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

Publication/Presentation Date

1-1-2026

Abstract

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Volume

13

First Page

1745351

Last Page

1745351

ISSN

2296-858X

Disciplines

Medicine and Health Sciences

PubMedID

41810243

Department(s)

Fellows and Residents

Document Type

Article

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