# Application of an optical defocus model to explore mechanisms underlying myopia and control interventions

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $441,375

## Abstract

Project Summary
Significance: Myopia (short-sightedness) results from a failure of emmetropization in which eyes grow too long
for their optical power. Myopia’s association with sight-threatening complications and projected near-epidemic
levels world-wide (50% by 2050) make it critical that effective treatments for slowing myopia progression be
developed. As an animal model for myopia, the mammalian guinea pig model shares many of the structural
features of the human eyes, including a human-like fibrous sclera. Our proposal takes advantage of our
recently developed contact lens-wearing guinea pig model and related choroidal thickness/vascularity and
retinal pigment epithelium (RPE)-RNA Seq data to explore pharmacological avenues for improved myopia
control under 3 aims: (1) Topical levodopa-carbidoa combination therapy in guinea pig: This combination
of a precursor to dopamine, and an inhibitor of its breakdown will be investigated with respect to its ability to
inhibit defocus-induced myopia, with underlying mechanisms for their anti-myopia actions (retina &/or choroid-
based) explored at the same time. (2) Topical atropine-levodopa-carbidopa combination versus atropine
only therapy in guinea pig; (3) Increased accommodative tone is encoded by RPE & inhibited by
atropine. The goals for aims 2 and 3 are similar to those in (1) of understanding mechanisms. Planned studies
will use advanced ocular imaging and functional testing, as well as routine ocular biometric measurements to
track and compare treatment outcomes. Treatment efficacy will be compared across all 3 treatment arms, in
terms of both interocular differences and changes over time. Comparing data from experiments in Aims 1 and
2 will provide additional insight into their sites of action, with efficacy data for the combination vs. single
ingredient treatments having important translational value. Functional testing also has potential translational
significance, given the recognized role of dopamine in retinal processing, connections with circuits involving
ipRGCs and circadian rhythms and hints of altered visual processing in myopic young adults. Molecular biology
tools applied to timely sampling of RPE from treated and control eyes of the three treatment groups will be
used to obtain additional insight into treatment mechanisms and interactions. Established RPE gene
expression signatures along with choroidal thickness and morphological changes will be used to evaluate
retinal versus choroidal contributions to recorded therapeutic effects (Aims 1 & 2). Aim 3 will provide additional
insight into the mechanism of action of topical atropine.

## Key facts

- **NIH application ID:** 10952028
- **Project number:** 1R21EY036585-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** CHRISTINE FRANCES WILDSOET
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,375
- **Award type:** 1
- **Project period:** 2024-09-30 → 2026-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10952028

## Citation

> US National Institutes of Health, RePORTER application 10952028, Application of an optical defocus model to explore mechanisms underlying myopia and control interventions (1R21EY036585-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10952028. Licensed CC0.

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