Type I Collagen Accelerates the Spreading of Lens Epithelial Cells through the Expression and Activation of Matrix Metalloproteinases

Shimada, Arata; Miyata, Yoshiki; Kosano, Hiroshi

doi:10.3109/02713683.2013.853194

Cited by 11 publications

(10 citation statements)

References 57 publications

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“…The normal lens capsule is mainly composed of laminin (LM) and type IV collagen [17–19]. Type I collagen is not detected in the capsule of normal lenses [20]. However, Type I collagen is expressed in cataractous lenses [21,22], and increases with age in human lens capsules [23].…”

Section: Introductionmentioning

confidence: 99%

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Laminin α4 overexpression in the anterior lens capsule may contribute to the senescence of human lens epithelial cells in age-related cataract

Sun

et al. 2019

Aging

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Senescence is a leading cause of age-related cataract (ARC). The current study indicated that the senescence-associated protein, p53, total laminin (LM), LMα4, and transforming growth factor-beta1 (TGF-β1) in the cataractous anterior lens capsules (ALCs) increase with the grades of ARC. In cataractous ALCs, patient age, total LM, LMα4, TGF-β1, were all positively correlated with p53. In lens epithelial cell (HLE B-3) senescence models, matrix metalloproteinase-9 (MMP-9) alleviated senescence by decreasing the expression of total LM and LMα4; TGF-β1 induced senescence by increasing the expression of total LM and LMα4. Furthermore, MMP-9 silencing increased p-p38 and LMα4 expression; anti-LMα4 globular domain antibody alleviated senescence by decreasing the expression of p-p38 and LMα4; pharmacological inhibition of p38 MAPK signaling alleviated senescence by decreasing the expression of LMα4. Finally, in cataractous ALCs, positive correlations were found between LMα4 and total LM, as well as between LMα4 and TGF-β1. Taken together, our results implied that the elevated LMα4, which was possibly caused by the decreased MMP-9, increased TGF-β1 and activated p38 MAPK signaling during senescence, leading to the development of ARC. LMα4 and its regulatory factors show potential as targets for drug development for prevention and treatment of ARC.

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Section: Introductionmentioning

confidence: 99%

“…In addition, numerous LM peptides were able to induce MMP-9 expression [45,46]. LECs cultured on type I collagen-coated dishes exhibited high expression levels of the pro-form of MMP-9 [20]. However, there is currently no evidence that shows a potential role of MMP-9 in senescent LECs or in senescent lens capsules of ARC.…”

Section: Introductionmentioning

confidence: 99%

Laminin α4 overexpression in the anterior lens capsule may contribute to the senescence of human lens epithelial cells in age-related cataract

Sun

et al. 2019

Aging

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“…Elschnig pearls and Soemmering ring) [27]. Furthermore, it can accelerate fibrosis by direct interaction with lens epithelial cells through metallo-matrix proteinases in lens epithelial cells [28]. This might explain why its presence is higher in the capsular folds, where fibrosis is increased.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of posterior capsule opacification of the Alcon Clareon IOL vs the Alcon Acrysof IOL using a human capsular bag model

et al. 2020

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Background: Posterior capsule opacification (PCO) after cataract surgery is influenced by intraocular lens (IOL) design and material. The following is an ex vivo comparison of PCO between the Clareon vs. the AcrySof IOL in human capsular bags. Methods: Twenty cadaver capsular bags from 10 human donors were used, with the novel hydrophobic IOL (Clareon, CNA0T0) being implanted in one eye and the other eye of the same donor receiving the AcrySof IOL (SN60WF) following phacoemulsification cataract surgery. Five capsular bags of 3 donors served as controls without IOL. Cellular growth of lens epithelial cells was photo-documented daily. The primary endpoint was the time until full coverage of the posterior capsule by cells. Furthermore, immunofluorescence staining of capsular bags for the fibrotic markers f-actin, fibronectin, alpha smooth muscle actin, and collagen type 1 were performed. Results: The new Clareon IOL did not show any disadvantages in terms of days until full cell coverage of the posterior capsule in comparison to the AcrySof (p > 0.99). Both, the Clareon (p = 0.01, 14.8 days) and the AcrySof IOL (p = 0.005, 15.7 days) showed a slower PCO development in comparison to the control (8.6 days). The fibrotic markers f-actin, fibronectin, alpha smooth muscle actin, and collagen type 1 were equally distributed between the two IOLs and differed from the control. Conclusions: A comparable performance has been found in the ex vivo formation of PCO between the two IOLs. Long-term clinical studies are necessary to reach final conclusions.

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“…This was the first study to evaluate the concentration of MMP-2 in the aqueous humor of dogs with cataracts. The decision to investigate MMP-2 was based on previous studies that reported that the latent form of such gelatinase was found to be the most relevant MMP in normal eyes of humans, rabbits, dogs, and chicken (Di Girolamo et al 1996, Weinstein et al 2007, Shimada et al 2014. Although slightly increased concentrations of MMP-2 were observed in dogs with mature cataracts than in controls, significantly higher values were only detected in patients with the hypermature stage of this affection.…”

Section: Discussionmentioning

confidence: 99%

Concentrations of matrix metalloproteinase-2 and interleukin-1 β in the aqueous humor of dogs with normal and cataractous eyes

2020

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We aimed to determine the concentration of MMP-2 and IL-1β in the aqueous humor of dogs with healthy eyes (n=8) and in those with mature (n=8) and hyper mature cataracts (n=8). Correlations between cytokines, cytokines, and intraocular pressure (IOP), as well as cytokines with ages of patients of each group, were also assessed. In patients with cataract, aqueous humor was collected at the end of the electroretinographic procedure. In healthy dogs, aqueous humor was collected before elective surgeries. Cytokine levels were determined using ELISA. IOP was assessed by applanation tonometry. IOP of patients with mature and hyper mature cataracts were lower than the ones measured in normal eyes (P=0.158). MMP-2 aqueous humor concentration was higher in patients with hyper mature cataracts, in comparisons with healthy patients (P=0.04). Average IL-1 β aqueous concentration was higher in patients with cataracts (P<0.0001). Significant higher values of IL-1 β were observed in patients with hyper mature, than in the ones with mature cataracts (P=0.0085). Correlations between MMP-2 and IL-1 β (r=-0.38, P=0.06), MMP-2 and IOP (r=-0.149, P=0.484), and IL-1 β and the ages of patients were not observed (P>0.05). IL-1 β and IOP correlated negatively (r=-0.42, P=0.04). MMP-2 and the ages of patients correlated only in dogs with mature cataracts (r=0.772, P=0.02). It can be concluded that the increment in the aqueous humor concentration of IL-1 β found in dogs with mature and hyper mature cataracts, in addition to the negative relationship of this cytokine with IOP, suggests that IL-1 β is involved in the pathogenesis of LIU. Despite dogs with hypermature cataracts presented significant higher concentrations of MMP-2 in the aqueous humor, such cytokine did not correlate with IL-1 β and IOP. In our study, a relationship between aqueous humor cytokines and the ages of patients was only confirmed between MMP-2 and the ages of dogs with mature cataracts.

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Type I Collagen Accelerates the Spreading of Lens Epithelial Cells through the Expression and Activation of Matrix Metalloproteinases

Abstract: Type I collagen promotes the expression and activation of MMPs in a LEC-specific manner. These results suggest that type I collagen may play a role in PCO development.

Cited by 11 publications

References 57 publications

Laminin α4 overexpression in the anterior lens capsule may contribute to the senescence of human lens epithelial cells in age-related cataract

Laminin α4 overexpression in the anterior lens capsule may contribute to the senescence of human lens epithelial cells in age-related cataract

Evaluation of posterior capsule opacification of the Alcon Clareon IOL vs the Alcon Acrysof IOL using a human capsular bag model

Concentrations of matrix metalloproteinase-2 and interleukin-1 β in the aqueous humor of dogs with normal and cataractous eyes

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