Wu Weiju, Lois Noemi, Prescott Alan R, Brown Adrian P, Van Gerwen Veerle, Tassignon Marie-José, Richards Shane A, Saunter Christopher D, Jarrin Miguel, Quinlan Roy A
Department of Biosciences, South Road, Durham University, Durham, DH1 3LE, England, UK.
Wellcome-Wolfson Institute for Experimental Medicine, Queens University Belfast, 97 Lisburn Rd, Belfast, BT9 7BL, Northern Ireland, UK.
Exp Eye Res. 2021 Dec;213:108808. doi: 10.1016/j.exer.2021.108808. Epub 2021 Nov 9.
Human lens regeneration and the Bag-in-the-Lens (BIL) surgical treatment for cataract both depend upon lens capsule closure for their success. Our studies suggest that the first three days after surgery are critical to their long-term outcomes. Using a rat model of lens regeneration, we evidenced lens epithelial cell (LEC) proliferation increased some 50 fold in the first day before rapidly declining to rates observed in the germinative zone of the contra-lateral, un-operated lens. Cell multi-layering at the lens equator occurred on days 1 and 2, but then reorganised into two discrete layers by day 3. E- and N-cadherin expression preceded cell polarity being re-established during the first week. Aquaporin 0 (AQP0) was first detected in the elongated cells at the lens equator at day 7. Cells at the capsulotomy site, however, behaved very differently expressing the epithelial mesenchymal transition (EMT) markers fibronectin and alpha-smooth muscle actin (SMA) from day 3 onwards. The physical interaction between the apical surfaces of the anterior and posterior LECs from day 3 after surgery preceded cell elongation. In the human BIL sample fibre cell formation was confirmed by both histological and proteome analyses, but the cellular response is less ordered and variable culminating in Soemmerring's ring (SR) formation and sometimes Elschnig's pearls. This we evidence for lenses from a single patient. No bow region or recognisable epithelial-fibre cell interface (EFI) was evident and consequently the fibre cells were disorganised. We conclude that lens cells require spatial and cellular cues to initiate, sustain and produce an optically functional tissue in addition to capsule integrity and the EFI.
人类晶状体再生以及用于治疗白内障的“透镜袋”（BIL）手术的成功均取决于晶状体囊的闭合。我们的研究表明，手术后的头三天对其长期结果至关重要。使用晶状体再生的大鼠模型，我们证明晶状体上皮细胞（LEC）增殖在第一天增加了约50倍，然后迅速下降至对侧未手术晶状体生发区观察到的速率。晶状体赤道处的细胞多层化在第1天和第2天出现，但到第3天重新组织成两个离散的层。E-钙黏蛋白和N-钙黏蛋白的表达先于第一周内细胞极性的重新建立。水通道蛋白0（AQP0）在第7天首次在晶状体赤道处的伸长细胞中被检测到。然而，囊切开部位的细胞表现非常不同，从第3天起就表达上皮-间质转化（EMT）标志物纤连蛋白和α-平滑肌肌动蛋白（SMA）。手术后第3天起，前后LEC顶端表面之间的物理相互作用先于细胞伸长。在人类BIL样本中，通过组织学和蛋白质组分析均证实了纤维细胞的形成，但细胞反应较无序且多变，最终形成索默林环（SR），有时还会形成埃尔施尼格珠。我们以一名患者的晶状体为例证明了这一点。没有明显的弓形区域或可识别的上皮-纤维细胞界面（EFI），因此纤维细胞排列紊乱。我们得出结论，除了囊膜完整性和EFI外，晶状体细胞还需要空间和细胞线索来启动、维持并产生具有光学功能的组织。
