Minocycline decreases CCR2-positive monocytes in the retina and ameliorates photoreceptor degeneration in a mouse model of retinitis pigmentosa.
Minocycline decreases CCR2-positive monocytes in the retina and ameliorates photoreceptor degeneration in a mouse model of retinitis pigmentosa.
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DOI：
10.1371/journal.pone.0239108
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Nakano T
中科院分区：
文献类型：
--
作者：
Terauchi R;Kohno H;Watanabe S;Saito S;Watanabe A;Nakano T
视网膜炎症加速视网膜变性引起的感光细胞死亡。二甲胺四环素是一种半合成的广谱四环素抗生素，先前有报道称其可挽救视网膜变性中光感受器细胞的死亡。我们使用c-mer原癌基因酪氨酸激酶(Mertk)−/−Cx3cr1GFP/+Ccr2RFP/+小鼠检测米诺环素对视网膜光感受器变性的影响，从而通过荧光观察cx3cr1 -绿色荧光蛋白(GFP)-和ccr2 -红色荧光蛋白（RFP）阳性的巨噬细胞。6周龄时，Mertk−/−Cx3cr1GFP/+Ccr2RFP/+小鼠视网膜出现光感受器变性，外视网膜和视网膜下空间出现GFP和rfp阳性巨噬细胞的积累。Mertk−/−Cx3cr1GFP/+Ccr2RFP/+小鼠腹腔注射米诺环素。二甲胺四环素治疗后，CCR2-RFP阳性细胞数量明显减少。此外，在Mertk−/−Cx3cr1GFP/+Ccr2RFP/+小鼠中，经TUNEL检测，二甲胺四环素可部分逆转外核层变薄，减少凋亡细胞数量。综上所述，我们发现米诺环素改善了Mertk基因缺失导致的遗传性光感受器变性模型中的光感受器细胞死亡，并对CCR2阳性巨噬细胞有抑制作用，这可能是米诺环素的一种神经保护机制。
Retinal inflammation accelerates photoreceptor cell death caused by retinal degeneration. Minocycline, a semisynthetic broad-spectrum tetracycline antibiotic, has been previously reported to rescue photoreceptor cell death in retinal degeneration. We examined the effect of minocycline on retinal photoreceptor degeneration using c-mer proto-oncogene tyrosine kinase (Mertk)−/−Cx3cr1GFP/+Ccr2RFP/+ mice, which enabled the observation of CX3CR1-green fluorescent protein (GFP)- and CCR2-red fluorescent protein (RFP)-positive macrophages by fluorescence. Retinas of Mertk−/−Cx3cr1GFP/+Ccr2RFP/+ mice showed photoreceptor degeneration and accumulation of GFP- and RFP-positive macrophages in the outer retina and subretinal space at 6 weeks of age. Mertk−/−Cx3cr1GFP/+Ccr2RFP/+ mice were intraperitoneally administered minocycline. The number of CCR2-RFP positive cells significantly decreased after minocycline treatment. Furthermore, minocycline administration resulted in partial reversal of the thinning of the outer nuclear layer and decreased the number of apoptotic cells, as assessed by the TUNEL assay, in Mertk−/−Cx3cr1GFP/+Ccr2RFP/+ mice. In conclusion, we found that minocycline ameliorated photoreceptor cell death in an inherited photoreceptor degeneration model due to Mertk gene deficiency and has an inhibitory effect on CCR2 positive macrophages, which is likely to be a neuroprotective mechanism of minocycline.
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影响因子：
9.3
作者：
Kohno H;Koso H;Okano K;Sundermeier TR;Saito S;Watanabe S;Tsuneoka H;Sakai T
通讯作者：
Sakai T
影响因子：
4.6
作者：
Ronning, Kaitryn E.;Kaden, Sarah J.;Burns, Marie E.
通讯作者：
Burns, Marie E.
DOI：
10.4049/jimmunol.1301738
发表时间：
2014-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kohno H;Maeda T;Perusek L;Pearlman E;Maeda A
通讯作者：
Maeda A
影响因子：
32.4
作者：
O'Koren, Emily G.;Yu, Chen;Saban, Daniel R.
通讯作者：
Saban, Daniel R.
影响因子：
4.3
作者：
Saban, Daniel R.
通讯作者：
Saban, Daniel R.