Getting to the Root of Fat Transport Dysfunction in Age-Related Macular Degeneration

Project Summary

Dysfunctional fat or lipid transport has emerged as an important factor in age-related macular degeneration, and fat deposits in the eye are an important feature of the disease. Retinal pigment epithelium is a key tissue that sustains damage in this disease and is responsible for processing and transporting lipids. Catharina Grubaugh, PhD, and her colleagues plan to focus on a protein in the retinal pigment epithelium that drives lipid packaging to clarify its role in maintaining retinal health.

To get at the root of this process, the researchers will compare results using lab models that produce or do not produce the protein, called microsomal triglyceride transfer protein. By knocking out manufacture of this protein only in the eye, Dr. Grubaugh and her colleagues will get an understanding of what happens when it cannot do its proper job. They'll compare these results with eyes that have a functioning form of the protein. Dr. Grubaugh and her colleagues hypothesize that this protein will prove to be critical to retinal health.

To connect these findings directly to age-related macular degeneration, the researchers also plan to test the effects of a high-fat diet in lab models that do not produce the protein, with aging included as a factor. This part of the work will sort out how two risk factors for age-related macular degeneration—a diet high in fat and aging—together with the loss of this lipid-processing protein affect the eye. 

Dr. Grubaugh and her team are the first group to examine these factors in intact living systems, using genetically altered lab models. Their work will address this significant knowledge gap, providing insight into how lipids are normally transported within the eye and how these pathways become dysfunctional in age-related macular degeneration. They expect their results to help identify potential treatments for defective lipid transport in the eye, which may be able to prevent or slow the progress of the disease.