gentle-isoformspecific-2004.pdf (139.65 kB)
Isoform-specific changes in scleral transforming growth factor-beta expression and the regulation of collagen synthesis during myopia progression
journal contribution
posted on 2004-04-30, 00:00 authored by A I Jobling, M Nguyen, Alex GentleAlex Gentle, N A McBrienThe development of high myopia is associated with altered scleral extracellular matrix biochemistry. Previous studies highlight the importance of collagen turnover in this process, yet it is unclear which factors control scleral remodeling. This study used a mammalian model of myopia to investigate the capacity of TGF (transforming growth factor)-beta1, -beta2, and -beta3 to influence scleral remodeling in myopia. RT-PCR confirmed the presence of all mammalian TGF-beta isoforms in scleral tissue and scleral fibroblasts. Myopia was experimentally induced via monocular deprivation of pattern vision, and animals were allocated to two groups depending on the duration of treatment (1 or 5 days). Down-regulation of each isoform was apparent after only 1 day of myopia development (TGF-beta1, -32%; TGF-beta2, -27%; TGF-beta3, -42%). Whereas the decrease in TGF-beta1 and -beta3 expression was relatively constant between the two time points, differential down-regulation of TGF-beta2 was found between days 1 (-27%) and 5 (-50%). In vitro experiments, using primary scleral fibroblasts, demonstrated the capacity of all isoforms to increase collagen production in a dose-dependent manner. Changes in TGF-beta levels, which mimicked those during myopia induction, caused an approximately 15% reduction in collagen synthesis, which is qualitatively similar to those previously reported in vivo. These data represent the first demonstration of TGF-beta3 expression in the sclera and implicate all three TGF-beta isoforms in the control of scleral remodeling during myopia development. In addition, the early alterations in TGF-beta expression levels may reflect a role for these cytokines in mediating the retinoscleral signal that controls myopic eye growth.
History
Journal
Journal of biological chemistryVolume
279Issue
18Pagination
18121 - 18126Publisher
American Society for Biochemistry and Molecular BiologyLocation
Rockville, Md.Publisher DOI
Link to full text
ISSN
0021-9258eISSN
1083-351XLanguage
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2004, The American Society for Biochemistry and Molecular Biology, Inc.Usage metrics
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