title: Extent of corneal injury as a biomarker for hazard assessment and the development of alternative models to the Draize rabbit eye test.
abstract: We have characterized 22 ocular irritants differing in type (surfactants, acid, alkali, bleaches, alcohol, aldehyde, acetone) and severity (slight to severe) by using the low-volume rabbit eye test. Ocular irritation was evaluated by 1) light microscopy to assess pathological changes, 2) in vivo confocal microscopy (CM) to quantify 4-dimensionally (x, y, z, and t) initial corneal injury and later responses in the same eye, and 3) laser scanning CM to quantify initial cell death. These studies revealed that regardless of the processes leading to injury, slight irritants injure the corneal epithelium, mild irritants injure the corneal epithelium and the superficial stroma, and moderate/severe irritants injure the epithelium, deep stroma, and at times the corneal endothelium. Furthermore, extent of initial corneal injury was shown to predict subsequent responses and final outcomes. These findings suggest that extent of corneal injury may be used as a basis for the development of alternative ocular irritation tests. To test the validity of this approach, we have used an ex vivo, rabbit cornea culture model to measure extent of corneal injury following exposure to ocular irritants. Data indicate that the extent of ex vivo corneal injury significantly correlate with the extent of initial injury measured previously in live animals. Overall, these findings indicate that extent of initial corneal injury can be used as a new "gold standard" for the continued refinement and ultimate replacement of the Draize rabbit eye Ocular Irritation Test.
authors.affiliation: Eye Institute, University of California at Irvine, Irvine, California 92868-4380, USA. jjester@uci.edu
authors.forename: James V
authors.initials: JV
authors.lastname: Jester
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D015415:Biomarkers; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D065306:Corneal Injuries; D005131:Eye Injuries / Q000139:chemically induced*; D066298:In Vitro Techniques; D007509:Irritants / Q000633:toxicity*; D018613:Microscopy, Confocal; D011817:Rabbits; D018570:Risk Assessment; D023382:Toxicity Tests, Acute / Q000379:methods*
chemical_list: D015415:Biomarkers; D007509:Irritants