Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That Targets Specific Cone Subtypes.
Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That Targets Specific Cone Subtypes.
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针对特定视锥细胞亚型的碎屑依赖性进行性视网膜变性的新型动物模型
DOI：
10.1167/iovs.17-22572
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发表时间：
2018-01-01
影响因子：
4.4
通讯作者：
Wei X
中科院分区：
文献类型：
--
作者：
Fu J;Nagashima M;Guo C;Raymond PA;Wei X
目的 人类 Crb1 与某些形式的视网膜变性有关，表明其在光感受器维持中发挥作用。多个 Crumbs (Crb) 极性基因在脊椎动物视网膜中表达，但其功能作用尚不清楚。为了进一步了解 Crb 和光感受器的维持，我们比较了野生型和 Tg(RH2-2:Crb2b-sfEX/RH2-2:GFP)pt108b 转基因斑马鱼之间的视网膜细胞密度，其中 Crb2b 短形式 (Crb2b-sfEX) 的胞外结构域在视网膜中作为分泌蛋白表达，破坏了 RGB 视锥细胞（红、绿、绿）的平面组织。和蓝色）通过干扰基于 Crb2a/2b 的锥体-锥体粘附。方法 我们使用标准形态测量技术来评估成年斑马鱼（3 至 27 个月大）视网膜细胞密度的年龄相关变化，并评估 Crb2b-sfEX 转基因对视网膜结构和光感受器密度的影响。使用 JB4-Feulgen 组织学测量径向切片中所有视网膜层的线性细胞密度。锥体的平面（表面）密度是在视网膜平板上测定的。将野生型和 pt108b 转基因鱼的细胞计数与“光感受器维持指数”和细胞计数的统计分析进行比较。结果野生型成年斑马鱼视网膜细胞线性密度和视锥细胞平面密度与年龄相关的变化为分析提供了基线。 Crb2b-sfEX 的表达导致 RGB 视锥细胞进行性和选择性变性，但对紫外线敏感 (UV) 视锥细胞没有影响，并增加视杆细胞的数量。结论 RGB 视锥细胞、UV 视锥细胞和视杆细胞对持续暴露于 Crb2b-sfEX 的这些不同反应表明基于 Crb 的光感受器维持机制具有高度选择性。
Purpose Human Crb1 is implicated in some forms of retinal degeneration, suggesting a role in photoreceptor maintenance. Multiple Crumbs (Crb) polarity genes are expressed in vertebrate retina, although their functional roles are not well understood. To gain further insight into Crb and photoreceptor maintenance, we compared retinal cell densities between wild-type and Tg(RH2-2:Crb2b-sfEX/RH2-2:GFP)pt108b transgenic zebrafish, in which the extracellular domain of Crb2b-short form (Crb2b-sfEX) is expressed in the retina as a secreted protein, which disrupts the planar organization of RGB cones (red, green, and blue) by interfering with Crb2a/2b-based cone-cone adhesion. Methods We used standard morphometric techniques to assess age-related changes in retinal cell densities in adult zebrafish (3 to 27 months old), and to assess effects of the Crb2b-sfEX transgene on retinal structure and photoreceptor densities. Linear cell densities were measured in all retinal layers in radial sections with JB4-Feulgen histology. Planar (surface) densities of cones were determined in retinal flat-mounts. Cell counts from wild-type and pt108b transgenic fish were compared with both a “photoreceptor maintenance index” and statistical analysis of cell counts. Results Age-related changes in retinal cell linear densities and cone photoreceptor planar densities in wild-type adult zebrafish provided a baseline for analysis. Expression of Crb2b-sfEX caused progressive and selective degeneration of RGB cones, but had no effect on ultraviolet-sensitive (UV) cones, and increased numbers of rod photoreceptors. Conclusions These differential responses of RGB cones, UV cones, and rods to sustained exposure to Crb2b-sfEX suggest that Crb-based photoreceptor maintenance mechanisms are highly selective.
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影响因子：
10.5
作者：
Meng Z;Moroishi T;Guan KL
通讯作者：
Guan KL
DOI：
10.1002/cne.22243
发表时间：
2010-03-15
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Montgomery JE;Parsons MJ;Hyde DR
通讯作者：
Hyde DR
影响因子：
4.4
作者：
Morris, AC;Schroeter, EH;Fadool, JM
通讯作者：
Fadool, JM
影响因子：
5.3
作者：
Bernardos, Rebecca L.;Barthel, Linda K.;Raymond, Pamela A.
通讯作者：
Raymond, Pamela A.
影响因子：
3.2
作者：
Fu, Jinling;Fang, Wei;Wei, Xiangyun
通讯作者：
Wei, Xiangyun