# Racial Disparities in glaucoma:  Implications of SDPR/Cavin2 in human trabecular meshwork

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $196,875

## Abstract

Project Abstract:
Understanding the pathogenesis of glaucoma, a leading cause of blindness, is an important
goal of vision research. As indicated in numerous population-based studies, individuals of
African descent develop glaucoma at an earlier age with increased severity and risk of
blindness compared to Caucasians (CC). The fundamental mechanisms for these disparities
are unknown, but genetic influences likely contribute to these phenotypic differences. The TM is
important in the regulation of intraocular pressure, the most important and only current
modifiable risk factor for glaucoma development. Differential gene expression analysis by RNA
sequencing (RNAseq) and quantitative polymerase chain reaction (qPCR) compared trabecular
meshwork (TM) specimens from African American (AA) and CC glaucoma patients obtained
during surgery indicated SDPR (also known as Cavin2) had significantly lower expression in AA
patients compared to CC. This finding led to explorations of how it may be related to physiology
and pathology of the TM. SDPR, together with other cavins and caveolin proteins, is associated
with regulation of caveolae, sub-microscopic, plasma membrane pits, which have been noted to
be abundant in TM. Caveolae are linked to a wide range of cellular functions and disease, but
the role of these structures in the eye has not been elucidated. These organelles are composed
of caveolin (CAV) and cavin proteins. Gene variants near the CAV1/CAV2 encoding gene in
genome wide association studies have been identified in glaucoma patients in select
populations. The first specific aim will evaluate expression of SDPR gene/protein as it relates to
the ultrastructural changes of caveolae in TM from both AA and CC glaucoma patients and
healthy cadaver donors, utilizing both standard and immunogold labeling transmission electron
microscopy for SDPR and CAV1. The second specific aim is to investigate SDPR-specific short
hairpin RNA (shRNA)-mediated gene silencing in cultured human TM cells to evaluate
phenotypic correlations in caveolae as identified in our preliminary observations in POAG TM. In
contrast to self-reported racial background, all glaucoma specimens and healthy donor tissues
will be confirmed by DNA genotyping, representing more accurate racial ancestry for data
analysis. This innovative study represents the first exploration of SDPR/Cavin2 gene
expression, protein distribution and ultrastructural effects in human TM and should provide
valuable insights into a novel mechanism underlying racial disparities in POAG. The knowledge
gained in these studies may lead to new therapies for and strategies to prevent/treat this
blinding disease.

## Key facts

- **NIH application ID:** 9993531
- **Project number:** 5R21EY030618-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** CARLA J SIEGFRIED
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,875
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993531

## Citation

> US National Institutes of Health, RePORTER application 9993531, Racial Disparities in glaucoma:  Implications of SDPR/Cavin2 in human trabecular meshwork (5R21EY030618-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9993531. Licensed CC0.

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