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K. Tsubota, K. Mishima, H. Inoue, H. Yamada, I. Saito; Clusterin is the Lacrimal Gland Side Population Secretory Glycoprotein and Can Restore Lacrimal Gland Function Through Suppressing Reactive Oxygen Species; A Potential New Therapy for Age-Related Dry Eye Disorders. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5655.
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© ARVO (1962-2015); The Authors (2016-present)
We found that clusterin is the lacrimal gland (LG) side population (SP) cell specific gene, which can restore hypofunction through the control of reactive oxygen species (ROS).
SP cells were purified from the LG of heterozygous enhanced green fluorescent protein (EGFP)-transgenic (GFP-Tg) mice of a C57BL/6 background. The cells were then injected with a microinjector directly into the LG of each experimental mouse two weeks after they were irradiated. The mice were sacrificed for analysis 8 weeks after the injection and the engrafted cells were identified by the presence of GFP and transplanted them into mice with irradiation-induced hypofunction in LG. Intracellular levels of ROS were assayed using the fluorescent indicator dichlorofluorescein diacetate.
The results revealed that the secretions from LG in the recipient mice were restored within two months after the transplantation, although transplanted cells were only sparsely distributed and produced no outgrowths, indicating that soluble factors secreted by SP cells, and not reconstituted cells, possibly restored the functions of the residual glands. We found that clusterin is the SP cell-specific secretory glycoprotein, and rescue cell death through the suppression of ROS accumulation induced by irradiation or oxidative stress.
Our results indicate that the benefits of SP cell transplantation are attributable to not cell transplantation mediated reconstitution of the glands but the functions of SP cell-derived soluble factor; clusterin. We propose that SP cells in each organ also might have specific factors that prevent cell stress, including oxidative stress. Here we provide initial evidence suggesting the possibility of clinical application of SP cell-related factor; clusterin, to treat oxidative-stress related aging diseases, including age-related dry eyes disorders.
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