Ocular toxicity and irritancy testing in nonhuman animals is severely limited because most conventional tests are subjective, invasive, painful and nonreproducible. Although numerous alternatives have been proposed and heroic international efforts have been exerted; the validation of these methods has remained elusive. A novel compact dynamic light scattering (DLS) instrument, developed at NASA, offers significant mitigation to these limitations. In our pilot studies, we have demonstrated the feasibility of DLS for lens opacity and corneal irritancy measurement in rodents and rabbits in a way that is both reliable and relevant. The data output of DLS reflects the biological mechanisms of decreased corneal epithelial integrity and alteration or change of protein structure. In phase I of our project, we propose further study to optimize and develop DLS as a practical, reproducible and relevant technique applicable to study a wide variety of toxicants, to provide for diminution of pain or distress in ocular testing and to reduce the number of nonhuman animal subjects required for dependable testing We expect that this development will provide for a more humane, expedient and practical alternative in the short term; and a valuable tool for facilitating validation of in vitro tests in the long term.
The need for measuring ocular toxicity and irritancy is immense (see section B) and so there is a large market for the proposed method. The proposed technique is expected to provide a rapid, precise, non-invasive, non-painful and more biologically relevant alternative to the current techniques. Also the system could be used in research laboratories as an aid to the validation of other alternative methods.
