Progressive Retinal Vascular and Neuronal Degeneration in BXD32 Mice: A Model for Age-Dependent Neurovascular Pathology

TL;DR

BXD32 mice show progressive retinal vascular and neuronal degeneration with aging, making them a useful model for studying inherited retinal diseases.

Contribution

BXD32 mice are identified as a novel spontaneous model for age-dependent retinal neurovascular degeneration.

Findings

BXD32 mice exhibit progressive vascular dysfunction starting in the deep capillary plexus and spreading to other retinal layers.

Neuronal degeneration, including photoreceptor loss and ganglion cell thinning, accompanies vascular changes in BXD32 mice.

BXD32 represents a genetically tractable model for inherited retinal neurovascular degeneration.

Abstract

Retinal vasculature is essential for maintaining visual function by supporting metabolically active neurons. However, the retina lacks redundant blood supply, rendering it highly susceptible to vascular dysfunction. Understanding mechanisms of retinal vascular abnormalities is critical for therapies that preserve vascular and neuronal integrity, yet progress has been hindered by limited models and genetic diversity. To address this gap, we examined the retinal vasculature in multiple aged strains from the BXD recombinant inbred mouse panel, a genetically diverse, tractable, and physiologically relevant platform for uncovering novel genetic drivers and disease mechanisms. We identified BXD32 as a striking outlier with dramatically reduced vessel density. Using optical coherence tomography, optical coherence tomography angiography, and histological analyses, we comprehensively characterized retinal vasculature and structural integrity of BXD32 mice during aging. We found progressive, age-dependent vascular dysfunction and degeneration, beginning in the deep capillary plexus and advancing to the intermediate and superficial layers. These changes were accompanied by neuronal degeneration, including photoreceptor loss and thinning of the ganglion cell complex. Our findings establish BXD32 as a spontaneous and genetically tractable model of inherited retinal neurovascular degeneration and provide a foundation for future studies to identify causative genetic loci and underlying molecular mechanisms.

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