TGFbeta induces morphological and molecular changes similar to human anterior subcapsular cataract.
BACKGROUND
Transforming growth factor beta (TGFbeta) 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 TGFbeta1 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 TGFbeta2.


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 TGFbeta 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 TGFbeta.
Lovicu
Frank J
FJ
Department of Anatomy and Histology and Institute for Biomedical Research, University of Sydney, NSW, Australia. lovicu@anatomy.usyd.edu.au
Schulz
Mark W
MW
Hales
Angela M
AM
Vincent
Lisa N
LN
Overbeek
Paul A
PA
Chamberlain
Coral G
CG
McAvoy
John W
JW
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D046508:Culture Techniques; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007903:Lens Capsule, Crystalline / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000009:adverse effects* / Q000235:genetics / Q000502:physiology
D015415:Biomarkers; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta