Degeneration and transdifferentiation of human lens epithelial cells in nuclear and anterior polar cataracts

Joo, Choun‐Ki; Lee, Eunjoo H.; Kim, Jong-Chan; Kim, Yeong-Hoon; Lee, Jin-Hak; Kim, Jong-Tak; Chung, Koo–Hyun; Kim, Jin

doi:10.1016/s0886-3350(99)00009-7

Cited by 42 publications

(36 citation statements)

References 17 publications

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“…Many of the markers that are altered in LEC by TGF ␤ are similarly altered in human ASC. Immunohistochemical studies of ASC samples collected at surgery have highlighted the presence of ␣ -smooth muscle actin, vimentin, collagens (types I, III and IV), fi bronectin, tenascin, laminin, and various integrins [Hatae et al, 1993;Schmitt-Graf et al, 1990;Saika et al, 1998;Joo et al, 1999;Lee and Joo, 1999;Zhang et al, 2000;Colitz et al, 2000;Wunderlich et al, 2000;Yoshino et al, 2001;Marcantonio et al, 2003]. Interestingly, the TGF ␤ -inducible gene betaIG-h3 is also upregulated in ASC [Lee et al, 2000].…”

Section: Tgf ␤ -Induced Emt: a Model Of Anterior Subcapsular Cataractmentioning

confidence: 99%

Transforming Growth Factor-β-Induced Epithelial-Mesenchymal Transition in the Lens: A Model for Cataract Formation

Iongh

Wederell²,

Lovicu³

et al. 2005

Cells Tissues Organs

244

228

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The vertebrate lens has a distinct polarity and structure that are regulated by growth factors resident in the ocular media. Fibroblast growth factors, in concert with other growth factors, are key regulators of lens fiber cell differentiation. While members of the transforming growth factor (TGFβ) superfamily have also been implicated to play a role in lens fiber differentiation, inappropriate TGFβ signaling in the anterior lens epithelial cells results in an epithelial-mesenchymal transition (EMT) that bears morphological and molecular resemblance to forms of human cataract, including anterior subcapsular (ASC) and posterior capsule opacification (PCO; also known as secondary cataract or after-cataract), which occurs after cataract surgery. Numerous in vitro and in vivo studies indicate that this TGFβ-induced EMT is part of a wound healing response in lens epithelial cells and is characterized by induced expression of numerous extracellular matrix proteins (laminin, collagens I, III, tenascin, fibronectin, proteoglycans), intermediate filaments (desmin, α-smooth muscle actin) and various integrins (α2, α5, α7B), as well as the loss of epithelial genes [Pax6, Cx43, CP49, α-crystallin, E-cadherin, zonula occludens-1 protein (ZO-1)]. The signaling pathways involved in initiating the EMT seem to primarily involve the Smad-dependent pathway, whereby TGFβ binding to specific high affinity cell surface receptors activates the receptor-Smad/Smad4 complex. Recent studies implicate other factors [such as fibroblast growth factor (FGFs), hepatocyte growth factor, integrins], present in the lens and ocular environment, in the pathogenesis of ASC and PCO. For example, FGF signaling can augment many of the effects of TGFβ, and integrin signaling, possibly via ILK, appears to mediate some of the morphological features of EMT initiated by TGFβ. Increasing attention is now being directed at the network of signaling pathways that effect the EMT in lens epithelial cells, with the aim of identifying potential therapeutic targets to inhibit cataract, particularly PCO, which remains a significant clinical problem in ophthalmology.

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Section: Tgf ␤ -Induced Emt: a Model Of Anterior Subcapsular Cataractmentioning

confidence: 99%

Transforming Growth Factor-β-Induced Epithelial-Mesenchymal Transition in the Lens: A Model for Cataract Formation

Iongh

Wederell²,

Lovicu³

et al. 2005

Cells Tissues Organs

244

228

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“…Morphological studies of the anterior lens capsule and lens epithelium have found different changes in their ultrastructure in age-related nuclear cataracts [10,[17][18][19] . The epithelium can become multilayered [17,19] .…”

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confidence: 99%

“…A mix of both normal and altered epithelial cells is typically observed [11] . The cells can be pleomorphic and degenerated [18,19] , containing pleomorphic nuclei [17] , intracellular vacuoles [9,20,21] and condensed nuclear chromatin [18] . Intercellular spaces can occur between epithelial cells [10,18,22] .…”

mentioning

confidence: 99%

“…The ultrastructure of the anterior lens capsule and lens epithelium is known to be altered in nonuveitic especially white cataracts [10,[17][18][19] . Because intraocular inflammation creates an additional stressor to the crystalline lens [27,28] , we hypothesized that additional ultrastructural changes of the anterior lens capsule and lens epithelium that might occur in uveitic cataracts could explain the unpredictable behavior of the anterior lens capsule that frequently occurs in uveitic cataracts during capsulorhexis.…”

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confidence: 99%

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Ultrastructure of the Anterior Lens Capsule and Epithelium in Cataracts Associated with Uveitis

et al. 2012

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Aims: To study the ultrastructure of the anterior lens capsule and epithelium, and capsular thickness in uveitic cataracts. Methods: Capsulorhexis samples from 20 uveitic cataracts were compared to 20 nuclear cataracts using the semi- and ultra-thin techniques. Results: Extensive epithelial and capsular-epithelial border changes and epithelial-mesenchymal transition in some fibrotic capsules were found only in the uveitic group. All these changes were observed predominately in white uveitic cataracts. Mild and moderate ultrastructural changes were seen in both groups. Surface deposition of amorphous material was also found only in uveitic cataracts. Capsular thickness was not different between the two groups. Conclusions: Uveitic capsules showed more extensive and different ultrastructural changes that probably occurred because of inflammation in the eye and epithelial-mesenchymal transition. These changes might be an additional reason for altered behavior of the lens capsule at capsulorhexis.

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“…We have previously reported that TGF-␤ 1 enhances extracellular matrix production, such as, fibronectin, type I collagen, and the ␣-SMA protein of lens epithelial explants (7). Recent transgenic studies using the dominant negative-TGF-␤ receptor approach have shown that TGF-␤ plays an important role in the normal maturation and survival of lens fiber cells (33).…”

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confidence: 99%

Downregulated Expression of Integrin α6 by Transforming Growth Factor-β1 on Lens Epithelial Cells in Vitro

Lim

Kim

Lee

et al. 2001

Biochemical and Biophysical Research Communications

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Degeneration and transdifferentiation of human lens epithelial cells in nuclear and anterior polar cataracts

Abstract: Lens epithelial cells in different types of cataracts have distinct cellular characteristics and may possess a bipotential nature with the ability to transdifferentiate into mesenchymal cells. This may be an underlying mechanism for the development of cataract and capsule opacification.

Cited by 42 publications

References 17 publications

Transforming Growth Factor-β-Induced Epithelial-Mesenchymal Transition in the Lens: A Model for Cataract Formation

Transforming Growth Factor-β-Induced Epithelial-Mesenchymal Transition in the Lens: A Model for Cataract Formation

Ultrastructure of the Anterior Lens Capsule and Epithelium in Cataracts Associated with Uveitis

Downregulated Expression of Integrin α6 by Transforming Growth Factor-β1 on Lens Epithelial Cells in Vitro

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