Development of normal and injury-induced gene expression of aFGF, bFGF, CNTF, BDNF, GFAP and IGF-I in the rat retina

Development of normal and injury-induced gene expression of aFGF, bFGF, CNTF, BDNF, GFAP and IGF-I in the rat retina
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DOI:
10.1006/exer.2001.0990
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发表时间:
2001-05-01
影响因子:
3.4
通讯作者:
Lavail, MM
Lavail, MM
中科院分区:
医学3区
文献类型:
--
作者:
Cao, W;Li, F;Lavail, MM

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视网膜的局灶性机械损伤会显着增加碱性成纤维细胞生长因子 (bFGF) 和睫状神经营养因子 (CNTF) mRNA 的表达,并伴有 FGFR-1 mRNA 的短暂增加,这种反应被认为可以保护损伤部位附近的光感受器免受遗传性和光诱导的视网膜变性。我们现在已经检查了正常大鼠对损伤反应所涉及的主要生存因子的视网膜基因表达,作为正常和受损视网膜中出生后年龄的函数。在出生后第10、23、35、60、90、120和180天(P),通过视网膜针切口使Sprague-Dawley大鼠的一只眼睛受伤。另一只眼睛未受伤并作为对照。受伤后 1 天拍摄视网膜。进行Northern印迹分析以确定以下因子和受体的mRNA表达:bFGF和酸性成纤维细胞生长因子(aFGF)和FGF受体-1(FGFR-1); CNTF和CNTF受体α(CNTFR-α);脑源性神经营养因子(BDNF)及其受体 trkB;以及胰岛素样生长因子-I (IGF-I) 和 IGF-I 受体 (IGF-IR);胶质纤维酸性蛋白(GFAP)和视蛋白,在未受伤的对照眼中,大多数因子的mRNA表达随着出生后年龄的增加而增加,在P10时表达很少,在P21(视蛋白)、P35(aFGF)、P60(BDNF)或P90(bFGF、FGFR-1、CNTF和GFAP)时达到最大表达水平。相反,IGF-1 mRNA从P10的高表达水平迅速下降到P22时该水平的约55%,并在P35及之后达到稳定的P10水平的45-50%。 bFGF、FGFR-1、CNTF 和 GFAP mRNA 对损伤的反应随着出生后年龄的增加而增强。出乎意料的是,在 P35 之前仅观察到与对照眼中观察到的 bFGF、FGFR-1、CNTF 和 GFAP 相比的最小增加。此后。损伤后bFGF mRNA的增加在P60时达到最大3倍,维持该水平至P120,并在P180时略微下降至2.5倍。 FGFR-1 mRNA 的表达在 P90 时最大增加 2.6 倍。 CNTF 和 GFAP mRNA 的表达遵循与 bFGF 相似的时间过程。机械损伤不会改变 aFGF、BDNF、IGF-I 以及受体、CNTFR-α、trkB 和 IGF-IR 的 mRNA 水平。这些数据表明,在出生后早期,对损伤的反应最小,但随着年龄的增长而增加,大多数潜在生存因素在 P60-90 时达到峰值。 (C) 2001 年学术出版社。
Focal mechanical injury to the retina substantially increases basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF) mRNA expression, accompanied by a transient increase in FGFR-1 mRNA, and this response is thought to protect photoreceptors near the injury site from inherited and light-induced retinal degenerations. We have now examined retinal gene expression of the principal survival factors involved in the response to injury in normal rats as a function of postnatal age both in normal and injured retinas. Sprague-Dawley rats were injured in one eye by needle incision through the retina at postnatal day (P) 10, 23, 35, 60, 90, 120 and 180. The other eye was uninjured and served as the control. Retinas were taken 1 day post-injury. Northern blot analysis was performed to determine the mRNA expression of the following factors and receptors: bFGF and acidic fibroblast growth factors (aFGF) and FGF receptor-1 (FGFR-1); CNTF and CNTF receptor alpha (CNTFR-alpha); brain-derived neurotrophic factor (BDNF) and its receptor trkB; and insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR); glial fibrillary acidic protein (GFAP) and opsin, In the uninjured control eyes, mRNA expression of most of the factors increased with, postnatal age, with little expression at P10 and maximal expression levels reached at P21 (opsin), P35 (aFGF), P60 (BDNF) or P90 (bFGF, FGFR-1, CNTF and GFAP). In contrast, IGF-1 mRNA rapidly decreased from a high level of expression at P10 to about 55 % of that level by P22, reaching a stable 45-50 % of the P10 level at P35 and thereafter. The response to injury of bFGF, FGFR-1, CNTF and GFAP mRNAs increased with postnatal age. Unexpectedly, only minimal increases in bFGF, FGFR-1, CNTF and GFAP over those seen in the control eyes were observed before P35. Thereafter. the increase of bFGF mRNA after injury reached a maximum of three-fold at P60, maintained this level to P120, and slightly decreased to 2.5-fold by P180. Expression of FGFR-1 mRNA showed a maximum increase of 2.6-fold at P90. Expression of CNTF and GFAP mRNAs followed a time course similar to that of bFGF. Mechanical injury did not alter the mRNA levels of aFGF, BDNF, IGF-I, and receptors, CNTFR-alpha, trkB and IGF-IR. These data show that the response to injury is minimal at early postnatal ages but increases with age and peaks at P60-90 for most potential survival factors. (C) 2001 Academic Press.