The long-term objective of this project is to understand and manipulate induced corneal angiogenesis and neoplasia in the laboratory opossum (Monodelphis domestica) model. Monodelphis is a particularly promising model because angiogenesis and neoplasia of the cornea can be produced using ultraviolet radiation (UVR) without surgical manipulation. More that 60% of Monodelphis develop neoplasia after UVR exposure, which is a highly heritable trait. Angiogenesis is a finely regulated process that is essential for development, the pathogenesis of a number of human diseases including but not limited to rheumatoid arthritis, birth marks, psoriasis, and neoplasia. Pathological angiogenesis is a common feature of many eye diseases and is the most frequent cause of blindness in humans. The development of a Monodelphis model to study angiogenesis may provide new approaches for diagnosis and treatment of angiogenic diseases in humans. The first specific aim is to identify pathological changes in the eye induced by UV irradiation that are associated with angiogenesis and neoplasia in the corneal (mesenchymal) stroma. The second specific aim is to stimulate angiogenesis with exogenous agents in opossum corneas exposed to UV irradiation and to assess the impact on neoplasia. The third specific aim would be to block corneal angiogenesis with exogenous inhibitors in opossum corneas exposed to UV irradiation and to assess the impact on neoplasia. The research design consists of 200 opossums divided into groups composed of approximately equal numbers of randomly selected young adults of both sexes as follows: Group 1 - irradiate animals with whole body exposure to 125 J/m2 of UV-B (spectral peak of 302 nm) three times a week for up to 45 weeks to study corneal changes induced by UVR; Group 2- impact on neoplasia; Group 3- block corneal angiogenesis with exogenous inhibitors during UV irradiation and assess impact on neoplasia. Evaluations at predetermined time points will be numerically graded for statistical evaluation and include visual unaided, stereomicroscopic, and histologic (light microscopy and selected transmission electron microscopy) assessments, and immunochemistry. The laboratory opossum is a promising, emerging model for corneal angiogenesis and neoplasia and promises to contribute significantly to the investigation of these processes.
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