Deregulation of lens epithelial cell proliferation and differentiation during the development of TGFbeta-induced anterior subcapsular cataract.
Normal lens development and growth is dependent on the tight spatial and temporal regulation of lens cell proliferation and fiber cell differentiation. The present study reports that these same cellular processes contribute to lens pathology as they become deregulated in the process of anterior subcapsular cataract development in a transgenic mouse model. During the formation and growth of transforming growth factor (TGF)beta-induced subcapsular plaques, lens epithelial cells lose key phenotypic markers including E-cadherin and connexin 43, they multilayer and subsequently differentiate into myofibroblastic and/or fiber-like cells. Growth of the subcapsular plaques in the transgenic mouse is sustained by an ordered process of cell proliferation, exit from the cell cycle and differentiation. As reiterating ordered growth and differentiation patterns is atypical of the direct effects of TGFbeta on lens cells in vitro, we propose that other growth factors in the eye, namely fibroblast growth factor, may also play a role in the establishment and regulation of the key cellular processes leading to lens pathology. Obtaining a better understanding of the molecular aspects and cellular dynamics of cataract formation and growth is central to devising strategies for slowing or preventing this disease.
Lovicu
F J
FJ
Save Sight Institute, University of Sydney, Australia. lovicu@anatomy.usyd.edu.au
Ang
S
S
Chorazyczewska
M
M
McAvoy
J W
JW
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D015820:Cadherins / Q000378:metabolism; D002386:Cataract / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D018031:Connexin 43 / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D007908:Lens, Crystalline / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D015415:Biomarkers; D015820:Cadherins; C493965:Cdkn1c protein, mouse; D018797:Cell Cycle Proteins; D018031:Connexin 43; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors