Separation of Fibres from the Capsule Enhances Mitotic Activity of Human Lens Epithelium

Rakic, Jean-Marie; Galand, A; Vrensen, Gijs F.J.M.

doi:10.1006/exer.1996.0179

Cited by 58 publications

(41 citation statements)

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“…Some studies suggest that this lack of hyperproliferation of ␣BϪ/Ϫ cells is a result of the negative effect exerted by lens fibers on mitotic activity of lens epithelial cells (71). It remains to be determined whether the expression of p53 is enhanced in the ␣BϪ/Ϫ mouse lens epithelium in vivo.…”

Section: Discussionmentioning

confidence: 99%

Hyperproliferation and p53 Status of Lens Epithelial Cells Derived from αB-crystallin Knockout Mice

Bai

Wawrousek

et al. 2003

Journal of Biological Chemistry

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␣B-Crystallin, a major protein of lens fiber cells, is a stress-induced chaperone expressed at low levels in the lens epithelium and numerous other tissues, and its expression is enhanced in certain pathological conditions. However, the function of ␣B in these tissues is not known. Lenses of ␣B؊/؊ mice develop degeneration of specific skeletal muscles but do not develop cataracts. Recent work in our laboratory indicates that primary cultures of ␣B؊/؊ lens epithelial cells demonstrate genomic instability and undergo hyperproliferation at a frequency 4 orders of magnitude greater than that predicted by spontaneous immortalization of rodent cells. We now demonstrate that the hyperproliferative ␣B؊/؊ lens epithelial cells undergo phenotypic changes that include the appearance of the p53 protein as shown by immunoblot analysis. Sequence analysis showed a lack of mutations in the p53 coding region of hyperproliferative ␣B؊/؊ cells. However, the reentry of hyperproliferative ␣B؊/؊ cells into S phase and mitosis after DNA damage by ␥-irradiation were consistent with impaired p53 checkpoint function in these cells. The results demonstrate that expression of functionally impaired p53 is one of the factors that promote immortalization of lens epithelial cells derived from ␣B؊/؊ mice. Fluorescence in situ hybridization using probes prepared from centromere-specific mouse P1 clones of chromosomes 1 and 9 demonstrated that the hyperproliferative ␣B؊/؊ cells were 30% diploid and 70% tetraploid, whereas wild type cells were 83% diploid. Further evidence of genomic instability was obtained when the hyperproliferative ␣B؊/؊ cells were labeled with anti-␤-tubulin antibodies. Examination of the hyperproliferative ␣B؊/؊ mitotic profiles revealed the presence of cells that failed to round up for mitosis, or arrested in cytokinesis, and binucleated cells in which nuclear division had occurred without cell division. These results suggest that the stress protein and molecular chaperone ␣B-crystallin protects cells from acquiring impaired p53 protein and genomic instability.␣〉-crystallin (␣B) 1 is a stress-inducible chaperone expressed in lens fiber cells and in the lens epithelium. It has also been detected at varying levels in numerous tissues, particularly heart, kidney, skeletal muscle, lung, and brain (1-3). However, the function of ␣B in these tissues remains elusive. A number of recent studies suggest a broad cellular function of ␣B associated with growth (4 -13). ␣A-and ␣B-crystallins have autokinase activity (4). ␣B expression increases in mitotically arrested NIH 3T3 fibroblasts, and in Chinese hamster ovary cells induced to express ␣B, the localization of ␣B changes from the cytoplasm to nucleus during interphase (5, 6). Nearly 20% of ␣B polypeptides isolated from the lens are phosphorylated in vivo, suggesting an association with signal transduction pathways (8, 12). Phosphorylated forms of ␣B have been detected in the centrosomes and midbodies of dividing cells (7). ␣B also accumulates in the developing central nervous syste...

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Section: Discussionmentioning

confidence: 99%

Hyperproliferation and p53 Status of Lens Epithelial Cells Derived from αB-crystallin Knockout Mice

Bai

Wawrousek

et al. 2003

Journal of Biological Chemistry

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“…Cell division is also absent in the transitional zone just anterior to the meridional rows (Rafferty and Rafferty, 1981). Growth and survival factors that influence cell division in the lens have been extensively studied (Reddan, 1982;McAvoy and Chamberlain, 1989;Hyatt and Beebe, 1993;Ishizaki et al, 1993;Zelenka et al, 1997;Rakic et al, 1997;Singh et al, 2000). However, regulation of cell division in the lens is not fully understood.…”

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confidence: 99%

Reduced survival of lens epithelial cells in theαA-crystallin-knockout mouse

Bai

Andley

2003

Journal of Cell Science

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αA-Crystallin (αA) is a molecular chaperone expressed preferentially in the lens. αA transcripts are first detected during the early stages of lens development and its synthesis continues as the lens grows throughout life. αA–/– mouse lenses are smaller than controls, and lens epithelial cells derived from these mice have diminished growth in culture. In the current work, we tested the hypothesis thatαA prevents cell death at a specific stage of the cell cycle in vivo. Seven-day-old 129Sv (wild-type) and αA–/–mice were injected with 5-bromo-2′-deoxyuridine (BrdU) to label newly synthesized DNA in proliferating cells. To follow the fate of the labeled cells, wholemounts of the capsule epithelial explants were made at successive times after the BrdU pulse, and the labeling index was determined. Immunofluorescence and confocal microscopy showed that both wild-type andαA–/– cells had a 3-hour labeling index of 4.5%in the central region of the wholemount, indicating that the number of cells in S phase was the same. Twenty-four hours after the pulse, individual cells labeled with BrdU had divided and BrdU-labeled cells were detected in pairs. The 24-hour labeling index in the wild-type lens was 8.6%, but in theαA–/– lens it was significantly lower, suggesting that some of the cells failed to divide and/or that the daughter cells died during mitosis. TUNEL labeling was rarely detected in the wild-type lens, but was significant and always detected in pairs in theαA–/– wholemounts. Dual labeling with TUNEL and BrdU also suggested that the labeled cells were dying in pairs in theαA–/– lens epithelium. Immunolabeling of wholemounts with β-tubulin antibodies indicated that the anaphase spindle in a significant proportion of αA–/– cells was not well organized. Examination of the cellular distribution of αA in cultured lens epithelial cells showed that it was concentrated in the intercellular microtubules of cells undergoing cytokinesis. These data suggest that αA expression in vivo protects against cell death during mitosis in the lens epithelium, and the smaller size of theαA–/– lens may be due to a decrease in the net production of epithelial cells.

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“…Ob motnjah se te celice začnejo razmnože-vati in zagotavljajo delitev, ki bo oskrbela osrednjo in germinativno območje s celicami, ki imajo zmogljivost nadaljnjih delitev. Interakcija apikalnih površin leč-nih epitelnih celic, ki so obrnjene navznoter proti jedru, z notranjim delom leče, kjer se dotikajo apikalne površine lamelnih celic, uravnava razmnoževanje lečnih epitelnih celic (24,25). BMI-1, protein, ki je pri človeku kodiran z genom BMI-1 (B-celični specifični virus mišje levkemije), je potreben za vzdrževanje in obnovo endogenih lečnih epitelnih celic.…”

Section: Preprečevanje Oziroma Spodbujanje Rasti Lečnih Epitelnih Celicunclassified

Vloga lečnih epitelnih celic pri razvoju zamotnitve zadnje lečne ovojnice in pri obnovi leče po operaciji prirojene sive mrene

Andjelić¹

2017

SlovMedJour

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Vloga lečnih epitelnih celic pri razvoju zamotnitve zadnje lečne ovojnice in pri obnovi leče po operaciji prirojene sive mreneThe role of lens epithelial cells in the development of the posterior capsule opacification and in the lens regeneration after congenital cataract surgery Sofija andjelic IzvlečekNajpogostejši zaplet po operaciji sive mrene je zamotnitev zadnje lečne ovojnice (angl. posterior capsule opacification, PCO), ki pogosto povzroči poslabšanje vidne funkcije. Vzrok za nastanek PCO je razmnoževanje in selitev lečnih epitelnih celic, ki se med operacijo ne uspejo odstraniti in ostanejo na lečni ovojnici. PCO ima značilnost fibroze, ki se kaže z intenzivnejšim deljenjem, selitvijo, odlaganjem matriksa in spremembo oziroma prehodom v miofibroblaste.Presenetljivo rezultati najnovejših raziskav kažejo, da so lečne epitelne celice pomembne pri obnovi oz. regeneraciji leče pri novem načinu operacije prirojene sive mrene. Pri tem načinu se odstrani le 1-1,5 mm lečne ovojnice bolj lateralno, tako da ostane večji del lečnega epitela nepoškodovan. Nov način operacije se razlikuje od sedanjega, saj se pri njem ohranijo endogene lečne epitelne celice, ki se ne poskušajo odstraniti oz. uničiti. Lečne epitelne celice se tako lahko po operaciji razmnožujejo znotraj lečne ovojnice. Uspeli so doseči funkcionalno obnovo leče pri kuncih in opicah pa tudi pri otrocih s prirojeno očesno mreno. Za obnovo očesne leče je ključnega pomena pluripotentnost leč-nih epitelnih celic, ki imajo naravo zarodnih celic.Ex vivo kulture eksplantov lečnih ovojnic, na katerih so lečne epitelne celice, lahko uporabljamo za testiranje farmakoloških reagentov, s katerimi spodbujamo ali zaviramo rast lečnih epitelnih celic. Funkcionalnost celic in odgovore na farmakološke reagente lahko ovrednotimo z analizo znotraj-in zunajcelične signalizacije kalcija (Ca 2+ ).Spodbujanje rasti lečnih epitelnih celic je pomembno pri obnovi leče pri novem načinu operacije prirojene sive mrene, nasprotno pa je zaviranje rasti lečnih epitelnih celic pomembno pri prepreče-vanju razvoja PCO. Članek opisuje metode analize delovanja lečnih epitelnih celic, ki jih pridobimo pri operacijah sive mrene ter jih izvajamo v laboratoriju na Očesni kliniki UKC v Ljubljani. AbstractPosterior capsule opacification-PCO is the most common complication after cataract surgery. Proliferation and migration of lens epithelial cells that remain in the capsular bag following cataract surgery can lead to the development of PCO, which is the main cause of deterioration of visual function. PCO shows the classic features of fibrosis, including hyperproliferation, migration, deposition of matrix and its shrinkage and transdifferentiation into myofibroblast. Astonishingly, the results of recent research show the importance of lens epithelium for lens regeneration following congenital cataract surgery. New minimally invasive cataract surgery removes only 1-1.5 mm of lens epithelium more laterally, so the major part of the epithelium remains in the

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Separation of Fibres from the Capsule Enhances Mitotic Activity of Human Lens Epithelium

Cited by 58 publications

References 0 publications

Hyperproliferation and p53 Status of Lens Epithelial Cells Derived from αB-crystallin Knockout Mice

Hyperproliferation and p53 Status of Lens Epithelial Cells Derived from αB-crystallin Knockout Mice

Reduced survival of lens epithelial cells in theαA-crystallin-knockout mouse

Vloga lečnih epitelnih celic pri razvoju zamotnitve zadnje lečne ovojnice in pri obnovi leče po operaciji prirojene sive mrene

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