Dejda, A. | bioRxiv Science

bioRxiv2026

Developmental senescence orchestrates hyaloid vessel regression in the postnatal eye

The mammalian eye develops in concert with coordinated growth and remodeling of three vascular networks: the hyaloid vasculature, the choroid and retinal plexus. While retinal and choroidal systems support visual function in the mature eye, the hyaloid network plays a vital yet temporary role supporting the developing lens and inner retina. Regression of the hyaloid network is essential for optical clarity, yet the mechanisms guiding the process remain incompletely understood. Using single-cell RNA sequencing, we show that postnatal mouse hyaloid cells are broadly senescent. Hyaloid vascular smooth muscle, endothelial and immune cells display cell-cycle arrest marked by Cdkn1a with the expression of SASP factors. Genetic ablation of Cdkn1a impedes normal hyaloid regression, demonstrating that developmental senescence is essential for vascular remodeling and functions alongside apoptosis and macrophage-mediated clearance. These findings identify an unrecognized senescence-driven mechanism orchestrating hyaloid involution during ocular development, broadening the understanding of vascular remodeling in the eye.

cell biology↗

bioRxiv2024

Corticosteroids prevent pathological angiogenesis yet compromise reparative vascular remodeling in the retina

Tissue inflammation is often broadly associated with cellular damage, yet sterile inflammation also plays critical roles in beneficial tissue remodeling. In the central nervous system (CNS), this is observed through a predominantly innate immune response in retinal vascular diseases such as age-related macular degeneration, diabetic retinopathy and retinopathy of prematurity. Here we set out to elucidate the dynamics of the immune response during progression and regression of pathological neovascularization in retinopathy. In a mouse model of oxygen-induced retinopathy, we report that broad spectrum corticosteroid drugs such as dexamethasone suppress initial formation of pathological pre-retinal neovascularization in early stages of disease, yet blunt successive waves of reparative inflammation and hence prevent beneficial vascular remodeling. Using genetic depletion of distinct components of the innate immune response, we demonstrate that CX3C chemokine receptor 1 (CX3CR1)-expressing microglia contribute to angiogenesis. Conversely, myeloid cells expressing Lyz-M (lysozyme 2) are recruited to sites of damaged blood vessels and pathological neovascularization where they partake in a reparative process that ultimately restores circulatory homeostasis to the retina. Hence, the Janus-faced properties of anti-inflammatory drugs should be considered when treating retinal vascular disease and particularly in stages associated with persistent neovascularization.

immunology↗