Department of Ophthalmology, Kanazawa Medical University, Ishikawa, Japan.
Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Mech Ageing Dev. 2021 Jun;196:111492. doi: 10.1016/j.mad.2021.111492. Epub 2021 Apr 15.
Tropomyosin (Tpm) 1 and 2 are important in the epithelial mesenchymal transition of lens epithelial cells; however, the effect of Tpm1 depletion during aging remains obscure. We analyzed the age-related changes in the crystalline lens of Tpm1- conditional knockout mice (Tpm1-CKO). Floxed alleles of Tpm1 were conditionally deleted in the lens, using Pax6-cre transgenic mice. Lenses of embryonic day (ED) 14, postnatal 1-, 11-, and 48-week-old Tpm1-CKO and wild type mice were dissected to prepare paraffin sections, which subsequently underwent histological and immunohistochemical analysis. Tpm1 and α smooth muscle actin (αSMA) mRNA expression were assessed using RT-PCR. The homozygous Tpm1-CKO (Tpm1) lenses displayed a dramatic reduction in Tpm1 transcript, with no change to αSMA mRNA expression. Tpm1 mice had small lenses with disorganized, vesiculated fiber cells, and loss of epithelial cells. The lenses of Tpm1 mice had abnormal and disordered lens fiber cells with cortical and peri-nuclear liquefaction. Expression of filamentous-actin was reduced in the equator region of lenses derived from ED14, 1-, 11-, and 48-week-old Tpm1 mice. Therefore, Tpm1 plays an integral role in mediating the integrity and fate of lens fiber differentiation and lens homeostasis during aging. Age-related Tpm1 dysregulation or deficiency may induce cataract formation.
原肌球蛋白 (Tpm) 1 和 2 在晶状体上皮细胞的上皮间质转化中很重要；然而，Tpm1 在衰老过程中耗竭的影响仍不清楚。我们分析了 Tpm1 条件性敲除小鼠（Tpm1-CKO）晶状体的年龄相关性变化。使用 Pax6-cre 转基因小鼠在晶状体中条件性敲除 Tpm1 的 floxed 等位基因。从胚胎期 14 天 (ED)、出生后 1 周、11 周和 48 周的 Tpm1-CKO 和野生型小鼠中分离出晶状体，制备石蜡切片，随后进行组织学和免疫组织化学分析。使用 RT-PCR 评估 Tpm1 和 α 平滑肌肌动蛋白 (αSMA) mRNA 的表达。纯合 Tpm1-CKO (Tpm1) 晶状体的 Tpm1 转录物明显减少，而 αSMA mRNA 表达没有变化。Tpm1 小鼠的晶状体较小，纤维细胞排列紊乱，上皮细胞缺失。Tpm1 小鼠的晶状体纤维细胞异常排列，皮质和核周液化。从 ED14、1 周、11 周和 48 周龄的 Tpm1 小鼠晶状体的赤道区，丝状肌动蛋白的表达减少。因此，Tpm1 在介导晶状体纤维分化和衰老过程中的晶状体内稳态的完整性和命运中起着不可或缺的作用。与年龄相关的 Tpm1 失调或缺乏可能会导致白内障形成。
