Medical Student Research Fellowship for Summer 2009

Mentor: Wojciech Kedzierski, Ph.D., D.Sc.
Department: Ophthalmology
Room number: E7. 239
Mail Code: 9057
Phone number: 214-648-9212
E-mail: wojciech.kedzierski@utsouthwestern.edu
Project title: Rescue of retinal lipid deficiency in a mouse model of Stargardt disease-3

Animal subjects IRB approved project number (where applicable): 2007-0171
Project Type: Animal-based research

Brief Description of Project:

Background: Stargardt disease-3 is a juvenile dominant macular dystrophy caused by mutations in elongase of very long chain fatty acids-4 (ELOVL4). Pathogenic mutations cause loss of a peptide signal which targets the enzyme to the endoplasmic reticulum, the site of long chain fatty acid synthesis. Our Stargardt-3 mice, a gene-knockin genetic model of the disease, replicate features of the human pathology and show a selective deficiency of polyunsaturated C28-C36 fatty acids in the retina. Our mouse model, and studies with transgenic ELOVL4 expressed in culture cells, both establish ELOVl4 as the enzyme catalyzing the rate limiting elongation steps for synthesis of C28-C36 fatty acids. ELOVl4 is highly expressed in the retina suggesting local synthesis of the deficient lipids.

Aim: This summer project will test whether supplementation with a polyunsaturated C28 fatty acid can rescue the retinal deficiency of polyunsaturated C28-C36 fatty acids in our mouse model of Stargardt disease-3.

Experimental Design: To test the efficacy of supplementation for retinal lipid rescue, Stargardt-3 mice will be administered a polyunsaturated C28 fatty acid followed by isolation of retinal tissue and lipid analyses. A total of 20 mice will be involved in the project. The student will work with Dr. Anne McMahon, research scientist.

Significance: The long-term goal of our studies is to design potential treatments for Stargardt disease-3, a disease for which at present there is neither a cure nor a scientifically-based prevention strategy. A finding of rescue of C28-C36 fatty acid levels will lend support to design and testing of a C28-C36 fatty acid supplementation strategy as a treatment paradigm for Stargardt-3 patients.

Previous Research Activities or Publications with Medical Students:
None