# Sex and Gender Supplement to Elastase and Elastin Peptide Activity in Age-Related Macular Degeneration

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $150,263

## Abstract

ABSTRACT
This is an application for an Administrative Supplement for Research on Sex/Gender Influences (NOT-OD-20-
049). The overall goals of the parent R01 (5R01EY030072-02) are to investigate the roles of elastase and
elastin fragments in retina pigment epithelial function (RPE) and health, and how it may be modified in the
presence of the elastase inhibitor, alpha-1 anti-trypsin (A1-AT). The overall hypothesis of the parental grant is
that age- and/or stress-dependent increase in elastase activity leading to elastin degradation and coordinated
production of (anti) α-elastin antibodies are early evens in AMD. As AMD is a disease with greater prevalence
in females, we further hypothesize that elastase activity may vary between sex leading to differences in AMD
development. Therefore, we propose to use increased sample size within an AMD mouse model for retinal
degeneration, as well as additional analysis of a retrospective patient database to measure for differences
between sex. We have developed three specific aims to complement those of the parental grant, allowing for
analysis of biological differences of sex in AMD pathobiology. The first aim will characterize sex differences in
elastin turnover, production of α-elastin antibodies and evidence of ADCC (antibody-dependent cellular
cytotoxicity) and CDC (complement-dependent cytotoxicity) within a mouse model of retinal degeneration. The
second aim will test the hypothesis that α-elastin antibodies in female mice have increased augmented
pathology in a mouse model of RPE damage. For specific aim 3, we will test the hypothesis that A1-AT therapy
results in sex-differences in onset of AMD in human and mouse subjects. Aims 1-3 will utilize experiments
proposed in the parental grant to further explore differences in structure, function, and gene expression
between sex. To analyze sex differences on the onset of AMD in the presence of A1-AT therapy, we will
analyze differences between males and females in the MarketScan Database. This grant supplement will
provide much needed knowledge on how sex may affect differences in AMD pathology. This novel data will aid
in the development of AMD therapeutics and provide information needed to develop a more individualized
approach to health care which considers differences between sex.

## Key facts

- **NIH application ID:** 10334019
- **Project number:** 3R01EY030072-02S1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Baerbel Rohrer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $150,263
- **Award type:** 3
- **Project period:** 2020-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10334019

## Citation

> US National Institutes of Health, RePORTER application 10334019, Sex and Gender Supplement to Elastase and Elastin Peptide Activity in Age-Related Macular Degeneration (3R01EY030072-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10334019. Licensed CC0.

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