# Noninvasive Protection Against Retinopathy of Prematurity

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $442,500

## Abstract

In our ongoing research into the leading ocular cause of childhood blindness, retinopathy of 
prematurity (ROP), we have documented many highly prevalent, clinically significant sequelae that 
persist long after the preterm ages at which ROP is active.  These include short axial length, high 
myopia, anisometropia and, perhaps most critically, persistent retinal dysfunction.  Although these 
outcomes are common, even in eyes in which the ROP was mild (the vast majority), the mechanisms 
that cause and link them remain poorly understood.  We will examine these mechanisms.  Our 
observations in both human ROP subjects and rat models strongly suggest that abnormalities of the 
neural retina, of the vasculature, and of refractive development, are biologically related 
comorbidities, and that retinal neurons, especially rod photoreceptors, instigate the chain of 
events that results in all these sequelae.  Therefore, we will use the oxygen-induced retinopathy 
'ROP rat" model to test our novel hypothesis that persistent neurovascular dysfunction is the basis 
of poor ROP outcomes years after active disease has resolved.  To facilitate ready translation to 
our clinical research and patient care, we will make use of complementary, innovative procedures to 
study the function and structure of the neural retina and its vascular supply, and associations 
with altered refractive development, in individual, living eyes.  Our pioneering approach will 
permit longitudinal study from vaso-obliteration through active ROP to maturity.  This will enable 
individualized developmental growth curves to be derived and quantitative measures of each 
feature (vascular, neural, refractive) to be evaluated for their ability to predict outcomes in 
other features, suggesting cause-and-effect relationships.  In cross-sectional tests at the same 
timepoints, studies of biochemical signaling pathways in subsets of rats will investigate the 
molecular bases of the shared neural, vascular, and refractive patterning mechanisms.  Then, 
mindful that (1) ROP has its onset at preterm ages when the outer segments of the 
energy-demanding rods first appear, (2) the severity of rod dysfunction at a young age predicts vascular 
outcomes but not vice versa, (3) administration of a visual cycle modulator that lowers metabolic 
demands of rods protects the immature retinal neurons and improves vascular outcomes, (4) neural 
and vascular development is under cooperative  molecular  control,  (5) the  retina  is  a  major 
 controller  of  eye  growth  and  refractive  development,  and
(6) photoreceptors use less energy in the light because light suppresses the circulating current, 
we will attempt to beneficially regulate ambient light to the benefit of all these 
sequelae-vascular, neural, and refractive-using a series of dark and light exposures designed with 
reference to the developmental course of the photoreceptors. Light regulation is safe, economical, 
suitable as monotherapy or ...

## Key facts

- **NIH application ID:** 10019555
- **Project number:** 5R01EY028953-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** James Daniel Akula
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $442,500
- **Award type:** 5
- **Project period:** 2019-09-30 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019555

## Citation

> US National Institutes of Health, RePORTER application 10019555, Noninvasive Protection Against Retinopathy of Prematurity (5R01EY028953-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10019555. Licensed CC0.

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