Expression of transforming growth factor β and fibroblast growth factor 2 in the lens epithelium of <scp>M</scp>orioka cataract mice

Kondo, Tomohiro; Ishiga-Hashimoto, Naoko; Nagai, Hiroaki; Takeshita, Ai; Mino, Masaki; Morioka, Hiroshi; Kusakabe, Ken Takeshi; Okada, Toshiya

doi:10.1111/cga.12042

Cited by 4 publications

(1 citation statement)

References 26 publications

(57 reference statements)

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“…At the lens equator, however, epithelial cells in the posterior chamber are regularly exposed to elevated levels of FGF, and regardless of any increased TGF-β levels, the cells here likely undergo aberrant fibre differentiation, leading to pearl PCO. This may result from the heightened sensitivity to FGF of these peripheral LECs, namely due to their elevated levels of high-affinity FGF receptor tyrosine kinase (RTK) receptors, compared to the central lens epithelia [ 6 , 58 , 80 , 81 ]. In situ, during lens fibrosis, we do not see EMT resulting in cell death, likely due to survival growth factors present within the ocular media.…”

Section: Discussionmentioning

confidence: 99%

FGF-2 Differentially Regulates Lens Epithelial Cell Behaviour during TGF-β-Induced EMT

Flokis

Lovicu

2023

Cells

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Fibroblast growth factor (FGF) and transforming growth factor-beta (TGF-β) can regulate and/or dysregulate lens epithelial cell (LEC) behaviour, including proliferation, fibre differentiation, and epithelial–mesenchymal transition (EMT). Earlier studies have investigated the crosstalk between FGF and TGF-β in dictating lens cell fate, that appears to be dose dependent. Here, we tested the hypothesis that a fibre-differentiating dose of FGF differentially regulates the behaviour of lens epithelial cells undergoing TGF-β-induced EMT. Postnatal 21-day-old rat lens epithelial explants were treated with a fibre-differentiating dose of FGF-2 (200 ng/mL) and/or TGF-β2 (50 pg/mL) over a 7-day culture period. We compared central LECs (CLECs) and peripheral LECs (PLECs) using immunolabelling for changes in markers for EMT (α-SMA), lens fibre differentiation (β-crystallin), epithelial cell adhesion (β-catenin), and the cytoskeleton (alpha-tropomyosin), as well as Smad2/3- and MAPK/ERK1/2-signalling. Lens epithelial explants cotreated with FGF-2 and TGF-β2 exhibited a differential response, with CLECs undergoing EMT while PLECs favoured more of a lens fibre differentiation response, compared to the TGF-β-only-treated explants where all cells in the explants underwent EMT. The CLECs cotreated with FGF and TGF-β immunolabelled for α-SMA, with minimal β-crystallin, whereas the PLECs demonstrated strong β-crystallin reactivity and little α-SMA. Interestingly, compared to the TGF-β-only-treated explants, α-SMA was significantly decreased in the CLECs cotreated with FGF/TGF-β. Smad-dependent and independent signalling was increased in the FGF-2/TGF-β2 co-treated CLECs, that had a heightened number of cells with nuclear localisation of Smad2/3 compared to the PLECs, that in contrast had more pronounced ERK1/2-signalling over Smad2/3 activation. The current study has confirmed that FGF-2 is influential in differentially regulating the behaviour of LECs during TGF-β-induced EMT, leading to a heterogenous cell population, typical of that observed in the development of post-surgical, posterior capsular opacification (PCO). This highlights the cooperative relationship between FGF and TGF-β leading to lens pathology, providing a different perspective when considering preventative measures for controlling PCO.

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Section: Discussionmentioning

confidence: 99%

FGF-2 Differentially Regulates Lens Epithelial Cell Behaviour during TGF-β-Induced EMT

Flokis

Lovicu

2023

Cells

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A novel spontaneous mutation of BCAR3 results in extrusion cataracts in CF#1 mouse strain

et al. 2016

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A substrain of mice originating from the CF#1 strain (an outbred colony) reared at Osaka Prefecture University (CF#1/lr mice) develops cataracts beginning at 4 weeks of age. Affected mice were fully viable and fertile and developed cataracts by 14 weeks of age. Histologically, CF#1/lr mice showed vacuolation of the lens cortex, swollen lens fibers, lens rupture and nuclear extrusion. To elucidate the mode of inheritance, we analyzed heterozygous mutant hybrids generated from CF#1/lr mice and wild-type BALB/c mice. None of the heterozygous mutants were affected, and the ratio of affected to unaffected mice was 1:3 among the offspring of the heterozygous mutants. For the initial genome-wide screening and further mapping, we used affected progeny of CF#1/lr × (CF#1/lr × BALB/c) mice. We concluded that the cataracts in CF#1/lr mice are inherited through an autosomal recessive mutation and that the mutant gene is located on mouse chromosome 3 between D3Mit79 and D3Mit216. In this region, we identified 8 genes associated with ocular disease. All 8 genes were sequenced and a novel point mutation (1 bp insertion of cytosine) in exon 7 of the Bcar3 gene was identified. This mutation produced a premature stop codon and a truncated protein. In conclusion, we have identified the first spontaneous mutation in the Bcar3 gene associated with lens extrusion cataracts. This novel cataract model may provide further knowledge of the molecular biology of cataractogenesis and the function of the BCAR3 protein.

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Expressions of TGF-β2, bFGF and ICAM-1 in lens epithelial cells of complicated cataract with silicone oil tamponade

et al. 2017

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Expression of transforming growth factor β and fibroblast growth factor 2 in the lens epithelium of Morioka cataract mice

Cited by 4 publications

References 26 publications

FGF-2 Differentially Regulates Lens Epithelial Cell Behaviour during TGF-β-Induced EMT

FGF-2 Differentially Regulates Lens Epithelial Cell Behaviour during TGF-β-Induced EMT

A novel spontaneous mutation of BCAR3 results in extrusion cataracts in CF#1 mouse strain

Expressions of TGF-β2, bFGF and ICAM-1 in lens epithelial cells of complicated cataract with silicone oil tamponade

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