# Virally expressed Stanniocalcin-1 for long-term intraocular pressure reduction

> **NIH NIH K08** · MAYO CLINIC ROCHESTER · 2022 · $155,597

## Abstract

ABSTRACT
Glaucomatous optic neuropathy (GON) remains the world’s leading cause of irreversible blindness. At present
time, the only reliable therapeutic target is the reduction of intraocular pressure (IOP), the most prevalent risk
factor for GON, by means of pharmacologic, laser, or surgical intervention. Of these, pharmacologic therapy
with topical eye drop monotherapy is generally the initial treatment of choice for patients with GON. Of the
available medication classes, Prostaglandin F2 analogues (PGF2α) such as latanoprost are often used as first-
line therapy. However, despite its success in reducing IOP in many patients, treatment non-response or side-
effects limit its use in other patients. Furthermore, some studies estimate that less than half of patients use
glaucoma eye drops as prescribed. Additionally, because of the pharmacokinetics and dosing regimens,
fluctuation in IOP is common which also contributes to GON. We recently identified a peptide hormone,
Stanniocalcin-1 (STC-1) that lowers IOP when applied topically and can be expressed in a sustained fashion
with a viral vector to provide sustained IOP reduction. STC-1 was identified in our laboratory’s search of
downstream effector molecules in latanoprost-mediated IOP reduction. To date, we have demonstrated that: 1)
STC-1 is required for the IOP-lowering effects of latanoprost; 2) Topical STC-1 lowers IOP as a stand-alone
drug and is equivalent to latanoprost for IOP reduction in normotensive mice; 3) IOP-lowering effects of STC-1
are independent of the FP receptor; 4) STC-1 lowers IOP in ocular hypertensive mice; 5) STC-1 lowers IOP in
the domestic cat; and 6) STC-1 delivered by adeno-associated virus (AAV-STC-1) lowers IOP in a sustained
fashion in normotensive mice. Our central hypothesis for this application is that expression of STC-1 with a
viral vector will provide an effective, safe, and sustained treatment for IOP reduction that has potential to
benefit the 80 million people worldwide afflicted by glaucoma. Aim 1 will confirm and optimize our
preliminary data that STC-1 can be delivered with a viral vector to provide sustained IOP reduction in
normotensive mice. The data will determine the optimal viral vector for IOP reduction and correlate with tissue
expression, define minimal therapeutic dose of virus, and evaluate safety using histologic methods. Aim 2 will
utilize the optimized viral construct and evaluate IOP reduction in models of ocular hypertension. A steroid-
induced ocular hypertension model as well as the DBA/2J model of pigment dispersion will be used. Additional
measures will include assessment of aqueous outflow parameters. Aim 3 will evaluate viral expression of STC-1
in domestic and primary congenital glaucoma cats as well as to evaluate aqueous humor outflow and safety.
Combined with strong preliminary data and an expert mentorship panel, these aims will support our long-
term goal of developing a novel, targeted, sustained delivery of an IOP-lowering...

## Key facts

- **NIH application ID:** 10462675
- **Project number:** 5K08EY031758-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Gavin W Roddy
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $155,597
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462675

## Citation

> US National Institutes of Health, RePORTER application 10462675, Virally expressed Stanniocalcin-1 for long-term intraocular pressure reduction (5K08EY031758-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10462675. Licensed CC0.

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