Testing for a gap junction-mediated bystander effect in retinitis pigmentosa: secondary cone death is not altered by deletion of connexin36 from cones.
Testing for a gap junction-mediated bystander effect in retinitis pigmentosa: secondary cone death is not altered by deletion of connexin36 from cones.
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DOI：
10.1371/journal.pone.0057163
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dedek K
中科院分区：
文献类型：
--
作者：
Kranz K;Paquet-Durand F;Weiler R;Janssen-Bienhold U;Dedek K
色素性视网膜炎（RP）是一组遗传性视网膜神经退行性疾病。在细胞水平上，RP导致杆状光感受器的原发性死亡，这是由杆状特异性突变引起的，随后是遗传正常的锥体的继发性变性。不同的机制可能影响细胞死亡从一种光感受器类型到另一种的传播。其中一种机制是间隙连接介导的旁观者效应，即在垂死的视杆细胞中产生的有毒分子通过间隙连接传播，诱导健康的视锥细胞死亡。我们研究了杆锥耦合的破坏是否可以防止二次锥体死亡和减少退化的传播。我们通过将两种不同的视网膜变性小鼠模型（视紫红质敲除和rd1）与connexin36缺陷小鼠杂交来验证这一假设，因为connexin36代表锥体侧的间隙连接蛋白，缺乏connexin36很可能会破坏杆-锥体耦合。利用免疫组织化学方法，我们比较了不同年龄的connexin36缺陷小鼠突变体和表达connexin36的小鼠的锥体变性的进展，并评估了在发病（视紫红质敲除）和继发性锥体死亡（rd1突变体）的后期阶段伴随的形态学变化。connexin36缺失小鼠突变体与表达connexin36的小鼠表现出相同的锥体变性时间和二级神经元形态变化。因此，我们的研究结果表明，连接蛋白36介导的杆-锥体耦合的中断不会阻止、延迟或空间上限制继发性锥体变性，并且表明间隙连接介导的旁观者效应与RP的进展无关。
Retinitis pigmentosa (RP) relates to a group of hereditary neurodegenerative diseases of the retina. On the cellular level, RP results in the primary death of rod photoreceptors, caused by rod-specific mutations, followed by a secondary degeneration of genetically normal cones. Different mechanisms may influence the spread of cell death from one photoreceptor type to the other. As one of these mechanisms a gap junction-mediated bystander effect was proposed, i.e., toxic molecules generated in dying rods and propagating through gap junctions induce the death of healthy cone photoreceptors. We investigated whether disruption of rod-cone coupling can prevent secondary cone death and reduce the spread of degeneration. We tested this hypothesis in two different mouse models for retinal degeneration (rhodopsin knockout and rd1) by crossbreeding them with connexin36-deficient mice as connexin36 represents the gap junction protein on the cone side and lack thereof most likely disrupts rod-cone coupling. Using immunohistochemistry, we compared the progress of cone degeneration between connexin36-deficient mouse mutants and their connexin36-expressing littermates at different ages and assessed the accompanied morphological changes during the onset (rhodopsin knockout) and later stages of secondary cone death (rd1 mutants). Connexin36-deficient mouse mutants showed the same time course of cone degeneration and the same morphological changes in second order neurons as their connexin36-expressing littermates. Thus, our results indicate that disruption of connexin36-mediated rod-cone coupling does not stop, delay or spatially restrict secondary cone degeneration and suggest that the gap junction-mediated bystander effect does not contribute to the progression of RP.
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影响因子：
3.7
作者：
Kaur J;Mencl S;Sahaboglu A;Farinelli P;van Veen T;Zrenner E;Ekström P;Paquet-Durand F;Arango-Gonzalez B
通讯作者：
Arango-Gonzalez B
影响因子：
2.5
作者：
Ghosh, KK;Bujan, S;Wässle, H
通讯作者：
Wässle, H
影响因子：
2.5
作者：
Heikkinen, H.;Vinberg, F.;Koskelainen, A.
通讯作者：
Koskelainen, A.
影响因子：
5.3
作者：
Frantseva, MV;Kokarovtseva, L;Velazquez, JLP
通讯作者：
Velazquez, JLP
影响因子：
16.2
作者：
Deans, MR;Volgyi, B;Paul, DL
通讯作者：
Paul, DL