Differential cataractogenic potency of TGF-beta1, -beta2, and -beta3 and their expression in the postnatal rat eye.
OBJECTIVE
Transforming growth factor-beta has been shown to induce cataractous changes in rat lenses. This study assesses the relative cataractogenic potential of TGF-beta1, TGF-beta2, and TGF-beta3 and their expression patterns in the rat eye.


METHODS
Lens epithelial explants and whole lenses from weanling rats were cultured with TGF-beta1, TGF-beta2, or TGF-beta3 at concentrations ranging from 0.025 ng/ml to 4 ng/ml for 3 to 5 days. Cataractous changes were monitored daily by phase contrast microscopy and by immunofluorescent detection of cataract markers alpha-smooth muscle actin and type I collagen. Expression of TGF-beta was studied by immunofluorescence and in situ hybridization on eye sections from neonatal and weanling rats.


RESULTS
All three isoforms induced morphologic changes in lens epithelial explants and cultured lenses that are typically associated with human subcapsular cataract. Transforming growth factor-beta2 and TGF-beta3 were approximately 10 times more potent than TGF-beta1. All three isoforms were expressed in the eye in spatially distinct but overlapping patterns. Transforming growth factor-beta1 and TGF-beta2 and their mRNA were detected in most ocular tissues, including the lens. Although TGF-beta3 was immunolocalized in lens epithelium and fibers and in other ocular tissues, its mRNA was detected only in the retina and choroid.


CONCLUSIONS
All three isoforms of TGF-beta are potentially available to lens cells and have the potential to induce cataractous changes. The results suggest that TGF-beta activity is normally tightly regulated in the eye. Activation of TGF-beta in the lens environment, such as may occur during injury, in wound healing, or in pathologic conditions may contribute to cataractogenesis in vivo.
Gordon-Thomson
C
C
Department of Anatomy and Histology and Institute for Biomedical Research (F13), The University of Sydney, NSW, Australia.
de Iongh
R U
RU
Hales
A M
AM
Chamberlain
C G
CG
McAvoy
J W
JW
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008858:Microscopy, Phase-Contrast; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*
D000199:Actins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen