This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lovicu, F. J Articles by McAvoy, J. W Search for Related Content PubMed PubMed Citation Articles by Lovicu, F. J Articles by McAvoy, J. W

TGFß induces morphological and molecular changes similar to human anterior subcapsular cataract

¹ Department of Anatomy and Histology and Institute for Biomedical Research, University of Sydney, NSW, Australia
² Save Sight Institute and Department of Clinical Ophthalmology and Eye Health, University of Sydney, NSW, Australia
³ Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

Correspondence to:
Correspondence to:
Frank J Lovicu, Save Sight Institute and Department of Clinical Ophthalmology and Eye Health, University of Sydney, NSW, Australia;
lovicu{at}anatomy.usyd.edu.au

Background: Transforming growth factor ß (TGFß) has been shown to induce subcapsular plaques in cultured rat lenses as well as in lenses of transgenic mice. In the present study the authors have extended their analysis of these cataract models to determine how closely they mimic human cataract. In particular, they studied the maturation of cataract in the transgenic model to determine if it develops similar features as previously described for anterior subcapsular cataract (ASC) in humans. Furthermore, they investigated whether both of these animal models express the range of molecular markers that have now been shown to be present in human ASC.

Methods: Histology and periodic acid Schiff staining were used to study the development and maturation of subcapsular plaques in transgenic mice overexpressing TGFß1 in the lens. Immunolabelling methods were used to identify the molecular markers for ASC in both the transgenic mouse model and in rat lenses cultured with TGFß2.

Results: Histological analysis showed that the subcapsular plaques that develop in adult transgenic mouse lenses bear a striking similarity to mature human ASC, including the formation of a new epithelial-like layer extending between the subcapsular plaque and the underlying fibre mass. All known molecular markers for human ASC were induced in both rodent models, including collagen types I and III, tenascin, and fibronectin. They also identified the presence of desmin in these plaques, a putative novel marker for human cataract.

Conclusions: In both transgenic mouse and rat lens culture models TGFß induces markers similar to those found in human ASC. Atypical expression of these cataract markers is also characteristic of posterior capsular opacification (PCO). The molecular markers expressed are typical of a myofibroblastic/fibroblastic phenotype and suggest that a common feature of ASC and PCO may be induction of an epithelial-mesenchymal transition by TGFß.

Keywords: TGFß; anterior subcapsular cataract; rats; mice

Abbreviations: ASC, anterior subcapsular cataract; ECM, extracellular matrix; EMT, epithelial mesenchymal transition; PBS, phosphate buffered saline; PCO, posterior capsular opacification; TGFß, transforming growth factor ß

This article has been cited by other articles:

				N. Awasthi, S. T. Wang-Su, and B. J. Wagner Downregulation of MMP-2 and -9 by Proteasome Inhibition: A Possible Mechanism to Decrease LEC Migration and Prevent Posterior Capsular Opacification Invest. Ophthalmol. Vis. Sci., May 1, 2008; 49(5): 1998 - 2003. [Abstract] [Full Text] [PDF]

				J. Choi, S. Y. Park, and C.-K. Joo Transforming Growth Factor-{beta}1 Represses E-Cadherin Production via Slug Expression in Lens Epithelial Cells Invest. Ophthalmol. Vis. Sci., June 1, 2007; 48(6): 2708 - 2718. [Abstract] [Full Text] [PDF]

				V. N. Simirskii, R. S. Lee, E. F. Wawrousek, and M. K. Duncan Inbred FVB/N Mice Are Mutant at the cp49/Bfsp2 Locus and Lack Beaded Filament Proteins in the Lens Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4931 - 4934. [Abstract] [Full Text] [PDF]

				A. Banh, P. A. Deschamps, J. Gauldie, P. A. Overbeek, J. G. Sivak, and J. A. West-Mays Lens-Specific Expression of TGF-{beta} Induces Anterior Subcapsular Cataract Formation in the Absence of Smad3. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3450 - 3460. [Abstract] [Full Text] [PDF]

				M. R. Hosler, S.-T. Wang-Su, and B. J. Wagner Role of the Proteasome in TGF-{beta} Signaling in Lens Epithelial Cells Invest. Ophthalmol. Vis. Sci., May 1, 2006; 47(5): 2045 - 2052. [Abstract] [Full Text] [PDF]

				D. J. Dwivedi, G. Pino, A. Banh, Z. Nathu, D. Howchin, P. Margetts, J. G. Sivak, and J. A. West-Mays Matrix Metalloproteinase Inhibitors Suppress Transforming Growth Factor-{beta}-Induced Subcapsular Cataract Formation Am. J. Pathol., January 1, 2006; 168(1): 69 - 79. [Abstract] [Full Text] [PDF]

				N. Lois, J. Taylor, A. D. McKinnon, G. C. Smith, R. van't Hof, and J. V. Forrester Effect of TGF-{beta}2 and Anti-TGF-{beta}2 Antibody in a New In Vivo Rodent Model of Posterior Capsule Opacification Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4260 - 4266. [Abstract] [Full Text] [PDF]

				A. J. Zandy, S. Lakhani, T. Zheng, R. A. Flavell, and S. Bassnett Role of the Executioner Caspases during Lens Development J. Biol. Chem., August 26, 2005; 280(34): 30263 - 30272. [Abstract] [Full Text] [PDF]

				F. J. Lovicu, P. Steven, S. Saika, and J. W. McAvoy Aberrant Lens Fiber Differentiation in Anterior Subcapsular Cataract Formation: A Process Dependent on Reduced Levels of Pax6 Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 1946 - 1953. [Abstract] [Full Text] [PDF]

				M. Der Perng, S. F. Wen, P. van den IJssel, A. R. Prescott, and R. A. Quinlan Desmin Aggregate Formation by R120G {alpha}B-Crystallin Is Caused by Altered Filament Interactions and Is Dependent upon Network Status in Cells Mol. Biol. Cell, May 1, 2004; 15(5): 2335 - 2346. [Abstract] [Full Text] [PDF]

				N. Kaminski, J. A. Belperio, P. B. Bitterman, L. Chen, S. W. Chensue, A. M.K. Choi, S. Dacic, J. H. Dauber, R. M. du Bois, J. J. Enghild, et al. Idiopathic Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., September 1, 2003; 29(3): S1 - 105. [Full Text] [PDF]

				N. Lois, R. Dawson, A. D. McKinnon, and J. V. Forrester A New Model of Posterior Capsule Opacification in Rodents Invest. Ophthalmol. Vis. Sci., August 1, 2003; 44(8): 3450 - 3457. [Abstract] [Full Text] [PDF]

				S. Saika, T. Miyamoto, I. Ishida, Y. Ohnishi, and A. Ooshima Osteopontin: A Component of Matrix in Capsular Opacification and Subcapsular Cataract Invest. Ophthalmol. Vis. Sci., April 1, 2003; 44(4): 1622 - 1628. [Abstract] [Full Text] [PDF]