Dog as the experimental model: Laboratory uses of dogs in the United States.

Dogs are the experimental model in many types of biomedical research. Each year, hundreds of publications report the use of dogs in invasive biomedical procedures, often without sufficient explanation of the purpose and justification for selecting dog as the experimental model. The European Union requires detailed reporting of animal use that includes research purpose, but animal use reporting in the United States, overseen by the USDA, does not require this information. The ability to replace dogs with alternative models begins by understanding how they are used. Therefore, this study was undertaken to investigate the types of invasive biomedical procedures that dogs are subjected to in US laboratories. Well-defined sets of research publications and grants were accessed to obtain information on the types of biomedical research using dogs. USDA databases provided additional information. An ontology to categorize biomedical research uses of dogs identified the most common as translational studies for cardiovascular, cancer, nervous/mental, and mus-culoskeletal disorders. Information typically reported for experimental animals was sometimes missing or incomplete in publications, including the number, source, fate, species justification, and pain management of dogs, suggesting that many journals have not adopted the ARRIVE guidelines on animal use reporting. It was not possible to identify the research purpose for all dogs used by US institutions because (a) not all dog use is published and (b) animal research purpose is not required reporting in the US. These findings should be informative to future initiatives to replace, reduce, and refine the use of dogs in research.

Proposed new classification scheme for chemical injury to the human eye.

PURPOSE: Various ocular alkali burn classification schemes have been published and used to grade human chemical eye injuries for the purpose of identifying treatments and forecasting outcomes. The ILSI chemical eye injury classification scheme was developed for the additional purpose of collecting detailed human eye injury data to provide information on the mechanisms associated with chemical eye injuries. This information will have clinical application, as well as use in the development and validation of new methods to assess ocular toxicity. METHODS: A panel of ophthalmic researchers proposed the new classification scheme based upon current knowledge of the mechanisms of eye injury, and their collective clinical and research experience. Additional ophthalmologists and researchers were surveyed to critique the scheme. The draft scheme was revised, and the proposed scheme represents the best consensus from at least 23 physicians and scientists. RESULTS: The new scheme classifies chemical eye injury into five categories based on clinical signs, symptoms, and expected outcomes. Diagnostic classification is based primarily on two clinical endpoints: (1) the extent (area) of injury at the limbus, and (2) the degree of injury (area and depth) to the cornea. CONCLUSIONS: The new classification scheme provides a uniform system for scoring eye injury across chemical classes, and provides enough detail for the clinician to collect data that will be relevant to identifying the mechanisms of ocular injury.

Modulation of IL-8 and RANTES release in human conjunctival epithelial cells: primary cells and cell line compared and contrasted.

PURPOSE: Recent research indicates that epithelial cells of the ocular surface can contribute to the allergic reaction by the release of inflammatory and/or chemotactic mediators. In this study, the role of two inflammatory mediators, previously identified in the tear film of ocular allergy subjects, TNF-alpha and IFN-gamma, were evaluated for their effect on the release of two chemotactic mediators, IL-8 and RANTES, from cultured human conjunctival epithelial cells. METHODS: Human conjunctival epithelial cells (primary cells or HC0597 cell line) were grown to confluence and stimulated with various concentrations of TNF-alpha, IFN-gamma, or a combination of both. Supernatants were collected at 6, 24, and 48 hours and stored frozen for subsequent ELISA analyses of RANTES and IL-8. RESULTS: RANTES and IL-8 release from HC0597 cells was stimulated in a dose- and time-dependent manner following treatment with TNF-alpha. However, only RANTES release was modulated by IFN-gamma treatment. Treatment of HC0597 cells with both TNF-alpha and IFN-gamma resulted in a synergistic increase in the release of RANTES. This synergistic effect was confirmed using primary cultures of human conjunctival epithelial cells. CONCLUSIONS: Stimulation of conjunctival epithelium with proinflammatory mediators, TNF-alpha and/or IFN-gamma, generated the release of the chemotactic factors IL-8 and RANTES, which could act to prolong inflammation. These two chemokines may prolong inflammation by recruiting eosinophils to the ocular surface. This is the first study to compare chemokine release in a cell line and primary cells; similar chemokine release after mediator stimulation was demonstrated, indicating that the two cell types are phenotypically similar.