Collagen gene expression and the altered accumulation of scleral collagen during the development of high myopia
Collagen gene expression and the altered accumulation of scleral collagen during the development of high myopia
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DOI：
10.1074/jbc.m300970200
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发表时间：
2003-05-09
影响因子：
4.8
通讯作者：
McBrien, NA
中科院分区：
文献类型：
--
作者：
Gentle, A;Liu, YY;McBrien, NA
在人类和动物模型中，高度近视的发展与巩膜胶原积累减少、巩膜变薄和巩膜组织损失相关。高度近视眼的巩膜中也观察到胶原纤维直径减小。本研究调查了高度近视哺乳动物模型中巩膜胶原合成和降解的方面，以阐明巩膜变化的潜在因素。在单眼剥夺树鼩巩膜胶原的一般合成和降解进行了研究，通过在体内管理[H-3]脯氨酸和随后的测定巩膜组织的[H-3]胶原。此外，PCR富集的cDNA，从树鼩巩膜mRNA产生的，用于合成探针杂交到定制的基因阵列组成的11个胶原亚型的部分序列。最后，采用实时荧光定量逆转录-PCR技术研究了近视眼、对侧对照眼和正常树鼩眼巩膜中I型、III型和V型胶原mRNA的表达。单眼剥夺5天后，近视眼后极巩膜[H-3]脯氨酸掺入减少（-36+/-4%），而[H-3]脯氨酸含量在近视诱导前在治疗眼和对照眼中相似（-1+/-8%），但在近视眼中减少5（-8+/-2%），12（-15+/-4%）和24（-10+/-4%）天的近视诱导。大多数研究的胶原蛋白被发现在巩膜中表达，鉴定出11种亚型。I型胶原mRNA在近视眼巩膜中的表达减少（-20+/-7%），然而，III型胶原（+2+/-9%）和V型胶原（-1+/-6%）表达相对于对照没有变化，导致III型胶原/I型胶原和V型胶原/I型胶原的表达比率净增加（分别为22%和25%）。这些结果表明，近视眼中巩膜胶原积累减少是胶原合成减少和胶原降解加速的结果。此外，胶原蛋白合成的变化是由I型胶原蛋白产生减少驱动的。新合成的胶原蛋白III型/I型和V型/I型的比率的短期增加可能在高度近视中观察到的小直径巩膜胶原纤维的频率增加中是重要的，并且可能在患有病理性近视的人中的后葡萄肿的后续发展中是重要的。
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 [H-3] proline and subsequent assay of scleral tissue for [H-3] 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 [H-3] proline incorporation was reduced at the posterior pole of myopic eyes following 5 days of monocular deprivation (-36+/-4%), whereas [H-3] 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.