Immunocytochemistry of types I-IV collagen in human anterior subcapsular cataracts

Hatae, Tanenori; Ishibashi, Tatsuro; Yoshitomi, Fumiaki; Shibata, Yosaburo

doi:10.1007/bf00936523

Cited by 52 publications

(23 citation statements)

References 8 publications

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“…The former group of cells existed in multi-layer and revealed structureless deposits of high density among the cells, which confirmed the findings from previous studies [3][4][5][6]. We also noted phagocytosis in some of these LECs, which may support the results reported by Yajima [5].…”

Section: Discussionsupporting

confidence: 82%

Histopathological and Cell Biological Analyses of the Formation Mechanism of Anterior Polar Cataract

Majima

Majima²

1998

Ophthalmologica

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Anterior polar cataract, defined as an opacification limited to the anterior polar region of the crystalline lens, results in a significant decline of vision even though the area of opacification is generally small. Having performed histopathological and cell biological studies in an attempt to identify the formation mechanism of anterior polar cataract, we found that lens epithelial cells (LECs) in contact with the opacified region were arranged in a monolayer and contained vacuoles. Furthermore, compared to LECs obtained from cortical and nuclear cataractous lenses and cultured for the study, these LECs revealed a significantly diminished proliferation, suggesting that their physiological activity had been reduced. On the other hand, LECs existing within the opacified region were multi-layered, and there were structureless deposits including remnants of organelles among the cells. Based on these findings, we have concluded that the formation mechanism of anterior polar cataract is as follows: LECs contacting the opacified region initially undergo significant mitosis; rather than migrating towards the equator, these proliferating cells accumulate and form a multilayer in the anterior polar region. Since multi-layered cells are surrounded by the anterior lens capsule and the lens cortex, there is a limit as to how many layers the cells can continue to form; when this limit is reached, these cells next undergo endocytosis and exocytosis. Because the physiological activity has been reduced as a result of having undergone significant proliferation, the cells contacting the opacified area are no longer able to force the proliferating cells towards the anterior polar region; hence multi-layering of the cells and the entire cellular movement are terminated at this point and result in cells with vacuoles and diminished physiological activity. While further studies are required to confirm our hypothesis, we believe this is the first study to suggest a possible mechanism of formation of anterior polar cataract.

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Section: Discussionsupporting

confidence: 82%

Histopathological and Cell Biological Analyses of the Formation Mechanism of Anterior Polar Cataract

Majima

Majima²

1998

Ophthalmologica

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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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“…This result is supported by Ibaraki's [15] report. As multilayered LECs consisting of fibroblastlike cells are observed in clinical cases with anterior polar cataract and secondary cataract as a fibrous opacification of the anterior lens capsule following intraocular lens (IOL) implantation [16,17], I thought that EGF not only induced the differentiation of LECs but was also the cause of opacification of the anterior polar cataractous lens and of the fibrous opacification of the anterior lens capsule following IOL.…”

Section: Discussionmentioning

confidence: 99%

Effect of Epidermal Growth Factor upon Morphological Changes of Human Lens Epithelial Cells

Majima

1998

Ophthalmologica

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Phase-contrast and transmission electron microscopic studies were performed to evaluate the effect of epidermal growth factor (EGF) upon the morphology of lens epithelial cells (LECs) obtained from human cataractous lenses, cultured on human anterior lens capsules, and divided into the following three groups: group 1 receiving no EGF supplement, group 2 supplemented with 1 ng/ml EGF, and group 3 supplemented with 10 ng/ml EGF. Phase-contrast microscopy revealed that the cells in the group supplemented with 1 ng/ml EGF concentration had elogated, and those supplemented with 10 ng/ml EGF disclosed changes indicating fibroblast-like cells. Under transmission electron microscopy, the cells in the group supplemented with 1 ng/ml EGF concentration had become multilayered and a few cells had a ball-and-socket junction structure and nucleolar chromatin condensation, while those supplemented with 10 ng/ml EGF showed changes not only in the cells but also in the anterior lens capsules to present numerous microfibers. This is the first study to confirm the effect of EGF upon LECs cultured on anterior lens capsules, a condition closely resembling the intraocular environment, and these findings are significant.

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Immunocytochemistry of types I-IV collagen in human anterior subcapsular cataracts

Cited by 52 publications

References 8 publications

Histopathological and Cell Biological Analyses of the Formation Mechanism of Anterior Polar Cataract

Histopathological and Cell Biological Analyses of the Formation Mechanism of Anterior Polar Cataract

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

Effect of Epidermal Growth Factor upon Morphological Changes of Human Lens Epithelial Cells

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