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Teppei Shibata, Shinsuke Shibata, Dhirendra P Singh, Etsuko Kiyokawa, Masahito Ikawa, Hiroshi Sasaki, Eri Kubo; Age-related changes of the lens in Tropomyosin 1 conditional knockout mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5697. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Tropomyosin (Tpm) 1 and 2 each play an important role in the epithelial mesenchymal transition of lens epithelial cells. We analyzed the age-related changes in the crystalline lens in conditional Tpm 1 knockout (Tpm1-CKO) mice.
Floxed alleles of Tpm1 were conditionally deleted in the lens by using Pax6-cre transgenic mice (Tpm1-CKO). Lenses of 1-, 11- and 48-week-old Tpm1 CKO and wild-type mice (WT) as controls were dissected and photographed. Extracted lenses were fixed with paraffin and stained with hematoxylin-eosin. The immunological localizations of Tpm1/2, alpha-smooth muscle actin (α-SMA), and F-actin were determined. The expressions of Tpm2 and αSMA mRNAs were examined by RT-qPCR.
Among the homozygous Tpm1-CKO (Tpm 1−/−) lenses, lens opacity and a significant reduction of lens size were observed in the 1-week-old group. Disorder of lens fiber cells and cortical and peri-nuclear liquefaction were observed in the Tpm 1−/− lenses. In the heterozygous Tpm1-CKO (Tpm 1+/−) lenses, swelling of the lens fibers and the formation of vacuoles were observed in 11-week-old lenses. The progression of lens fiber damage in the Tpm 1+/− lenses was slower than that in the Tpm 1−/− lenses. In the 48-week-old group, the sizes of lenses were smaller than those in the WT group, and the lens fiber damage was further progressed compared to the 11-week-old lenses. Expression of F-actin in Tpm 1−/− and Tpm 1+/− was observed in damaged fiber cells and in all of the age groups. Expressions of Tpm 1/2 and αSMA mRNA were decreased in the Tpm 1−/− and Tpm 1+/− lenses.
Our results highlight the significance of Tpm1's function in lens fiber differentiation with aging. Dysregulation of Tpm1 during aging may induce lens opacity.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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