Gradients of cone differentiation and FGF expression during development of the foveal depression in macaque retina
Gradients of cone differentiation and FGF expression during development of the foveal depression in macaque retina
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DOI：
10.1017/s0952523805224069
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发表时间：
2005-07-01
影响因子：
1.9
通讯作者：
Provis, JM
中科院分区：
文献类型：
--
作者：
Cornish, EE;Madigan, MC;Provis, JM
成年灵长类视网膜中心凹内的视锥细胞比黄斑中心凹边缘的视锥细胞更窄、更长，而黄斑中心凹边缘的视锥细胞又比更偏心的视锥细胞更窄、更长。视锥形态的这种梯度与视锥密度和锐度直接相关。在这里，我们研究了成纤维细胞生长因子信号转导中心凹视锥细胞形态分化的假说，特别是调节中心凹视锥细胞伸长的机制。本研究采用免疫组织化学方法，对95~2.5岁恒河猴视网膜水平经络的视锥延伸进行了定量研究。我们还用原位杂交和免疫组织化学方法研究了FGF2和FGFR1-4在发育中的黄斑中心凹和水平经络的其他三个样本位置的表达模式。用荧光标记“快速红”(Roche)检测标记的RNA，用共聚焦显微镜、光密度计比较锥体内节段和神经节细胞层(GCL)的表达水平，并进行统计学意义检验。我们的结果表明，视锥细胞的形态分化大约在FD95前后开始于视盘附近，直到出生前一直向发育中的中心凹发展。在此期间，与更靠近视盘的视锥细胞相比，FGF2和FGFR4 mRNAs在中心凹视锥中的表达水平较低。在同一切片的神经节细胞层中，FGF2mRNA的表达没有类似的梯度。中心凹视锥的成熟被推迟到出生后时期。结果表明，在猕猴妊娠的后半段，视锥分化波从视盘区向发育中的中心凹扩散。与分化波相关的FGFR4和FGF2的表达梯度表明，成纤维细胞生长因子信号调节锥体的狭窄和延长。
Cones in the foveola of adult primate retina are narrower and more elongated than cones oil the foveal rim, which in turn, are narrower and more elongated than those located more eccentric. This gradient of cone morphology is directly cot-related with cone density and acuity. Here we investigate the hypothesis that fibroblast growth factor (FGF) signaling mediates the morphological differentiation of foveal cones-in particular, the mechanism regulating the elongation of foveal cones. We used immunoreactivity to FGF receptor (R) 4, and quantitative analysis to Study cone elongation oil the horizontal meridian of macaque retinae, aged between foetal day (Fd) 95 and 2.5 years postnatal (P 2.5y). We also used in situ hybridization and immunohistochemistry to investigate the expression patterns of FGF2 and FGFR1-4 at the developing fovea, and three other sample locations oil the horizontal meridian. Labeled RNA was detected using the fluorescent marker "Fast Red" (Roche) and levels of expression in cone inner segments and in the ganglion cell layer (GCL) were compared using confocal microscopy, optical densitometry, and tested for statistical significance. Our results show that morphological differentiation of cones begins near the optic disc around Fd 95, progressing toward the developing fovea up until birth, approximately. Levels of FGF2 and FGFR4 mRNAs expression are low in foveal cones, compared with cones closer to the optic disc, during this period. There is no similar gradient of FGF2 mRNA expression in the ganglion cell layer of the same sections. Maturation of foveal cones is delayed until the postnatal period. The results suggest that a wave of cone differentiation spreads from the disc region toward the developing fovea during the second half of gestation in the macaque. A gradient of expression of FGFR4 and FGF2 associated with the wave of differentiation suggests that FGF signalling mediates cone narrowing and elongation.