Human corneal cell culture models for drug toxicity studies

Abstract

In vivo toxicity and absorption studies of topical ocular drugs are problematic, because these studies involve invasive tissue sampling and toxic effects in animal models. Therefore, different human corneal models ranging from simple monolayer cultures to three-dimensional models have been developed for toxicological prediction with in vitro models. Each system has its own set of advantages and disadvantages. Use of non-corneal cells, inadequate characterization of gene-expression profiles, and accumulation of genomic aberrations in human corneal models are typical drawbacks that decrease their reliability and predictive power. In the future, further improvements are needed for verifying comparable expression profiles and cellular properties of human corneal models with their in vivo counterparts. A rapidly expanding stem cell technology combined with tissue engineering may give future opportunities to develop new tools in drug toxicity studies. One approach may be the production of artificial miniature corneas. In addition, there is also a need to use large-scale profiling approaches such as genomics, transcriptomics, proteomics, and metabolomics for understanding of the ocular toxicity.

Corneal Tissue Engineering: An <em>In Vitro</em> Model of the Stromal-nerve Interactions of the Human Cornea

“…The 3D in vitro models are the most promising and of great scientific interest.3D models are known to better mirror the in vivo cellular and physiological events that are critical during fibrosis and wound healing 15,27,28,29 .These in vitro models play an integral role in finding new therapeutic approaches for treating different disease conditions including corneal complications. Despite the critical role of innervation in corneal functions, little effort has been made to promote peripheral nerve proliferation within corneal tissue-engineered constructs 2,3 . However, the proposed 3D in vitro cell constructs mimic the target tissue in order to attain the desired tissue functionality.…”

“…To address the demand for viable human corneas, significant progress in three-dimensional (3D) tissue engineering has been made 2,3,4 . These cornea models range from simple monolayer systems to multilayered models, leading to 3D full-thickness corneal equivalents 2 .…”

“…To address the demand for viable human corneas, significant progress in three-dimensional (3D) tissue engineering has been made 2,3,4 . These cornea models range from simple monolayer systems to multilayered models, leading to 3D full-thickness corneal equivalents 2 . However, the use of a 3D tissue-engineered cornea in the context of in vitro disease models studied to date lacks resemblance to the multilayered 3D corneal tissue structure, function, and the networking of different cell types ( i.e. , nerve, epithelium, stroma, and endothelium) 2,3 .In addition, the demand for in vitro cornea tissue models has increased in an attempt to reduce animal testing for pharmaceutical products.…”

“…These cornea models range from simple monolayer systems to multilayered models, leading to 3D full-thickness corneal equivalents 2 .…”

“…, nerve, epithelium, stroma, and endothelium) 2,3 .In addition, the demand for in vitro cornea tissue models has increased in an attempt to reduce animal testing for pharmaceutical products. Thus, more sophisticated models are required to better match systems to human physiological requirements, and the development of a model that is more relevant to the patient population is absolutely necessary.…”