# The role of STEAP4 in retinal pathogenesis and diabetic retinopathy

> **NIH VA I01** · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · 2024 · —

## Abstract

Twenty-five percent of the Veterans receiving care from the VA are being treated for diabetes. Consequently,
more than half suffer from diabetic retinopathy, which is an incurable disease that can lead to vision loss. The
current treatments for diabetic retinopathy are futile to approximately 75% of diabetics with varying stages of
this blinding disease. Accordingly, new therapeutics are needed. Our proposed studies ultimately relate to this
clinically relevant need. Recently, we discovered STEAP4 (Six-Transmembrane Epithelial Antigen of the
Prostate 4) is upregulated in our VA patients that suffer from diabetic retinopathy. This discovery is noteworthy
because STEAP4 is a metabolic enzyme that can mediate inflammation, oxidative stress, and iron
accumulation, which are intrinsic pathologies of the onset of diabetic retinopathy. Although the function of
STEAP4 in the retina is unknown, our preliminary data provides strong evidence that STEAP4 plays a role in
iron uptake and ROS production in the diabetic retina. We will further investigate the mechanistic details of
STEAP4’s impact on these pathologies. Since ROS and iron accumulation are inherent to the development of
diabetic retinopathy, we will also examine the effect STEAP4 has on ferroptosis, neuroretina damage, visual
function, and vascular impairment. These proposed studies will provide a full understanding of the functional
impact STEAP4 has on the onset and progression of non-proliferative diabetic retinopathy. Subsequently, we
will also examine the intrinsic pathologies of proliferative diabetic retinopathy. Cancer studies provide strong
evidence that IL-17A mediates STEAP4 to induce vascularization. We previously determined that IL-17A
induces retinal neovascularization, and postulate that STEAP4 is the mediated effector of this vascular
proliferation in the retina. To further evaluate this hypothesis, we will examine the unprecedented role of
STEAP4 in retinal neovascularization. Our findings could identify a deduced mechanism of vision loss in
proliferative diabetic retinopathy. Overall, we are optimistic that all of our proposed work will improve our
understanding of this retinal microvascular disease, while identifying a new drug target for diabetic retinopathy.

## Key facts

- **NIH application ID:** 10923555
- **Project number:** 1I01BX006424-01A1
- **Recipient organization:** LOUIS STOKES CLEVELAND VA MEDICAL CENTER
- **Principal Investigator:** Patricia R Taylor
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10923555

## Citation

> US National Institutes of Health, RePORTER application 10923555, The role of STEAP4 in retinal pathogenesis and diabetic retinopathy (1I01BX006424-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10923555. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*