# Efavirenz treatment improves retinal vaso-obliteration and pathological neovascularization in a mouse model of retinopathy of prematurity

## TL;DR

Efavirenz treatment in mice with a model of retinopathy of prematurity reduces harmful blood vessel growth and improves retinal health.

## Contribution

This study reveals that CYP46A1 activation with efavirenz can alleviate retinal pathologies in a mouse model of retinopathy of prematurity.

## Key findings

- EFV treatment reduced pathological neovascularization and avascular areas in OIR mice retinas.
- EFV limited reactive gliosis and microglia activation while improving retinal ganglion cell survival.
- CYP46A1 and its metabolite 24HC are dysregulated in OIR, and EFV treatment partially reverses this.

## Abstract

Previous studies have shown the metabolic and regulatory significance of CYP46A1 in the adult retina; however, its role in the developing retina is unknown. Here, we evaluate CYP46A1 expression and the impact of its activation in the developing mouse retina under normal and pathological conditions.

Seven-day-old (P7) C57BL/6 J mice maintained in room air (controls) or subjected to oxygen-induced retinopathy (OIR) were treated with/without 20 mg/kg efavirenz (EFV), a CYP46A1 activator administered intraperitoneally from P7 to P17.

Retinal cross sections and flat mounts were prepared to study retinal vasculature morphology, Müller and microglia activation, and ganglion cell viability. EFV treatment significantly reduced pathological neovascularization and the size of avascular and hypoxic areas in OIR mice retinas. EFV treatment additionally limited reactive gliosis and microglia activation and improved retinal ganglion cell survival in OIR mice.

The current study demonstrates the developmental regulation of CYP46A1 and the dysregulated expression and levels of the downstream metabolite 24-Hydroxycholesterol (24HC) in OIR mice. The study further suggests that EFV treatment (in part via CYP46A1 activation) may improve key pathological features associated with pathological neovascularization in OIR mice.