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The long-term effect of low and moderate doses of ionizing radiation on the lens is still a matter of debate and needs to be evaluated in more detail. We conducted a detailed histological analysis of eyes from B6C3F1 mice cohorts after acute gamma irradiation (60Co source; 0.063 Gy/min) at young adult age of 10 weeks with doses of 0.063, 0.125, and 0.5 Gy. Sham irradiated (0 Gy) mice were used as controls. To test for genetic susceptibility heterozygous Ercc2 mutant mice were used and compared to wild-type mice of the same strain background. Mice of both sexes were included in all cohorts. Eyes were collected 4 h, 12, 18 and 24 months after irradiation. For a better understanding of the underlying mechanisms, metabolomics analyses were performed in lenses and plasma samples of the same mouse cohorts at 4 and 12 h as well as 12, 18 and 24 months after irradiation. For this purpose, a targeted analysis was chosen. This analysis revealed histological changes particularly in the posterior part of the lens that rarely can be observed by using Scheimpflug imaging, as we reported previously. We detected a significant increase of posterior subcapsular cataracts (PSCs) 18 and 24 months after irradiation with 0.5 Gy (odds ratio 9.3; 95% confidence interval 2.1–41.3) independent of sex and genotype. Doses below 0.5 Gy (i.e. 0.063 and 0.125 Gy) did not significantly increase the frequency of PSCs at any time point. In lenses, we observed a clear effect of sex and aging but not of irradiation or genotype. While metabolomics analyses of plasma from the same mice showed only a sex effect. This article demonstrates a significant radiation-induced increase in the incidence of PSCs, which could not be identified using Scheimpflug imaging as the only diagnostic tool. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the localization of endostatin, a potent angiogenesis inhibitor, and its progenitor collagen XVIII in the human eye. Methods: Twelve normal human eyes were investigated. Immunohistochemistry of the anterior and posterior eye segment was performed using a polyclonal endostatin and collagen XVIII antibody and a monoclonal collagen XVIII antibody. Specificity of the antibodies was confirmed by Western blot analysis. Results: The antibody against collagen XVIII stained Bowman's membrane, the lens capsule, the trabecular meshwork, and all epithelial and endothelial basal membranes in the anterior and posterior eye segment. In contrast, the antibody against endostatin showed a more distinct staining pattern. Intense intracellular staining for endostatin was present in the lens epithelium and in the nonpigmented epithelium of the ciliary body. Extracellular presence of endostatin could be detected in the lens capsule and all border membranes lining the aqueous humor including the anterior surface of the iris. The choroid was unstained. In the retina, staining was restricted to the inner limiting membrane and to endothelial cells of larger vessels. Conclusions: Our results show that there is a ring of specifically endostatin expressing structures forming a "barrier" around the anterior chamber and the vitreous. This might physiologically prevent vessels from sprouting into these avascular compartments. [ABSTRACT FROM AUTHOR]