Induction of Irritation and Inflammation in a 3D Innervated Tissue Model of the Human Cornea

Detection of slight changes in the chemical, thermal, and physical environments of the ocular surface is necessary to protect eyesight. The cornea, as the most densely innervated peripheral tissue in the body, can be damaged as a result of caustic chemical exposure. Such damage can be painful and debilitating, thus underscoring the need to understand mechanisms of ocular irritation. Both ethical and translational limitations regarding the use of animal subjects in part drive the need to develop relevant in vitro cell and tissue models that emulate the physiology of the human cornea. In this study, we utilized our 3D in vitro cornea-like tissue model to study the effects of irritation mediated by transient receptor potential (TRP) channels vanilloid 1 and ankyrin 1 (TRPV1; TRPA1) in response to allyl isothiocyanate (AITC) stimulation. Changes in gene expression were analyzed to characterize wound healing responses of the epithelial, stromal, and neuronal cell populations in the corneal tissue models. Key findings of the study include indications of wound healing, such as stromal myofibroblast differentiation and epithelial barrier re-establishment, amplification of pro-inflammatory cytokines, and downstream ECM protein remodeling due to irritation with the addition of sensory innervation. This study further establishes this in vitro tissue model as a useful tool for studying corneal irritation in vitro in a holistic manner with promise as a novel and sensitive tool for studying chemical exposures and subsequent responses.