Lens Stretching Modulates Lens Epithelial Cell Proliferation via YAP Regulation

Kumar, Bharat; Chandler, Heather L.; Plageman, Timothy F.; Reilly, Matthew A.

doi:10.1167/iovs.19-26893

Cited by 31 publications

(23 citation statements)

References 63 publications

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“…121,122 Additionally, simulating accommodative forces in whole porcine lens cultures in vitro has been found to induce mitotic activity in the lens epithelium. 123 posterior capsule and PCO. 124,125 Cataract surgery is known to alter LEC proliferation and disrupt both the biochemical and biomechanical homeostasis of the lens.…”

Section: Lec Mediated Lens Regenerationmentioning

confidence: 99%

The Development, Growth, and Regeneration of the Crystalline Lens: A Review

Kumar

Reilly

2019

Current Eye Research

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Purpose: This review aims to provide an understanding of the history of research on, the biological processes governing the different forms of, and an overview of more recent work on lens regeneration as they will likely prove vital in bringing the study of lens regeneration into the clinic. Methods: A review of the literature on lens regeneration research was conducted. Results: Lens regeneration is characterized by the regrowth or repair of the lens following the removal of either a portion or of the entire lens. A brief history of research on lens regeneration is provided, from the discovery in early antiquity of the ability of some animals to regenerate lost tissue, to the systematic cataloguing of the mechanisms of lens regeneration in the 19th century, until the more modern unraveling of the genetic and biochemical processes governing lens regeneration. The anatomy and physiology of the lens as well as the mechanisms by which the lens develops inform its regenerative capabilities by determining the processes that must occur in order to regrow a new lens or repair a damaged one. Lens regeneration occurs by one of several species-dependent methods: some amphibians can regrow a new lens after complete removal of the old one while some mammals can only repair a damaged lens. This review provides an overview of the mechanisms controlling the different types of lens regeneration. Conclusion: The development and growth of the intact lens influence the mechanisms that govern lens regeneration. Recent advances in the field have begun to apply concepts of the field in the clinic and have made significant progress towards realizing the goal of using lens regeneration to repair a damaged lens in the clinic.

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Section: Lec Mediated Lens Regenerationmentioning

confidence: 99%

The Development, Growth, and Regeneration of the Crystalline Lens: A Review

Kumar

Reilly

2019

Current Eye Research

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“…Additionally, whole tissue culture of lenses has allowed for the emergence of lens mechanobiology. We demonstrated how tissue-scale mechanical loads are transmitted onto lens epithelial cells [15 , 16] ; moreover, others have demonstrated that whole lens stretch results in lens epithelial cell proliferation [16] . Furthermore, the ex vivo culture system has allowed for the study of lens EMT [4 , 5 , 7 , [17] , [18] , [19] .…”

Section: Methods Detailsmentioning

confidence: 80%

“…The ex vivo culture of intact, isolated lenses is a powerful method to study lens epithelial cell biology and pathology [7 , 15 , 16] . As compared to two-dimensional culture of lens epithelial derived cells or cell lines, whole lens culture allows for preservation of lens/cellular structures.…”

Section: Methods Detailsmentioning

confidence: 99%

Whole mount staining of lenses for visualization of lens epithelial cell proteins

et al. 2021

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Whole mount imaging of the lens allows for high spatial resolution visualization of lens epithelial structures by using small molecule fluorescent probes. However, the visualization of specific proteins in lens epithelial cells within whole lenses remains a challenge as the capsule that surrounds the lens does not allow penetration of antibodies. Here we describe a whole mount imaging method that allows us to overcome this challenge by digesting the lens capsules of paraformaldehyde fixed lenses using collagenase. This method enables the penetration of antibodies for effective visualization of proteins in the epithelium of whole lenses. A limitation to lens whole mount imaging is the ability to visualize specific proteins as the collagen capsule surrounding the lens impedes the penetration of antibodies This protocol helps overcome this limitation by a light collagenase digestion of the capsule of fixed lenses prior to immunostaining This method allows for the imaging of specific proteins in the epithelium of the whole lens tissue

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“…A recent paper showed the feasibility of culturing whole lenses in vitro, which might solve the problems of nonbiological substrate and the lack of lens capsule for lens cells. 76 Future studies will build on these findings by using whole lens culture models, quantifying intercellular levels of the antioxidants, evaluating the effects of these antioxidants on endogenous cellularly produced ROS levels, and quantifying the concentrations of the reduced and oxidized forms of vitamin C and glutathione in a hypoxic environment that better mimics in vivo conditions. A limitation of this study was measurement of ROS using a DCF assay rather than hydrogen peroxide directly.…”

Section: Figure 5 Glutathione Prolonged the Antioxidant Activity Of Vitamin C Up To 3 Days After Incubationmentioning

confidence: 99%

Glutathione Improves the Antioxidant Activity of Vitamin C in Human Lens and Retinal Epithelial Cells: Implications for Vitreous Substitutes

Tram

McLean

Swindle-Reilly

2020

Current Eye Research

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Purpose: Tissues in the eye are particularly susceptible to oxidative damage due to light exposure. While vitamin C (ascorbic acid) has been noted as a vital antioxidant in the vitreous humor, its physiological concentration (1-2 mM) has been shown to be toxic to retinal and lens epithelial cells in in vitro cell culture. We have explored adding vitamin C to hydrogel vitreous substitutes as a potential therapeutic to prevent oxidative damage to intraocular tissues after vitrectomy. However, vitamin C degrades rapidly even when loaded at high concentrations, limiting its long-term effectiveness. Glutathione, another antioxidant found abundantly in the lens at concentrations of 2-10 mM, was proposed to be used in conjunction with vitamin C. Methods: Cell viability and reactive oxygen species activity of human retinal and lens epithelial cells treated with various combinations of vitamin C, glutathione, hydrogen peroxide, and a hydrogel vitreous substitute were determined using CellTiter-Glo luminescent cell viability assay and dichlorofluorescein assay, respectively. The vitamin C remaining in hydrogel vitreous substitute or glutathione-vitamin C solutions was determined using a microplate reader at 265 nm wavelength, compared against standard solutions with known concentrations. Results: Glutathione protected the lens and retinal cells from the negative effect of vitamin C on cell viability and prolonged the antioxidant effect of vitamin C in vitro. While the detected reading of pure vitamin C solution decreased rapidly from 100% to 10% by 3 days, glutathione provided a significant extension to vitamin C stability, with 70% remaining after 14 days when the glutathione was used at physiological concentrations found in the lens (2-10 mM). Conclusions: These results indicate glutathione might be an effective addition to vitamin C in intraocular implants, including potential vitreous substitutes, and warrants additional studies on the effectiveness of the vitamin C -glutathione combination in preventing oxidative stress post-vitrectomy.

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Lens Stretching Modulates Lens Epithelial Cell Proliferation via YAP Regulation

Cited by 31 publications

References 63 publications

The Development, Growth, and Regeneration of the Crystalline Lens: A Review

The Development, Growth, and Regeneration of the Crystalline Lens: A Review

Whole mount staining of lenses for visualization of lens epithelial cell proteins

Glutathione Improves the Antioxidant Activity of Vitamin C in Human Lens and Retinal Epithelial Cells: Implications for Vitreous Substitutes

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