In vitro models for ocular injury: Current and potential biomarkers

C Eskes¹, DG Allen², RR Tice², NY Choksi², JF Truax², W Chambers³, WS Stokes⁴, LM Schechtman³

1. European Commission DG Joint Research Centre, Ispra, Italy
2. Intergrated Laboratory Systems, Inc. RTP, NC, USA
3. U.S. FDA, Rockville, MD, USA
4. NICEATM, NIEHS, RTP, NC, USA

Numerous in vitro / ex vivo methods for eye irritation have been developed and are currently being used within industry for specific purposes. In vitro model systems for eye irritation can be divided into four major categories: organotypic models, human corneal epithelium models, cell cytotoxicity assays and cell function assays. The biomarkers and mechanisms usually addressed range from simple cytotoxicity to more complex functional endpoints such as corneal light transmission and barrier functions. However, the range of criteria for injury, inflammation and reversibility covered by the Draize rabbit eye test was found to be unlikely to be replaced by a single in vitro test. One of the recommendations to achieve full animal replacement is to support the development of mechanistically-based models in order to address the mechanisms not currently covered by the existing assays. During the ICCVAM-NICEATM-ECVAM symposium on Mechanisms of Chemically-Induced Ocular Injury and Recovery (May 11-12, 2005), novel and existing biomarkers were identified that may allow further mechanistic insight into the ocular irritancy potential of a test substance. Discussions addressed the potential in vitro test systems and biomarkers that may allow adequate prediction of the mechanisms of chemically-induced ocular injury and lesion persistence versus reversibility. Finally, novel in vitro biomarkers or test systems were identified where further research and development is recommended to investigate the correlation with the in vivo test. ILS staff supported by NIEHS contract N01-ES 35504.

Date: Monday, August 22, 2005, 11.30-13.30 h, ECC Hall D

5.11 Workshop: Mechanisms of Chemically-induced Ocular Injury and Recovery: Current Understanding and Research Needs.