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A role of transforming growth factor-beta 1 in the control of corneal neovascularization
1Department of Ophthalmology, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Abstract:
Transforming growth factor beta 1 (TGF-beta 1) has been implicated in both the stimulation of angiogenesis in vivo and in the inhibition of endothelial cell proliferation in vitro systems. In this study we present evidence showing that under certain experimental conditions TGF-beta 1 may inhibit neovascularization in vivo. TGF-beta 1 was incorporated into ethylene vinyl acetate copolymer (Elvax 40) matrixes which provide a valuable vehicle for the controlled and sustained delivery of bioactive peptides. The biological effectiveness of TGF-beta 1 sequestered in polymer matrices was assessed by measuring the inhibition of [3H]-thymidine incorporation into the DNA of cultured mink lung epithelial cells. Neovascularization was induced in both corneas of albino rabbits by one deep-seated limbal silk suture. Elvax 40 matrixes loaded with TGF-beta 1 (release rate, 1.66 ng/24 h) were implanted in rabbit corneal stroma. "Empty" polymers in the contralateral eye served as controls. Aliquots of aqueous fluid were withdrawn, and the presence activity of phagocytic cells was assessed by the production of superoxide anion (O2) which was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome C. Polymer-enclosed TGF-beta 1 implanted in rabbit corneas significantly suppressed angiogenesis (2.65 +/- 0.4 mm compared to 3.05 +/- 0.3 mm in contralateral controls p < 0.05). Superoxide production in 100 microliters aliquots of aqueous fluid was 0.95 +/- 0.18 and 0.6 +/- 0.18 nmol O2/10 min in control eyes and in the eyes bearing sequestered TGF-beta 1, respectively (p < 0.02). These results indicate that under the experimental conditions selected in this study, TGF-beta 1 significantly suppressed in vivo angiogenesis.
Insights
Transforming growth factor beta 1 (TGF-beta 1) delivered via polymer matrices was found to inhibit in vivo angiogenesis in rabbit corneas. This study demonstrates TGF-beta 1
Area of Science:
- Biochemistry
- Cell Biology
- Ophthalmology
Background:
- Transforming growth factor beta 1 (TGF-beta 1) exhibits dual roles in angiogenesis, stimulating it in vivo while inhibiting endothelial cell proliferation in vitro.
- Controlled delivery systems are crucial for studying the localized effects of bioactive peptides like TGF-beta 1.
Purpose of the Study:
- To investigate the in vivo effect of sustained TGF-beta 1 delivery on neovascularization.
- To assess the anti-angiogenic potential of TGF-beta 1 when sequestered in a polymer matrix.
Main Methods:
- TGF-beta 1 was incorporated into ethylene vinyl acetate copolymer (Elvax 40) matrices for sustained release.
- Neovascularization was induced in rabbit corneas using silk sutures, with TGF-beta 1-loaded polymers implanted in the stroma.
- Angiogenesis was quantified, and phagocytic cell activity (superoxide anion production) was measured in aqueous humor.
Main Results:
- Polymer-enclosed TGF-beta 1 significantly suppressed corneal angiogenesis compared to controls (2.65 +/- 0.4 mm vs. 3.05 +/- 0.3 mm, p < 0.05).
- Superoxide production, an indicator of phagocytic cell activity, was significantly reduced in eyes treated with TGF-beta 1 (0.6 +/- 0.18 nmol O2/10 min vs. 0.95 +/- 0.18 nmol O2/10 min, p < 0.02).
Conclusions:
- Sustained, localized delivery of TGF-beta 1 using Elvax 40 matrices effectively inhibits in vivo angiogenesis in a rabbit corneal model.
- These findings highlight a potential therapeutic strategy for controlling pathological neovascularization.