Metabolic Pathways of the Retina in Health and AMD

Yan Chen, PhD
The University of Texas Medical Branch at Galveston (Galveston, TX)

Co-Principal Investigators

Dean Jones, PhD
Emory University (Atlanta, GA)
Year Awarded:
2017
Grant Duration:
July 1, 2017 to June 30, 2019
Disease:
Macular Degeneration
Award Amount:
$160,000
Grant Reference ID:
M2017186
Award Type:
Standard
Award Region:
US Southwestern
Yan Chen, PhD

Metabolic Regulation by Mechanistic Target of Rapamycin in the Retinal Pigment Epithelium

Summary

Every morning when we open our eyes to see the world around us, the neurons in our retina begin to work.  Their intense work load demands high energy.  The retinal neurons rely on their supporting cells, such as retinal pigment epithelium (RPE) cells, to provide them with the fuel to meet their energy needs.  In this project, we will study the mechanisms of energy production and regulation, in both healthy and diseased eyes, particularly those with AMD.

Details

The retinal pigment epithelium (RPE) is a layer of cells next to the retina that are metabolically coupled to the retina’s photoreceptor neurons.  In age-related macular degeneration (AMD), functional interactions between the two types of cells are disturbed, which will result in both defects in energy metabolism and inefficient removal of metabolic intermediates in the outer retina.  Limited information is available for metabolic profiles of eye tissues, and the mechanistic links between RPE metabolomics and retinal degeneration are yet to be determined.

Mechanistic target of rapamycin (mTOR) is a key regulatory protein that controls the balance between cellular anabolism and catabolism.  We recently found that abnormally high activity of mTOR leads to degeneration of the RPE and retina.  The current project will use high-resolution mass spectrometry-based metabolomics approaches to measure temporal and spatial changes of metabolic pathways in the RPE and retina under both physiological and disease conditions, with a focus on mTOR-mediated signal transduction pathways.  The findings from our proposed studies will further define how the RPE supports the photoreceptor functions via metabolic coupling, and hopefully identify novel druggable targets for preventing RPE and retinal degeneration during AMD.

About the Researcher

Dr. Yan Chen received her PhD from Emory University.  She then worked at the Vanderbilt Eye Institute as a postdoc fellow under the supervision of Dr. Paul Sternberg.   Currently, she is an assistant professor in the Ophthalmology and Neuroscience Departments at the University of Texas Medical Branch at Galveston.  Her main research interests lie with investigating key signaling mechanisms in retinal pigment epithelium, with the focus on the pathway mediated by mechanistic target of rapamycin (mTOR), and to identify molecular targets that can potentially be translated into interventional targets for treating chronic ocular diseases such as AMD.  

Personal Story

Eyes are small, but eyes are all for me.  I cannot imagine living a single day without eyesight.  I know this for sure.  When I don’t have eyeglasses, I cannot see, and I cannot even hear clearly. 

Unfortunately, with aging, we have problems here and there that affect the vision.   Some are minor, but some are more serious, like AMD.  AMD is not so far from me; my grandmother had it and in the future it may affect my own vision.  When I think about it, I am glad that I am, in fact, a vision researcher, and am working to understand the underlying mechanisms of AMD and define new strategies to treat the disease.  I am also extremely grateful that there are generous donors like those who support the BrightFocus Foundation, who value good eyesight and vision research.  Your support will help everyone to see a clearer and a prettier world.

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