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Scientists Discover Retina Protein That May Help Conquer Blindness

Findings reveal molecular mechanisms leading to visual degeneration

Researchers at Louisiana State University have discovered a protein in the retina that is crucial for vision. In a paper published in Nature Communications, they describe, for the first time, the key molecular mechanisms leading to visual degeneration and blindness.

The authors say that their research has revealed events that may be harnessed for prevention as well as to slow the progression of retinal degenerative diseases.

According to the article, there is growing evidence of the significance of docosahexaenoic acid (DHA), a member of the omega-3 essential fatty acid family, in photoreceptor function and in retinal degenerative diseases, but not much understanding about what governs it. The researchers found that the protein receptor for adiponectin, a hormone that promotes insulin sensitivity and is involved in the metabolic syndrome, has a previously unrecognized function: it also regulates DHA retention and conservation in cells in the eye and is necessary for the function of photoreceptor cells.

“This is the first time that such an integral membrane protein has been localized in the photoreceptor cells and shown to have the capacity to support sight,” said corresponding author Nicolas Bazan, MD, PhD.

DHA, found in fish oil, is vital for proper brain function. It is also necessary for the development of the nervous system, including vision.

Working with a genetic mouse model in which the adiponectin receptor gene was deleted, the researchers found that total and free retinal DHA were diminished in the gene-deficient mice. When they incubated normal retinas with labeled DHA, they measured abundant levels of it, demonstrating that a functional AdipoR1 gene must be present for DHA uptake and retention. In addition, when cultured human retinal pigment epithelial (RPE) cells were incubated with labeled DHA, the DHA within the medium decreased with time while increasing within the cells. Further, when the AdipoR1 gene activity was ramped up in these cultured RPE cells, much more labeled DHA was taken up and incorporated. But when silenced, labeled DHA was diminished, indicating that human RPE cells can also take up DHA and that the AdipoR1 gene plays a significant role in this activity as well.

DHA in brain and retinal cells also builds reservoirs for molecules called into action when normal functions are disrupted, resulting in such conditions as retinal degeneration, Parkinson’s disease, or Alzheimer’s disease. Bazan and his colleagues previously discovered neuroprotectin D1 (NPD1), one such molecule made from DHA when cell survival is compromised. The loss or diminution of retinal DHA leads to visual impairment and may play an important role in the development of blindness from retinitis pigmentosa and other retinal degenerative diseases as well as age-related macular degeneration (AMD), the foremost cause of blindness in people over 50 years of age, the authors said.

“Our model and newly discovered molecular mechanism allow therapies to be tested more rapidly,” Bazan remarked. “We feel an urgency to address blindness and cognition impairments of dementias because of their heavy burden on patients, families, care givers, and the health care system.”

Sources: EurekAlert; March 4, 2015; and Nature Communications; March 4, 2015.

 

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