of Alzheimer's disease.

Other important questions remain, including the identification of another receptor believed to be an important pathway for NPD1, and more information is needed about the signals that control NPD1 formation. It's important to define these initial events, notes Dr. Bazan, since early clinical manifestations of retinal degeneration precedes massive photoreceptor cell death.

References

1. Bazan NG. Review. Cell survival matters: docosahexaenoic acid signaling neuroprotection and photoreceptors. Trends in Nueroscience. [Epub ahead of print], March 30, 2006.
2. Berson EI, et al. Further evaluation of DHA in patients with retinitis pigmentosa receiving vitamin A treatment subgroup analyses. Arch Ophthalmol 122:457-64, 2004.