An overview of current alternative models in the context of ocular surface toxicity

Abstract

The 21st century has seen a steadily increasing social awareness of animal suffering, with increased attention to ethical considerations. Developing new integrated approaches to testing and assessment (IATA) strategies is an Organisation for Economic Co‐operation and Development (OECD) goal to reduce animal testing. Currently, there is a lack of alternative models to test for ocular surface toxicity (aside from irritation) in lieu of the Draize eye irritation test (OECD guideline No. 405) performed in rabbits. Five alternative in vitro or ex vivo methods have been validated to replace this reference test, but only in combination. However, pathologies like Toxicity‐Induced Dry Eye (TIDE), cataract, glaucoma, and neuropathic pain can occur after exposure to a pharmaceutical product or chemical and therefore need to be anticipated. To do so, new models of lacrimal glands, lens, and neurons innervating epithelia are required. These models must take into account real‐life exposure (dose, time, and tear film clearance). The scientific community is working hard to develop new, robust, alternative, in silico, and in vitro models, while attempting to balance ethics and availability of biological materials. This review provides a broad overview of the validated methods for analyzing ocular irritation and those still used by some industries, as well as promising models that need to be optimized according to the OECD. Finally, we give an overview of recently developed innovative models, which could become new tools in the evaluation of ocular surface toxicity within the scope of IATAs.

An Assessment of the Ocular Toxicity of Two Major Sources of Environmental Exposure

“…The in vivo methods are expensive and time consuming [ 57 ]. The in silico models are well adapted for a rapid analysis of identified chemicals [ 58 , 59 ]. Of these three, we applied an in silico model for this study as it is practical and widely applied in studies of chemical exposure toxicity [ 60 , 61 ].…”

Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases

“…The safety and effectiveness of the intelligent NIM delivery systems have been evaluated in cell culture and eye organ models in vitro and animal models. New Zealand white rabbits are the most common animal models because they are inexpensive, easy to obtain, and have been used in international standard tests evaluating the acute toxicity of ophthalmic drugs [ 101 , 102 ]. The primary sources of in vitro models of ocular organs are isolated rabbit, chicken, bovine, and porcine eyes.…”

Toxic External Exposure Leading to Ocular Surface Injury

“…Although incapable of replacing the Draize test entirely, in vitro tests have largely supplanted the Draize test as they are simple, reproducible, and inexpensive indicators of ocular toxicity [ 12 ]. The usage of human cell cultures from the corneal epithelium in many in vitro models allows for an accurate representation of the in vivo human response to toxic substances.…”