# Mechanistically linking AMD, glycemic index and protein homeostasis

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 2021 · $366,177

## Abstract

PROJECT SUMMARY
Age Related Macular Degeneration (AMD) is the major cause of blindness. The limited therapies available to
the majority of AMD sufferers demand additional approaches and more pathophysiologic information that can
lead to new drug treatments to prevent or arrest AMD. Encouragingly, recent epidemiologic literature indicates
that consuming lower glycemic index (GI) diets (LG) is related to diminished risk for AMD and AMD
progression in humans. Of concern, consumption of the typical American high GI diet (HG) is quantitatively
associated with higher risk for onset and progress of AMD. Together, the available data indicate that excessive
oxidative and glucose-derived damage (collectively called glycative damage) is associated with and is likely
causative for AMD. Our published and preliminary data suggest that it may be possible to arrest AMD-related
features (AMDf) at an early stage by switching from HG to LG diets. We need masked, randomized clinical
studies to prove the GI-AMD relationship, but these are challenging due to insufficient understanding of the
pathophysiology of the association, high cost, lack of biomarkers, and long duration required. We will address
these voids while also attempting to enhance cellular preservation capacities as a new way to avoid AMDf. In
Aim 1, using wildtype mice consuming HG diets to model the excessive glycative damage associated with
AMD, we will seek to demonstrate that AMDf is delayed or arrested and visual function is prolonged by moving
to lower GI diets. In order to mitigate damage caused by excessive glycative stress, we will also overexpress
the glyoxalase gene GLO1 (a major enzyme that detoxifies glycative damage) and test whether it prevents
AMDf. In Aim 2, we will use advanced mouse and human (comparative) metabolomic data to identify potential
biomarkers of AMDf and reveal pathways and mechanisms of dietary GI-related AMD. These biomarkers will
serve as biomarkers, allowing for “earlier warning” about the need dietary change or therapy. In Aim 3, we will
determine how endogenous protective capacities can be exploited in new ways to preserve retinal function. We
will use two FDA-approved drugs, acarbose and empagliflozin to diminish glycative stress associated with HG
diets. We will also enhance the ubiquitin-proteasome and autophagic degradation systems in order to mitigate
accumulation of damaged and glycated cytotoxic proteins or their precursors, thereby diminishing risk for
AMDf. Together, this research will contribute to improved understanding of- and therapy for- AMD by
elucidating the pathobiology of the dietary GI-AMD relationship. By accomplishing these objectives, we will
help achieve the NEI retina research program's goal to “understand the molecular and biochemical bases for
different forms of AMD, improve early diagnosis, characterize environmental effects on its etiology, and
develop new treatments.” Moreover, since CVD and diabetes are also related to the higher dietar...

## Key facts

- **NIH application ID:** 9989122
- **Project number:** 5R01EY028559-03
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** ALLEN TAYLOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $366,177
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989122

## Citation

> US National Institutes of Health, RePORTER application 9989122, Mechanistically linking AMD, glycemic index and protein homeostasis (5R01EY028559-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9989122. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*