Cataract induction in lenses cultured with transforming growth factor-beta.
OBJECTIVE
Anterior subcapsular cataracts are characterized by the appearance of opaque plaques of abnormal cells. Distinctive spindle-shaped cells containing alpha-smooth muscle actin are present and are associated with wrinkling of the overlying lens capsule. Accumulations of extracellular matrix, including type I collagen, also are found. The authors previously reported that transforming growth factor-beta (TGF-beta) induces similar aberrant morphologic changes in lens epithelial explants. More recently, they identified alpha-smooth muscle actin in explants cultured with TGF-beta. The aim of this study was to determine whether TGF-beta induces comparable cataractous changes in whole lenses and to examine the effects of this treatment on the transparency of the lens.


METHODS
Whole lenses from 21-day-old rats were cultured in defined serum-free medium with TGF-beta 2 or without added growth factors for 5 days. Lenses were then photographed and prepared for histology and immunolocalization.


RESULTS
Lenses cultured with TGF-beta developed distinct anterior opacities just beneath the lens capsule. Histologically, clumps of abnormal cells corresponded with these opacities. Spindle-shaped cells, which contained alpha-smooth muscle actin, were present, and the overlying capsule was often wrinkled. The clumps contained accumulations of type I collagen, laminin, and heparan sulphate proteoglycan. In contrast, lenses cultured without growth factors remained transparent, retained normal lens morphology, and did not accumulate alpha-smooth muscle actin or type I collagen.


CONCLUSIONS
These results show that TGF-beta induces whole lenses to form opacities that contain morphologic and biochemical markers for subcapsular cataract.
Hales
A M
AM
Department of Anatomy and Histology, University of Sydney, New South Wales, Australia.
Chamberlain
C G
CG
McAvoy
J W
JW
D000199:Actins / Q000378:metabolism; D000818:Animals; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D016895:Culture Media, Serum-Free; D005455:Fluorescent Antibody Technique; D007903:Lens Capsule, Crystalline / Q000473:pathology; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000199:Actins; D016895:Culture Media, Serum-Free; D016212:Transforming Growth Factor beta; D003094:Collagen