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. 2023 May 31:11:1164795.
doi: 10.3389/fbioe.2023.1164795. eCollection 2023.

The human lens is capable of trilineage differentiation towards osteo-, chondro-, and adipogenesis-a model for studying cataract pathogenesis

Gerard Boix-Lemonche  1 , Richard M Nagymihaly  2 , Xhevat Lumi  2   3   4 , Goran Petrovski  1   2   5
Affiliations

The human lens is capable of trilineage differentiation towards osteo-, chondro-, and adipogenesis-a model for studying cataract pathogenesis

Gerard Boix-Lemonche et al. Front Bioeng Biotechnol. .

Abstract

The potential for trilineage differentiation of cells in tissues represents a model for studying disease pathogenesis and regeneration pathways. Human lens trilineage differentiation has not yet been demonstrated, and so has calcification and osteogenic differentiation of human lens epithelial cells in the whole human lens. Such changes can pose a risk for complications during cataract surgery. Human lens capsules (n = 9) from cataract patients undergoing uneventful surgery were trilineage-differentiated toward osteogenesis, chondrogenesis, and adipogenesis. Furthermore, whole human healthy lenses (n = 3) collected from cadaveric eyes were differentiated into bone and characterized by immunohistochemistry. The cells in the human lens capsules were capable of undergoing trilineage differentiation, while the whole human healthy lenses could undergo osteogenesis differentiation, expressing osteocalcin, collagen I, and pigment epithelium-derived factor. We, hereby, show an ex vivo model for cataract formation through different stages of opacification, as well as provide in vivo evidence from patients undergoing calcified lens extraction with bone-like consistency.

Keywords: adipogenesis; cataract; chondrogenesis; human lens; osteogenesis; trilineage differentiation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Human lens capsule trilineage differentiation. Human lens capsules immersed in (A) chondrogenic differentiation media for 21 days, (B) osteogenic differentiation media for 21 days, and (C) adipogenic differentiation media for 21 days. The scale bars of the first two images in chondro- and osteogenesis measure 500 μm, while the rest of the scale bars measure 200 µm.
FIGURE 2
FIGURE 2
(A) Microscopic (aforementioned) and macroscopic (mentioned as follows) images of human lenses undergoing osteogenesis differentiation; (B) microscopic (aforementioned) and macroscopic (mentioned as follows) images of human lenses in complete DMEM/F-12.
FIGURE 3
FIGURE 3
Removal of a grade 3 cataract from a patient (A, B). The circle and the arrows indicate the position of the cataracted lens.
FIGURE 4
FIGURE 4
Immunohistological characterization of control human lenses (A—D; first row) and whole cultivated human lenses in osteogenic media for 28 days (E—H; second row) at 20X. Hematoxylin and eosin staining is shown in (A, E; first column), and staining for OCN (B, F; second column), collagen I (C, G; third column), and PEDF (D, H; fourth column). Presence of the protein is marked by the dark brown color.
See this image and copyright information in PMC

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References

    1. Alexander N., Walshe J., Richardson N. A., Futrega K., Doran M. R., Harkin D. G., et al. (2020). Stromal cells cultivated from the choroid of human eyes display a mesenchymal stromal cell (MSC) phenotype and inhibit the proliferation of choroidal vascular endothelial cells in vitro . Exp. Eye Res. 200, 108201. 10.1016/j.exer.2020.108201 - DOI - PubMed
    1. Allen D., Vasavada A. (2006). Cataract and surgery for cataract. BMJ 333, 128–132. 10.1136/bmj.333.7559.128 - DOI - PMC - PubMed
    1. Andley U. (2009). Effects of α-crystallin on lens cell function and cataract pathology. Curr. Mol. Med. 9, 887–892. 10.2174/156652409789105598 - DOI - PubMed
    1. Asbell P. A., Dualan I., Mindel J., Brocks D., Ahmad M., Epstein S. (2005). Age-related cataract. Lancet 365, 599–609. 10.1016/S0140-6736(05)17911-2 - DOI - PubMed
    1. Balogh E., Tóth A., Tolnai E., Bodó T., Bányai E., Szabó D. J., et al. (2016). Osteogenic differentiation of human lens epithelial cells might contribute to lens calcification. Biochim. Biophys. Acta - Mol. Basis Dis. 1862, 1724–1731. 10.1016/j.bbadis.2016.06.012 - DOI - PubMed

Grants and funding

This project was supported by grants from the European Union’s Horizon 2020 Research and Innovation program under the Marie Skłodowska-Curie Actions Grant agreement No 801133.

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