# Imaging of Hydroxyapatite as an Early Screen for Age-Related Macular Degeneration

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $352,468

## Abstract

Summary/Abstract
To date numerous investigators have noted similarities between many features of Age-Related
Macular Degeneration (AMD) and Alzheimer Disease (AD), suggesting that they share etiologic
and mechanistic attributes, and that it might thus be fruitful to adapt diagnostic and/or treatment
approaches for one to the other (reviewed in(Ohno-Matsui 2011, Ashok, Singh et al. 2020)). In
particular, AMD and AD share certain risk factors such as aging, inflammation, smoking,
dyslipidemia, and the presence of deposits containing specific proteins including amyloid-beta,
but few genetic risk factors.
We discovered (Thompson, Reffatto et al. 2015) that sub-retinal pigment epithelial (sub-RPE)
deposits of many types described as drusen contain microscopic spherules of hydroxyapatite
(HAP; Ca5(PO4)3OH, found in bone mineral) and proposed that this mineral might nucleate the
growth of drusen in the retina and promote the development of AMD. Since then, our
collaborators have found that a subset of larger HAP deposits (“nodules”) is significantly
associated with progression to advanced AMD within one year (odds ratio: 6.4, p = 0.001; (Tan,
Pilgrim et al. 2018)). The focus of our current NEI R01 is a study of whether retinal HAP
deposition presages the rate and extent of drusen formation in a non-human primate model of
AMD. The study images retinal HAP in vivo in a monkey model of AMD with a novel technique:
fluorescence lifetime imaging ophthalmoscopy (FLIO) using a legacy oral antibiotic as a specific
stain for HAP. We have shown that aged retinas can be stained with chlortetracycline infused
from the bloodstream ex vivo, and that stained drusen can be imaged by fluorescence lifetime
imaging (Szmacinski, Hegde et al. 2020). Our collaborators and others have recently observed
that AD patients exhibit peripheral drusen with HAP (e.g., (Csincsik, MacGillivray et al. 2018) ,
as well as phospho-tau-calcification in the brain, and these drusen are evidently useful for
classification of AD patients in the clinic (Csincsik, Quinn et al. 2021) suggesting that widefield
fluorescence imaging of calcification in the peripheral retina might be predictive of AD.
With the supplement, we propose a pilot study to assess our imaging method's capability to
detect peripheral HAP-containing drusen, and the correlation between them and gold standard
markers of AD: deposition of beta-amyloid and phospho-tau in the brains of human donors. We
have ready access to a sizable donor cohort on campus at low cost that will permit a pilot study
during the term of the supplement. In addition, we will genotype the donors for the main AMD
and AD risk SNPs to see if number, size, and/or radial distribution of peripheral drusen are
correlated with AD risk factors. Finally, we plan to test whether we can use two photon
excitation to image the stained drusen in the cadaver retina, which we believe will provide better
accuracy and precision with improved safety.

## Key facts

- **NIH application ID:** 10499173
- **Project number:** 3R01EY030443-03S1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** RICHARD Blair THOMPSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $352,468
- **Award type:** 3
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499173

## Citation

> US National Institutes of Health, RePORTER application 10499173, Imaging of Hydroxyapatite as an Early Screen for Age-Related Macular Degeneration (3R01EY030443-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499173. Licensed CC0.

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