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J. Biol. Chem., Vol. 278, Issue 19, 16587-16594, May 9, 2003
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From the Department of Optometry and Vision Sciences, The
University of Melbourne, Victoria 3010, Australia
The development of high myopia is
associated with reduced scleral collagen accumulation, scleral
thinning, and loss of scleral tissue, in both humans and animal models.
Reduced collagen fibril diameter is also observed in the sclera of eyes
with high myopia. The present study investigated aspects of scleral
collagen synthesis and degradation, in a mammalian model of high
myopia, to elucidate the factors underlying scleral changes.
General synthesis and degradation of scleral collagen was investigated
in monocularly deprived tree shrews, through the in vivo
administration of [3H]proline and subsequent assay of
scleral tissue for [3H]collagen. In addition, PCR
enriched cDNA, produced from tree shrew scleral mRNA, was used
to synthesize probes for hybridization to custom gene arrays consisting
of partial sequences for 11 collagen subtypes. Finally, real-time
reverse transcriptase-PCR was employed to investigate collagen
type I, III, and V mRNA expression in the sclera of myopic,
contralateral control, and normal tree shrew eyes. Scleral
[3H]proline incorporation was reduced at the posterior
pole of myopic eyes following 5 days of monocular deprivation
(
Collagen Gene Expression and the Altered Accumulation of Scleral
Collagen during the Development of High Myopia*
36 ± 4%), whereas [3H]proline content was
similar in treated and control eyes before myopia induction (1 ± 8%) but was reduced in myopic eyes following 5 (8 ± 2%),
12 (15 ± 4%), and 24 (10 ± 4%) days of myopia
induction. The majority of the collagens investigated were found to be
expressed in the sclera, with 11 subtypes being identified. Collagen
type I mRNA expression was reduced in the sclera of myopic eyes
(20 ± 7%), however, collagen type III (+2 ± 9%) and
type V (1 ± 6%) expression was unchanged relative to control,
resulting in a net increase in the ratio of expression of collagen type
III/type I and collagen type V/type I (22 and 25%, respectively).
These results show that reduced scleral collagen accumulation in myopic eyes is a result of both decreased collagen synthesis and accelerated collagen degradation. Furthermore, changes in collagen synthesis are
driven by reduced type I collagen production. Short term increases in
the ratio of newly synthesized collagen type III/type I and type V/type
I are likely to be important in the increasing frequency of small
diameter scleral collagen fibrils observed in high myopia and may be
important in the subsequent development of posterior staphyloma in
humans with pathological myopia.
*
This work was supported by National Health and Medical
Research Council of Australia Grant 145700 and Australian Research Council Grant S0005254.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Optometry
and Vision, Sciences, The University of Melbourne, Victoria 3010, Australia. Tel.: 61-3-8344-7001; Fax: 61-3-9349-7474; E-mail: n.mcbrien@optometry.unimelb.edu.au.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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