Troger Josef, Doblinger Alfred, Leierer Johannes, Laslop Andrea, Schmid Eduard, Teuchner Barbara, Opatril Markus, Philipp Wolfgang, Klimaschewski Lars, Pfaller Kristian, Göttinger Wolfgang, Fischer-Colbrie Reiner
Department of Ophthalmology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Invest Ophthalmol Vis Sci. 2005 Feb;46(2):647-54. doi: 10.1167/iovs.04-0425.
To evaluate whether secretoneurin represents a sensory neuropeptide innervating the anterior segment of the eye.
The presence and distribution of secretoneurin was investigated in human eyes by radioimmunoassay and immunofluorescence and compared with that of the rat eye. The source of secretoneurin-positive nerves in the eye was established by measuring the concentration in eye tissues, the trigeminal and superior cervical ganglia both in control rats and in rats treated with capsaicin, and by performing immunofluorescence in one rat subjected to sympathectomy. In the rat trigeminal ganglion, the corresponding mRNA was verified by in situ hybridization and the processing of secretogranin II into secretoneurin by gel filtration chromatography.
In human eyes, the highest levels of the peptide were found in the choroid. Nerve fibers were visualized in both species in the upper corneal and limbal stroma; in the trabecular meshwork; in the ciliary muscle, the ciliary body stroma, and processes; and in clear association with the dilator muscle, which disappeared after sympathetic denervation in rats; and also innervating the sphincter muscle in the iris and the choroidal stroma and surrounding blood vessels. Significant amounts of secretoneurin were present in the rat trigeminal ganglion and rat eye tissues. Capsaicin pretreatment led to a 57.0% +/- 4.3% and 59.1% +/- 11.9% decrease of the concentration in the trigeminal ganglion and the iris/ciliary body complex, respectively. Despite high levels in the rat superior cervical ganglion, sympathetic denervation failed to lower the concentration in eye tissues. The secretogranin II probe labeled numerous small-sized ganglion cells within the rat trigeminal ganglion, and the precursor of the peptide was found to become completely processed into secretoneurin.
Apart from the sympathetically innervated dilator muscle, there is unequivocal evidence that secretoneurin represents a constituent of capsaicin-sensitive sensory neurons in the rat trigeminal ganglion and of unmyelinated C-fibers in the rat iris/ciliary body complex, which indicates a participation of this peptide in the ocular irritative response, a model for neurogenic inflammation in lower mammals. Because of the association of nerves with blood vessels and potent angiogenic properties, secretoneurin may be involved in neovascularization processes.
评估分泌神经素是否代表支配眼前节的感觉神经肽。
通过放射免疫分析和免疫荧光法研究人眼和大鼠眼中分泌神经素的存在及分布，并进行比较。通过测量对照大鼠和辣椒素处理大鼠的眼组织、三叉神经节和颈上神经节中的浓度，以及对一只进行交感神经切除术的大鼠进行免疫荧光，确定眼中分泌神经素阳性神经的来源。在大鼠三叉神经节中，通过原位杂交验证相应的信使核糖核酸，并通过凝胶过滤色谱法将分泌粒蛋白II加工成分泌神经素。
在人眼中，该肽水平最高的部位是脉络膜。在两种动物的角膜上皮和角膜缘基质、小梁网、睫状肌、睫状体基质和睫状突中均可见神经纤维；与瞳孔开大肌明显相关，在大鼠交感神经去神经支配后消失；还支配虹膜中的瞳孔括约肌、脉络膜基质和周围血管。大鼠三叉神经节和眼组织中存在大量分泌神经素。辣椒素预处理导致三叉神经节和虹膜/睫状体复合体中的浓度分别降低57.0%±4.3%和59.1%±11.9%。尽管大鼠颈上神经节中的水平较高，但交感神经去神经支配未能降低眼组织中的浓度。分泌粒蛋白II探针标记了大鼠三叉神经节内许多小尺寸的神经节细胞，并且发现该肽的前体完全加工成了分泌神经素。
除了受交感神经支配的瞳孔开大肌外，有明确证据表明分泌神经素是大鼠三叉神经节中对辣椒素敏感的感觉神经元以及大鼠虹膜/睫状体复合体中无髓鞘C纤维的组成成分，这表明该肽参与了眼刺激反应，这是低等哺乳动物神经源性炎症的一种模型。由于神经与血管的关联以及强大的血管生成特性，分泌神经素可能参与新生血管形成过程。
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