# Mechanism of APBB2 contributions to glaucoma

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2021 · $224,797

## Abstract

Abstract
Glaucoma is a group of age-related neurodegenerative diseases characterized by loss of retinal ganglion cells
and their axons. Because RGCs are post-mitotic neurons, their loss is permanent and causes a gradual
decline leading toward irreversible blindness. Unfortunately, glaucoma manifests in a way that damages US
society more broadly—it disproportionately affects certain racial groups. Glaucoma is a worse problem
amongst African Americans than Caucasians. Though socioeconomic factors often contribute to this disparity,
a large part is biological and driven by genomic differences between racial groups. A recent breakthrough
points to APBB2 as central to glaucoma in African Americans. A large genome-wide association study (GWAS)
has found a single nucleotide polymorphism in APBB2 (rs59892895) with genome-wide significance (P=2x10-8;
Odds ratio=1.33), and successfully replicated the finding in additional cohorts. identified a variant in the APBB2
gene as an important cause of glaucoma in people of African descent. ABPP2 encodes a cytoplasmic adaptor
protein with multiple protein-protein interaction domains. Remarkably, the high-risk allele is present in
approximately 21% of African Americans and apparently absent from Caucasians. Our team has contributed to
this discovery of APBB2 as a gene of importance to glaucoma in African Americans, and as additionally shown
in our Preliminary Data, have developed a hypothesis that overexpression of APBB2 is the disease-causing
mechanism. To test this new hypothesis, we recently generated and now have in hand, a mouse model on a
pure C57BL/6J genetic background that is overexpressing Apbb2. The strain was created by the University of
Iowa Genome Editing Facility and features a full-length mouse Apbb2 (transcript variant 1) under control of a
ubiquitous promotor (CAG) and includes a 6His/3XFlag attached to the N-terminus (abbreviated as B6-
Tg(Apbb2). The experiments of this proposal utilize this new strain as a central resource to complete the
important, but somewhat high risk, test via manipulation that over-expression of Apbb2 promotes glaucoma. In
Specific Aim 1, we propose to test the anatomical and physiological consequences over time of Apbb2
overexpression in mice. This Aim will also complete a thorough characterization of the B6-Tg(Apbb2) strain.
Specific Aim 2 will study APBB2 from a molecular perspective, identifying retinal APBB2 binding partners that
will guide future mechanistic and candidate-driven genetic experiments.

## Key facts

- **NIH application ID:** 10248474
- **Project number:** 5R21EY031598-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Michael G Anderson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $224,797
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248474

## Citation

> US National Institutes of Health, RePORTER application 10248474, Mechanism of APBB2 contributions to glaucoma (5R21EY031598-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10248474. Licensed CC0.

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