Department of Basic Sciences, University of Health Sciences and Pharmacy in St. Louis, 1 Pharmacy Place, St. Louis, MO 63110, USA.
Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8096, St. Louis, MO 63110, USA.
J R Soc Interface. 2023 Sep;20(206):20230316. doi: 10.1098/rsif.2023.0316. Epub 2023 Sep 20.
Vertebrate eye lenses are uniquely adapted to form a refractive index gradient (GRIN) for improved acuity, and to grow slowly in size despite constant cell proliferation. The mechanisms behind these adaptations remain poorly understood. We hypothesize that cell compaction contributes to both. To test this notion, we examined the relationship between lens size and shape, refractive characteristics and the cross-sectional areas of constituent fibre cells in mice of different ages. We developed a block-face imaging method to visualize cellular cross sections and found that the cross-sectional areas of fibre cells rose and then decreased over time, with the most significant reduction occurring in denucleating cells in the adult lens cortex, followed by cells in the embryonic nucleus. These findings help reconcile differences between the predictions of lens growth models and empirical data. Biomechanical simulations suggested that compressive forces generated from continuous deposition of fibre cells could contribute to cellular compaction. However, optical measurements revealed that the GRIN did not mirror the pattern of cellular compaction, implying that compaction alone cannot account for GRIN formation and that additional mechanisms are likely to be involved.
脊椎动物的晶状体经过独特的适应性进化,形成了折射率梯度(GRIN),从而提高了视力敏锐度,并且能够在持续增殖的同时缓慢生长。然而,这些适应性背后的机制仍知之甚少。我们假设细胞的紧凑化对此两者均有贡献。为了验证这一假说,我们研究了不同年龄小鼠晶状体大小和形状、折射特性以及组成纤维细胞的横截面积之间的关系。我们开发了一种块面成像方法来可视化细胞的横切面,结果发现纤维细胞的横截面积随时间的推移而增加,然后减少,在成年晶状体皮质的去核细胞中减少最为显著,随后是胚胎核中的细胞。这些发现有助于调和晶状体生长模型的预测与经验数据之间的差异。生物力学模拟表明,连续沉积纤维细胞产生的压缩力可能有助于细胞的紧凑化。然而,光学测量表明,GRIN 并没有反映细胞紧凑化的模式,这意味着仅仅紧凑化并不能解释 GRIN 的形成,可能还涉及其他机制。