Anomalous angiogenesis in retina

TL;DR

This paper presents a computational model of retinal angiogenesis in AMD, suggesting that therapies targeting VEGF, Jagged, and cellular adhesion could improve treatment outcomes.

Contribution

It introduces a novel cellular Potts model simulation of AMD-related angiogenesis, highlighting potential therapeutic targets and strategies.

Findings

Anti-VEGF and anti-Jagged therapies can temporarily halt AMD progression.

Improving RPE and BM cell adhesion may offer longer-term benefits.

Simulations identify key molecular pathways involved in AMD angiogenesis.

Abstract

Age-related macular degeneration (AMD) may cause severe loss of vision or blindness particularly in elderly people. Exudative AMD is characterized by angiogenesis of blood vessels growing from underneath the macula, crossing the blood-retina barrier (that comprise Bruch's membrane, BM, and the retinal pigmentation epithelium RPE), leaking blood and fluid into the retina and knocking off photoreceptors. Here, we simulate a computational model of angiogenesis from the choroid blood vessels via a cellular Potts model, as well as BM, RPE cells, drusen deposits and photoreceptors. Our results indicate that improving AMD may require fixing the impaired lateral adhesion between RPE cells and with BM, as well as diminishing Vessel Endothelial Growth Factor (VEGF) and Jagged proteins that affect the Notch signaling pathway. Our numerical simulations suggest that anti-VEGF and anti-Jagged therapies could temporarily halt exudative AMD while addressing impaired cellular adhesion could be more effective on a longer time span.