Factors modulating mouse lens epithelial cell morphology with differentiation and development of a lentoid structure in vitro

Development ◽  
1987 ◽  
Vol 99 (1) ◽  
pp. 25-32
Author(s):  
A.L. Muggleton-Harris ◽  
N. Higbee

The morphological and cellular changes that occur with differentiation and development of a lentoid structure from cultured mouse lens epithelial cells have been found to be dependent on the presence of lens capsule in association with the cells. The development of the ‘lentoid body’ is a multiphase process involving cell replication, synthesis of mucosubstances and a basement collagen membrane, cell aggregation and differentiation. Stage-specific synthesis of lens proteins confirms that the genes regulating normal differentiation in vivo are operating in the in vitro system. The hydrated collagen gel studies described in this report demonstrate that the cuboidal morphology and apical-basal polarity of the lens epithelial cells are dependent on their relationship with the lens capsule. Following a replicative phase the cells assume a mesenchyme-like morphology and migrate into the gel. Trypsinized cells freed from the lens capsule replicate but form colonies on the surface of the gel. The implications of these results are discussed with respect to previous observations made on normal lens development and the abnormalities associated with the congenital cataractous embryonic lens.

1995 ◽  
Vol 35 ◽  
pp. S199
Author(s):  
J.H. Meyer ◽  
J. Schmidt ◽  
F. Eppinger ◽  
B. Flügel ◽  
K.U. Löffler ◽  
...  

2017 ◽  
Vol 24 (8) ◽  
pp. 1431-1442 ◽  
Author(s):  
Xiaoyun Chen ◽  
Wei Xiao ◽  
Weirong Chen ◽  
Xialin Liu ◽  
Mingxing Wu ◽  
...  

Abstract Fibrosis is a chronic process involving development and progression of multiple diseases in various organs and is responsible for almost half of all known deaths. Epithelial–mesenchymal transition (EMT) is the vital process in organ fibrosis. Lens is an elegant biological tool to investigate the fibrosis process because of its unique biological properties. Using gain- and loss-of-function assays, and different lens fibrosis models, here we demonstrated that microRNA (miR)-26a and miR-26b, members of the miR-26 family have key roles in EMT and fibrosis. They can significantly inhibit proliferation, migration, EMT of lens epithelial cells and lens fibrosis in vitro and in vivo. Interestingly, we revealed that the mechanisms of anti-EMT effects of miR-26a and -26b are via directly targeting Jagged-1 and suppressing Jagged-1/Notch signaling. Furthermore, we provided in vitro and in vivo evidence that Jagged-1/Notch signaling is activated in TGFβ2-stimulated EMT, and blockade of Notch signaling can reverse lens epithelial cells (LECs) EMT and lens fibrosis. Given the general involvement of EMT in most fibrotic diseases, cancer metastasis and recurrence, miR-26 family and Notch pathway may have therapeutic uses in treating fibrotic diseases and cancers.


1982 ◽  
Vol 95 (1) ◽  
pp. 333-339 ◽  
Author(s):  
G Greenburg ◽  
E D Hay

This study of epithelial-mesenchymal transformation and epithelial cell polarity in vitro reveals that environmental conditions can have a profound effect on the epithelial phenotype, cell shape, and polarity as expressed by the presence of apical and basal surfaces. A number of different adult and embryonic epithelia were suspended within native collagen gels. Under these conditions, cells elongate, detach from the explants, and migrate as individual cells within the three-dimensional lattice, a previously unknown property of well-differentiated epithelia. Epithelial cells from adult and embryonic anterior lens were studied in detail. Elongated cells derived from the apical surface develop pseudopodia and filopodia characteristic of migratory cells and acquire a morphology and ultrastructure virtually indistinguishable from that of mesenchymal cells in vivo. It is concluded from these experiments that the three-dimensional collagen gel can promote dissociation, migration, and acquisition of secretory organelles by differentiated epithelial cells, and can abolish the apical-basal cell polarity characteristic of the original epithelium.


1998 ◽  
Vol 140 (1) ◽  
pp. 153-158 ◽  
Author(s):  
Yasuki Ishizaki ◽  
Michael D. Jacobson ◽  
Martin C. Raff

There is increasing evidence that programmed cell death (PCD) depends on a novel family of intracellular cysteine proteases, called caspases, that includes the Ced-3 protease in the nematode Caenorhabditis elegans and the interleukin-1β–converting enzyme (ICE)-like proteases in mammals. Some developing cells, including lens epithelial cells, erythroblasts, and keratinocytes, lose their nucleus and other organelles when they terminally differentiate, but it is not known whether the enzymatic machinery of PCD is involved in any of these normal differentiation events. We show here that at least one CPP32 (caspase-3)-like member of the caspase family becomes activated when rodent lens epithelial cells terminally differentiate into anucleate lens fibers in vivo, and that a peptide inhibitor of these proteases blocks the denucleation process in an in vitro model of lens fiber differentiation. These findings suggest that at least part of the machinery of PCD is involved in lens fiber differentiation.


2021 ◽  
Author(s):  
Brian Thompson ◽  
Emily A Davidson ◽  
Ying Chen ◽  
David J Orlicky ◽  
David C Thompson ◽  
...  

Recent reports have challenged the notion that the lens is immune-privileged. However, these studies have not fully identified the molecular mechanism(s) that promote immune surveillance of the lens. Using a mouse model of targeted glutathione (GSH) deficiency in ocular surface tissues, we have investigated the role of oxidative stress in upregulating cytokine expression and promoting immune surveillance of the eye. RNA-sequencing of lenses from postnatal day (P) 1-aged Gclcf/f;Le-CreTg/- (KO) and Gclcf/f;Le-Cre-/- control (CON) mice revealed upregulation of many cytokines (e.g., CCL4, GDF15, CSF1) and immune response genes in the lenses of KO mice. The eyes of KO mice had a greater number of cells in the aqueous and vitreous humors at P1, P20 and P50 than age-matched CON and Gclcw/w;Le-CreTg/- (CRE) mice. Histological analyses revealed the presence of innate immune cells (i.e., macrophages, leukocytes) in ocular structures of the KO mice. At P20, the expression of cytokines and ROS content was higher in the lenses of KO mice than in those from age-matched CRE and CON mice, suggesting that oxidative stress may induce cytokine expression. In vitro administration of the oxidant, hydrogen peroxide, and the depletion of GSH (using buthionine sulfoximine (BSO)) in 21EM15 lens epithelial cells induced cytokine expression, an effect that was prevented by co-treatment of the cells with N-acetyl-L-cysteine (NAC), a antioxidant. The in vivo and ex vivo induction of cytokine expression by oxidative stress was associated with the expression of markers of epithelial-to-mesenchymal transition (EMT), α-SMA, in lens cells. Given that EMT of lens epithelial cells causes posterior capsule opacification (PCO), we propose that oxidative stress induces cytokine expression, EMT and the development of PCO in a positive feedback loop. Collectively these data indicate that oxidative stress induces inflammation of lens cells which promotes immune surveillance of ocular structures.


1999 ◽  
Vol 5 (S2) ◽  
pp. 1080-1081
Author(s):  
J. Potts ◽  
P. Conley ◽  
R. Champion

The embryonic lens contains two populations of cells, lens epithelial cells and lens fiber cells. As the growth of the human lens is linear from the age of 10 to 90, lens epithelial cells divide and differentiate into fiber cells at a uniform rate during adulthood. Any defects that arise during fiber formation will remain in the lens. We postulate that regulation of early lens growth is critical for the onset of cataracts that usually occur later in life. Slowing the growth of the lens could therefore provide a strategy to suppress the formation of cataracts. However, the factor(s) that control lens growth in vivo have not been identified.We have identified 18 receptor and cytoplasmic kinases present in lens epithelial cells. Using these as potential targets for factors controlling growth, we tested corresponding ligands in a lens epithelial cell proliferation assay. Platelet-derived growth factor (PDGF) proved to promote a growth activity similar to, but distinct from, that of embryo serum.


1981 ◽  
Vol 32 (5) ◽  
pp. 563-573 ◽  
Author(s):  
A.L. Muggleton-Harris ◽  
R.D. Lipman ◽  
J. Kearns

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