Improved Ocular Tissue Models and Eye-On-A-Chip Technologies Will Facilitate Ophthalmic Drug Development

Abstract

In this study, we describe efforts by the National Eye Institute (NEI) and National Center for Advancing Translational Science (NCATS) to catalyze advances in 3-dimensional (3-D) ocular organoid and microphysiological systems (MPS). We reviewed the recent literature regarding ocular organoids and tissue chips. Animal models, 2-dimensional cell culture models, and postmortem human tissue samples provide the vision research community with insights critical to understanding pathophysiology and therapeutic development. The advent of induced pluripotent stem cell technologies provide researchers with enticing new approaches and tools that augment study in more traditional models to provide the scientific community with insights that have previously been impossible to obtain. Efforts by the National Institutes of Health (NIH) have already accelerated the pace of scientific discovery, and recent advances in ocular organoid and MPS modeling approaches have opened new avenues of investigation. In addition to more closely recapitulating the morphologies and physiological responses of in vivo human tissue, key breakthroughs have been made in the past year to resolve long-standing scientific questions regarding tissue development, molecular signaling, and pathophysiological mechanisms that promise to provide advances critical to therapeutic development and patient care. 3-D tissue culture modeling and MPS offer platforms for future high-throughput testing of therapeutic candidates and studies of gene interactions to improve models of complex genetic diseases with no well-defined etiology, such as age-related macular degeneration and Fuchs' dystrophy.

Keywords: microphysiological systems; organoid; tissue chip.

FIG. 1.

Retinal organoid publications by year. The number of publications featuring or using retina organoids as an experimental tool each year from 2014 through September 2018 is shown. Publications were identified using “retinal organoid,” “retinal sheet,” “retinal neurosphere,” “retinal spheroid,” and “optic vesicle-like” as search terms in PubMed on Sept. 20, 2018. Unique publications were identified by PMID, and redundant search results were excluded from consideration.