# Imaging of Retinal Hydroxyapatite as an Early Screen for AMD

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $436,455

## Abstract

Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly in developed
countries, affecting over ten million Americans. The disease onset is gradual, with few symptoms and most
patients unaware until irreversible vision loss is detected by eye examination. It is accepted that the buildup of
deposits of fats and protein in the retina, the best known of which are called drusen, causes the death of the
light-sensitive cells there. While the less common, “wet” form of AMD (CNV) can be arrested by drugs called
VEGF inhibitors, the more common, “dry” form (GA) is currently untreatable, although several treatments are in
development. Recently, we discovered that drusen contain microscopic spherules of hydroxyapatite (HAP), a
form of calcium phosphate abundant in bones and teeth, and developed evidence indicating that the spherules
nucleate the growth of drusen in the retina. We found that fluorescent stains developed to study bone growth
would also stain the spherules, permitting them to be studied by fluorescence imaging of the retina. We
inferred that detecting the HAP spherules early by such an imaging approach used in vivo might predict the
appearance of the drusen and thus AMD development; this was confirmed in at least some cases.
Thus, the thrust of this Bioengineering Research Grant is to develop and validate a retinal imaging approach
for screening and early detection of AMD, both to cue treatment, and to follow the course of the disease to
assess treatment. Some of the stains synthesized for bone studies in animal models perform well in vitro, but
their behavior and safety is little known in animals, and there are no human studies at all. However, some
tetracycline antibiotics also give bright fluorescence when bound to bone mineral, and we found that they have
a distinct fluorescence lifetime under these conditions, which can be resolved from the background
fluorescence of the retina by fluorescence lifetime imaging. The tetracyclines have well known behavior, can
probably be administered orally, and are very safe in humans. To image the spherules with tetracycline
staining we must construct a fluorescence lifetime imaging ophthalmoscope (FLIO), usable on humans or the
only good animal model for AMD, macaques (monkeys). We will construct a FLIO based on an existing
instrument, refine our procedures on donor cadavers, then test the FLIO and staining procedures on aged
macaques (which develop spherules) and a Japanese macaque which develops drusen early and rapidly as a
result of a high fat diet. Key questions to be answered are how reliably the appearance of spherules predicts
the development of drusen and progression to AMD, and how safe the imaging procedure is for the monkeys;
satisfactory results will likely lead to trials in humans.

## Key facts

- **NIH application ID:** 10176510
- **Project number:** 5R01EY030443-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** RICHARD Blair THOMPSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $436,455
- **Award type:** 5
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176510

## Citation

> US National Institutes of Health, RePORTER application 10176510, Imaging of Retinal Hydroxyapatite as an Early Screen for AMD (5R01EY030443-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176510. Licensed CC0.

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