Nicolas Bazan Laboratory

 

A novel key molecular mechanism leading to
visual degeneration and blindness.

 

Basic RPE with good and bad cells 110615

     This research reveals events that may be harnessed for prevention, as well as to slow down progression, of retinal degenerative diseases. The paper is published in Nature Communication (Rice et al., Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival.Nat Commun. 2015 Mar 4;6:6228. http://www.nature.com/ncomms/2015/150304/ncomms7228/full/ncomms7228.html).

     It was found that the protein receptor for adiponectin, a hormone that promotes insulin sensitivity and is involved in the metabolic syndrome, has a heretofore unrecognized function in vision. The receptor the current paper shows also regulates the omega-3 fatty acid family member docosahexaenoic acid (DHA) retention and conservation in cells in the eye and is necessary for photoreceptor cell function. 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. When they deleted the adiponectin receptor gene, retinal DHA were selectively diminished. 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. Additionally, when cultured human retinal pigment epithelial (RPE) cells were incubated with labeled DHA, DHA within the medium decreased with time while increasing within the cells.  Also, 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, too. 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 or Alzheimer’s disease. Dr. Bazan and his colleagues previously discovered neuroprotectin D1 (NPD1), one such molecule made from DHA when cell survival is compromised. Loss of, or diminished, 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 older than 50 years. This new model and newly discovered molecular mechanism will allow therapies to be tested. We feel an urgency to address blindness and cognition impairments because of their heavy burden on patients, families, care givers and the health care system. DHA, found in fish oil, is an essential omega-3 fatty acid and is vital for proper brain and retina function. It is also necessary for the development of the nervous system, including vision.