# Regulation of Scleral Growth and Remodeling in Myopia

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $355,500

## Abstract

Myopia is a significant global public health concern. Despite continued research on the regulation of eye size
and refraction, no therapeutic targets have been identified and no pharmaceutical or optometric approaches
have proven effective in the majority of cases. The increasing prevalence of myopia and earlier age of onset
emphasize the need for the identification of pharmaceutical targets for the development of an effective therapy.
Therefore, the long-term goal is to identify the effector molecules that mediate scleral remodeling as they may
facilitate the design of therapies to slow or prevent the progression of myopia. Evidence is accumulating to
suggest that all-trans-retinoic acid (atRA) is an important molecular signal for the control of postnatal ocular
growth. Our recent work indicates that atRA is regulated by choroidal expression of retinaldehyde
dehydrogenase 2 (RALDH2) and transported to the sclera by the HDL-associated protein, apolipoprotein A-1
(ApoA-1). The identity of the choroidal cell type(s) responsible for RALDH2 and ApoA-1 synthesis is currently
unknown. Furthermore the role of ApoA-1 in the regulation of atRA activity and transport in the eye remains to
be elucidated. Most importantly, a direct connection between choroidal atRA, scleral remodeling and eye growth
in vivo has yet to be established. Therefore, the objective of the current proposal is to define the key events
that regulate choroidal atRA synthesis, transport and activity in scleral remodeling during visually guided ocular
growth. The central hypothesis of this proposal is that choroidal atRA concentrations, regulated by the activity of
RALDH2, effect changes in scleral ECM remodeling and thereby control the rate of ocular elongation. Based on
this hypothesis, we predict that modulation of choroidal RALDH2 activity will directly affect ocular elongation.
We propose to test our central hypothesis and accomplish the objective of this application by pursuing the
following three specific aims: 1) Identify the atRA synthesizing cells in the choroid; 2) Elucidate the role of
ApoA-1 in retinoid transport for the regulation of ocular growth; and 3) Assess the effects of pharmacologic
inhibition of RALDH activity on eye growth. The work proposed in aims 1 and 2 is anticipated to describe a
previously uncharacterized cell population(s) responsible for atRA synthesis, and will elucidate a new
mechanism of extracellular atRA transport. These results will be applied to the development of new strategies
for in vivo modulation of choroidal atRA synthesis (Aim 3). The approach is innovative, because it takes
advantage of the latest technologies available in imaging, transcriptome analyses and proteomics to define the
“final common pathway” in the retinal-to-scleral chemical cascade that regulates postnatal, visually guided
ocular growth. The proposed research is significant because it will provide a broader understanding of the
regulation of atRA synthesis, transport and act...

## Key facts

- **NIH application ID:** 9987617
- **Project number:** 5R01EY009391-27
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Jody A Summers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $355,500
- **Award type:** 5
- **Project period:** 1992-01-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987617

## Citation

> US National Institutes of Health, RePORTER application 9987617, Regulation of Scleral Growth and Remodeling in Myopia (5R01EY009391-27). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9987617. Licensed CC0.

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