# Targeting Surfactant Protein A to Prevent Retinopathy of Prematurity

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $482,357

## Abstract

PROJECT SUMMARY
Retinopathy of prematurity (ROP) is a potentially blinding vaso-proliferative disease frequently seen in
prematurely born infants with lifelong consequences for both the infant and society. The c-type lectin,
Surfactant Protein A (SP-A), is an immunomodulatory protein, found to be deficient in prematurely born infants.
Lack of SP-A is associated with lung disease of prematurity and a temporal association with pulmonary
vascular growth factors has been previously reported. We previously discovered that SP-A is expressed in the
Müller retina and plays an important role in neovascular disease (NV) with a pro-angiogenic phenotype. Our
preliminary data now shows SP-A promotes early retinal vascular development, and conversely, lack of SP-A
is seen in response to hyperoxia in rodent models. SP-A has a positive association with expression of retinal
vascular endothelial growth factor (VEGF), cytoskeleton proteins and associated chaperones necessary for
both cytoskeleton and VEGF folding. Our results suggest that deficiency of SP-A leads to reduced vascular
growth in endothelial cells both in the rodent retina and in vitro impacting retinal angiogenesis. Conversely, in
the second stage, SP-A acts in a proangiogenic fashion to drive NV. Given that current anti-VEGF therapies for
ROP may result in delayed re-appearance of NV and may also depress systemic VEGF levels with
consequences for the growing preterm infant, there is a critical need to develop safe and targeted therapies for
ROP and most importantly- to prevent it. We hypothesize that the SP-A protein and associated pathways
represent novel therapeutic targets to rescue early hyperoxia and prematurity related vascular arrest. It is
imperative to understand the mechanisms for these complex cell-intrinsic properties. In this proposal we will
examine cytoskeleton, chaperone and S-A receptor molecules using transgenic strains with targeted deletion
of SP-A and Myo18A receptor in Müller and endothelial cells. We will examine the association between SP-A
and the chaperone aCrystallinB which drive post-translational modification of cytoskeleton and vascular growth
factors. The goals of this proposal are to characterize the SP-A/chaperone/VEGF axis, to confirm Myo18A as
the SP-A receptor and study the impact of SP-A on endothelial cell cytoskeleton and endothelial cell function.
Finally, we will test the therapeutic potential of targeting SP-A protein in early disease in a rodent ROP model.
These goals have clear

## Key facts

- **NIH application ID:** 10980778
- **Project number:** 1R01EY033499-01A1
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Faizah Naheed Bhatti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $482,357
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980778

## Citation

> US National Institutes of Health, RePORTER application 10980778, Targeting Surfactant Protein A to Prevent Retinopathy of Prematurity (1R01EY033499-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10980778. Licensed CC0.

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