Abstract | PURPOSE: METHODS: To assess the possible gelatinase modulation after AA treatment, a single subconjunctival injection of AA (300 microg) was delivered to the right eyes of 10-week-old LH(BETA)T(AG) mice. Eyes were evaluated for gelatinase expression and activity by gel and in situ zymography at 24 hours, 48 hours, and 1 week after treatment. RESULTS: Gel zymography of whole eye extracts and in situ zymography of retinal tumors showed strong gelatinase expression and activity within transgenic RB tumors. AA treatment in RB transgenic mice resulted in a significant decrease of gelatinase activity 1 week after AA treatment. Surprisingly, there was an initial transient upregulation of MMP-9 activity in whole eye extracts at 24 and 48 hours after AA treatment in both LH(BETA)T(AG) transgenic and wild-type mice. This increase was not observed in the tumors. CONCLUSIONS: As suggested by our data, inhibition of gelatinase activity appears to be a mechanism of action of AA. AA treatment results in a decrease in gelatinase activity that correlates with the significant decrease in tumor burden shown by the authors' previous studies. However, the significance of the initial, transient upregulation of gelatinase by AA injection is unknown, and further studies are warranted. Combining antiangiogenic agents with multiple mechanisms of action has the potential to enhance RB tumor control.
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Authors | M Livia Bajenaru, Yolanda Piña, Timothy G Murray, Colleen M Cebulla, William Feuer, Maria-Elena Jockovich, Maria-Encarna Marin Castaño |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 51
Issue 6
Pg. 2860-4
(Jun 2010)
ISSN: 1552-5783 [Electronic] United States |
PMID | 20107171
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Pregnadienediols
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
- anecortave acetate
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Topics |
- Angiogenesis Inhibitors
(therapeutic use)
- Animals
- Disease Models, Animal
- Electrophoresis, Polyacrylamide Gel
- Fluorescent Antibody Technique, Indirect
- Matrix Metalloproteinase 2
(metabolism)
- Matrix Metalloproteinase 9
(metabolism)
- Mice
- Mice, Transgenic
- Pregnadienediols
(therapeutic use)
- Retinal Neoplasms
(drug therapy, enzymology, pathology)
- Retinoblastoma
(drug therapy, enzymology, pathology)
- Up-Regulation
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