The Allen Taylor Lab

Research Publications Cell Biology Pharmacology

 

Age-Related Changes in Vision

The United States will experience a remarkable growth in the older population and it is estimated that 83 million people will be aged 65 and over in 2050. Furthermore, the aging population will confront age-related vision problems with major compromises of quality of life and high health care costs. The Laboratory for Nutrition and Vision Research focuses on understanding aging in the eye to determine the primary causes of age-related debilities in vision and to seek nutritional interventions to delay age-related eye diseases such cataracts and degeneration of the macula (Fig. 1).

Taylor Fig 

Figure 1. Effects of cataracts (left) and age-related macular degeneration (right) on vision

The laboratory pursues its mission principally using clinical/epidemiological studies and laboratory tests in human cohorts, animal models, in cultured human and other mammalian lens or retina tissues, and lens and retina epithelial cells in culture. The major research questions seek to define and understand interrelationships between aging, regulation of lens and retina protein metabolism, protease function and expression and nutrition. This is particularly fascinating because the retina is the fastest metabolizing tissue in the body and the lens is the slowest.

Glycemic Index & Ubiquitin Pathways

High glycemic (typical American) diets deliver sugar rapidly to the bloodstream and to tissues in which glucose is readily incorporated. These include the retina and lens. We found that the consumption of a high-glycemia diet resulted in many AMD features, including retinal pigmented epithelial cell hypopigmentation and atrophy, lipofuscin accumulation (Fig. 2), and photoreceptor degeneration, whereas consumption of the lower-glycemia diet did not. Encouragingly, switching from high to low glycemia diets arrests this damage and this can be translated to a treatment for humans. Currently, there are no such treatments available.

Taylor Fig 1

Figure 2. The autofluorescence puncta indicate greater amounts of lipofuscin in the retinas of high glycemic mice (yellow, right panel). Consuming switching from high to low glycemic diet arrests or reverses this AMD-related damage (compare middle and left panel).

Our proposed schematic of the detrimental effects due to comsumption of high glycemia diets is show in Figure 3. With the intake of the low glycemia diet and when levels of damaged proteins are low, the ubiquitin-proteasome system (UPS) and the lysosomal proteolytic system (autophagy) can degrade the damaged proteins and toxicity is averted (Fig. 3). However, chronic glycative stress (i.e high glycemic index diet) causes enhanced oxidation and glycation-induced protein damage and increased levels of advanced glycation end products (AGES), leading to cellular toxicity. Glycated proteins may include AGES along with unmodified proteins, some including ubiquitin conjugates. These oligomerize and cross-link form toxic higher mass aggregates. The accumulation of these aggregates also sets up vicious cycle of stress, limited proteolytic editing, and further damage to the proteome, resulting in the disease-related accumulation of AGEs and conjugates that is observed in vivo.

A primary biochemical focus of our work is identifying and manipulating degradative pathways (including ubiquitin-dependent processes and autophagic pathways) that are involved in the removal of photooxidized proteins and AGES.

Taylor Fig 3

Figure 3. Schematic representation of how glycation end-products lead to cellular toxicity with HG diets.

Epidemiologic Studies

The Laboratory for Nutrition and Vision Research also conducts epidemiological research focused on ocular diseases research. We collaborate with the Nurses' Health Study at Harvard University, The Age-Related Eye Diseases Study of the National Eye Institute of NIH, The Melbourne Visual Impairment Project (VIP) and The Rotterdam study in the Netherlands.

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The priority application deadlines are as follows:

December 1: Basic Science Division PhD Programs

February 15: Building Diversity in Biomedical Sciences

March 31: Post-Baccalaureate Research Program

May 1: Clinical & Translational Science, MS in Pharmacology & Drug Development

June 15: Online Certificate in Fundamentals of Clinical Care Research