Macrophage-Integrated 3D Outer Blood-Retinal Barrier Model to Investigate Subclinical Choroidal Neovascular Age-Related Macular Degeneration

Authors

• C Cargill
• R Quinn
• T Park
• C Zhang
• E Nguyen
• D Bose
• MJ Song
• M Ferrer
• R Sharma
• K Bharti

Abstract

Neovascular age-related macular degeneration (nAMD) is a severe, progressive eye disease marked by the invasion of choroidal capillaries into the sub-retinal pigment epithelium (subclinical type I nAMD) and, in more advanced stages, into the subretinal (type II nAMD) space, leading to significant vision impairment. Current models insufficiently replicate the pathogenesis and mechanism of type I nAMD and its progression to type II nAMD. Interestingly, studies have linked nAMD development to the presence of inflammatory cells from innate immune system, such as macrophages, at the site of vascularization. It is hypothesized that macrophages contribute to nAMD as they are a major source of proinflammatory and proangiogenic factors. In this study, we engineered a 3D bioprinted outer blood-retinal barrier model incorporating a polarized retinal pigment epithelium (RPE) monolayer, Bruch’s-like membrane, and choroid capillaries with patent lumen and fenestration as well as M1 and/or M2 polarized macrophages. Our results indicate that the inclusion of macrophage in the model induces choroidal capillary growth. However, this model is unable to replenish macrophage cells during 5 – 6 weeks of maturation in culture, leading to their aging and senescence, which in turn causes capillary hyperproliferation in the sub-RPE space characteristic of type I nAMD. Our model helps to identify the role of immune cells in subclinical type I nAMD development and pathogenesis, providing a platform to explore drug therapies aimed at early disease prevention.

Scientific Focus Area: Biomedical Engineering and Biophysics

This page was last updated on Tuesday, August 6, 2024