Rescue of photoreceptors from the damaging effects of constant light by midkine, a retinoic acid-responsive gene product.

Rescue of photoreceptors from the damaging effects of constant light by midkine, a retinoic acid-responsive gene product.
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DOI:
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发表时间:
1994-11
影响因子:
4.4
通讯作者:
K. Unoki;N. Ohba;H. Arimura;H. Muramatsu;T. Muramatsu
K. Unoki;N. Ohba;H. Arimura;H. Muramatsu;T. Muramatsu
中科院分区:
医学2区
文献类型:
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作者:
K. Unoki;N. Ohba;H. Arimura;H. Muramatsu;T. Muramatsu

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目的探讨视黄酸反应基因产物中期因子(MK)对持续光照诱导的SD大鼠视网膜变性的保护作用。方法在持续光照前2d玻璃体腔注射中期因子、碱性成纤维细胞生长因子、MK+肝素或缓冲液对照。连续光照7d后,眼内注入固定剂,沿垂直经线一分为二,石蜡包埋,切片。石蜡包埋切片通过细胞学分析、测量外核层厚度(ONL)和巨噬细胞计数来评估视网膜光损伤的程度。结果持续光照1周后,对照组和注射磷酸盐缓冲液(PBS)的对照组光感受器内外节段大部分丢失,ONL厚度变薄。注射MK或bFGF的眼在光感受器层有显著的挽救作用,ONL厚度增加了两到三倍。注射MK的眼巨噬细胞数与对照组相比明显减少。与对照组相比,注射碱性成纤维细胞生长因子的患者数量增加了1.5倍。结论中期因子在持续光照诱导的视网膜变性中表现出较强的促存活活性,在体内具有较高的神经营养活性。
PURPOSE To evaluate the protective effects of midkine (MK), the product of a retinoic acid-responsive gene, on constant light-induced retinal degeneration in albino Sprague-Dawley rats. METHODS Midkine, basic fibroblast growth factor (bFGF), MK plus heparin, or buffer controls were injected intravitreally 2 days before constant light exposure. After 7 days of continuous light exposure, the eyes were perfused with fixative, bisected along the vertical meridian, embedded in paraffin, and sectioned. The degree of retinal light damage was assessed for paraffin-embedded sections by cytologic analysis, by measuring the thickness of the outer nuclear layer (ONL), and by counting the number of macrophages. RESULTS After 1 week of constant light exposure, uninjected controls and those injected with phosphate-buffered saline (PBS) lost most of the photoreceptor inner and outer segments, and the thickness of the ONL was decreased. Eyes that were injected with MK or bFGF demonstrated a significant rescue in the photoreceptor layer with a two- to threefold increase in the ONL thickness. The number of macrophages in eyes injected with MK was significantly suppressed compared with controls. Those injected with bFGF had a 1.5-fold increase in number compared with controls. CONCLUSIONS Midkine has shown strong survival-promoting activity in constant light-induced retinal degeneration, and thus has a high degree of neurotrophic activity in vivo.