"Assessing a Novel Treatment for Albinism"

EXCITING UPDATE - December 2008. Dr. McKay's group identifies OA1 as the link between melanin synthesis and retinal development in albinism! To read his article, published in the September 2008 PLoS Biology Journal, click here:  http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0060236

 Previous Update: Dr. McKay Research Update - Jan 2008

Principal Investigator: Brian S. McKay, Ph.D., Assistant Professor, University of Arizona

Abstract:

Background: OA1 is a G-protein coupled receptor, a protein family that controls many aspects of tissue development, response, and signaling.  OA1 is only produced by pigmented cells in the eye, hair and skin.  Mutations in OA1 that stop its signaling cause ocular albinism and the full range of retinal developmental deficits.   In the retina, only the retinal pigment epithelium (RPE) is pigmented, and produces OA1.  This means that somehow, pigmentation and OA1 signaling in the RPE control retinal development.  Since OA1 is a signaling protein, our previous work centered on identifying what made OA1 signal, and how that response in the RPE could relate to retinal development.  The basic finding in that work illustrates that OA1 responds to pigmentation, and causes the RPE to secrete neurotrophic factors.  Our view is that loss of OA1 signaling results in a loss of neurotrophic factor production by the RPE, which in turn, changes retinal development.

Aim: To test the activation of this pathway in developing albino animals to determine whether a specific drug (OA signaling protein)can "rescue" the retinal cells, leading to normal retinal development in albino animals.

Method: Pregnant tyrosinase deficient mice will be separated into 2 groups. The experimental group will receive water supplemented with the OA signaling protein, while the control group will receive water that has not been supplemented. OA1 Null mice will also be looked at, as these are a type of mouse which lacks the OA signalling protein receptor. This group will also recieve the supplemented water. After birth, the experimental groups will continue to receive supplemented water, while the control group receives unsupplemented water. On day 14 of life, the mice will  be sacrificed and examined to determine the effect of the signaling protein on development of retinal layers.

Expected Results: Supplementation of tyrosinase deficient mice will lead to an increase in the number of cells in the layers of the retina typically affected in albinism. OA1 Null mice will not improve, as they are lacking the receptor for this signaling protein. The control group would also be expected to not show improvement over baseline.

Learn more about Dr. McKay: Brian_McKay_Research_Interests.mht (489 KB)