Nonlinear Radiation-Induced Cataract Using the Radiosensitive Ptch1+/- Mouse Model

TitleNonlinear Radiation-Induced Cataract Using the Radiosensitive Ptch1+/- Mouse Model
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2016
AuthorsDe Stefano, Ilaria, Giardullo Paola, Tanno Barbara, Leonardi Simona, Pasquali Emanuela, Babini G., Saran Anna, and Mancuso Mariateresa
JournalRadiation Research
Keywordsallele, Alleles, animal, animal experiment, animal model, animal tissue, Animals, article, cataract, cataractogenesis, Cell Polarity, cell vacuole, controlled study, Crystalline, deficiency, disease model, Disease Models, Dose-Response Relationship, Female, Gene expression, genetics, histology, immunohistochemistry, lens, lens fiber, male, metabolism, Mice, mouse, nonhuman, Nonlinear Dynamics, nonlinear system, Patched-1 Receptor, Pathology, priority journal, protein expression, protein Patched 1, Radiation, radiation dose, Radiation Injuries, radiation injury, radiation response, Radiation Tolerance, radiosensitivity, Smad3 protein, sonic hedgehog protein, transcription factor Gli2, transforming growth factor beta, Western blotting

While most of the evidence for radiation-induced late health effects relates to cancer, there has been increasing interest recently in the development of non-cancer diseases, including lens opacity, observed in populations exposed to low-dose radiation. In a recent study, we reported that mice heterozygous for the Patched1 (Ptch1) gene represented a novel and powerful animal model for this disorder, and a useful tool for investigating the mechanisms of radiogenic cataract development. Given the ongoing and considerable uncertainty in allowable lens dose levels and the existence of a threshold for the development of cataracts, we tested the effects of a decreasing range of radiation doses (2 Gy, 1 Gy and 0.5 Gy X rays) by irradiating groups of Ptch1+/- mice at 2 days of age. Our findings showed that at this dose range, acute exposure of this highly susceptible mouse model did not induce macroscopically detectable cataracts, and only the 2 Gy irradiated mice showed microscopic alterations of the lens. Molecular analyses performed to evaluate the induction of epithelial-mesenchymal transition (EMT) and subsequent fibrotic alterations in mouse lens cells also indicated the existence of a dose threshold for such effects in the mouse model used. The mechanisms of cataractogenesis remain unclear, and further experimental studies are essential to elucidate those mechanisms specific for cataract initiation and development after irradiation, as well as the underlying genetic factors controlling cataract susceptibility. © 2016 by Radiation Research Society.


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