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Differential cataractogenic potency of TGF-beta1, -beta2, and -beta3 and their expression in the postnatal rat eye
C Gordon-Thomson1, R U de Iongh, A M Hales
1Department of Anatomy and Histology and Institute for Biomedical Research (F13), The University of Sydney, NSW, Australia.
Purpose:
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.
Insights
Transforming growth factor-beta (TGF-β) isoforms 1, 2, and 3 can all induce cataract-like changes in rat lenses. TGF-β2 and TGF-β3 are more potent cataractogenic agents than TGF-β1.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Transforming growth factor-beta (TGF-β) is implicated in cataract development.
- The specific roles of different TGF-β isoforms in cataractogenesis are not fully understood.
Purpose of the Study:
- To compare the cataractogenic potential of TGF-β1, TGF-β2, and TGF-β3.
- To investigate the expression patterns of TGF-β isoforms within the rat eye.
Main Methods:
- Cultured rat lens epithelial explants and whole lenses with varying concentrations of TGF-β1, TGF-β2, and TGF-β3.
- Monitored for cataractous changes using phase contrast microscopy.
- Detected cataract markers (alpha-smooth muscle actin, type I collagen) and TGF-β expression via immunofluorescence and in situ hybridization.
Main Results:
- All three TGF-β isoforms induced morphologic changes consistent with subcapsular cataract.
- TGF-β2 and TGF-β3 were approximately 10 times more potent than TGF-β1.
- Distinct but overlapping expression patterns of TGF-β isoforms and their mRNA were observed in ocular tissues, with TGF-β1 and TGF-β2 widely detected, and TGF-β3 mRNA primarily in the retina and choroid.
Conclusions:
- All TGF-β isoforms are present in the eye and can potentially induce cataractous changes.
- TGF-β activity appears to be tightly regulated in the eye.
- Activation of TGF-β in the lens during injury or disease may contribute to cataract formation.