3D In Vitro Model of the RPE-Choriocapillaris Complex

Article: First-ever lab model of human eye offers hope for macular degeneration patients
Source: University of Rochester, via NEI
Published: March 29, 2021
Article: 3D Lab Model Developed in Search for New Therapies for AMD
Source: Genetic Engineering & Biotechnology News
Published: April 1, 2021

Illustration of a 3D model of the RPE-choriocapillaris complex

To better understanding the underlying pathology of age-related macular degeneration (AMD), researchers at the University of Rochester have engineered a 3D in vitro model of the RPE-choriocapillaris complex of the human retina. In designing a more accurate in vitro model of the human retina, they sought to resolve a debate in the field as to whether the etiology of macular degeneration is due to defects in the retina or due to systemic issues, such as blood supply. Their model combines induced pluripotent stem cell-derived retinal tissue from human patients with a hydrogel-based extracellular matrix to better replicate the relationship between the retinal pigment epithelium (RPE) and the underlying vasculature of the choriocapillaris (CC). Notably, their model confirmed that RPE and mesenchymal stem cells play a role in the development of the choriocapillaris layer, showed that blood-derived factors from patients can independently contribute to the development and progression of wet AMD, and identified FGF2 (a fibroblast growth factor) and matrix metalloproteinases as potential therapeutic targets for AMD and other macular dystrophies. In answer to the initiating question regarding AMD etiology, their retinal model strongly points to retinal defects, particularly the RPE, as contributing to AMD. One of the researchers explains, “You can have completely normal choriocapillaris, but if your RPE’s are dysfunctional it will cause the choriocapillaris to dysfunction.” Once the model has been validated in larger sample sizes, they hope it would be useful in testing and developing drug therapies specific to individual patients.

My rating of this study: ⭐⭐⭐

Manian KV, Galloway CA, Dalvi S, et al. "3D iPSC modeling of the retinal pigment epithelium-choriocapillaris complex identifies factors involved in the pathology of macular degeneration." Cell Stem Cell.  29 March 2021. https://doi.org/10.1016/j.stem.2021.02.006