Differential Localization and Functional Roles of mGluR6 Paralogs in Zebrafish Retina.

IF 5 2区 医学 Q1 OPHTHALMOLOGY
Marion Haug, Sara A Haddad-Velioglu, Manuela Berger, Anja Enz, Jingjing Zang, Stephan C F Neuhauss
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引用次数: 0

Abstract

Purpose: To define the location of mglur6 paralogs in the outer zebrafish retina and delineate their contribution to retina light responses across the visual spectrum.

Methods: In situ hybridization and immunolocalization with custom-made antibodies were used to localize mglur6 transcripts, proteins, and additional components of the mGluR6 signaling complex. Gene editing was used to generate knockout mutants that were analyzed with white light and spectral electroretinography.

Results: Both mglur6 paralogs colocalized with known downstream pathway genes, such as trpm1a, nyctalopin, and gnaoβ. All rod photoreceptors contacted mGluR6-positive cells, while cone connectivity presented a more complex situation with no red cones and only a few UV and blue-sensitive cones connecting to mGluR6a-positive bipolar cells. All cone subtypes contacted mGluR6b-positive cells with markedly fewer red-sensitive cones. Retinas of knockout animals displayed no morphologic alterations. While ERG responses were unaffected in mglur6a knockout animals, mglur6b mutants displayed decreased responses over all spectral wavelengths.

Conclusions: We demonstrated that mGlurR6 signalplex components are similar in the zebrafish and the mammalian retina. Despite mglur6b knockout animals having significantly impaired ERG b-wave responses, a residual b-wave persists, even in double knockouts, suggesting additional pathway components yet to be identified.

斑马鱼视网膜中 mGluR6 Paralogs 的不同定位和功能作用
目的:确定mglur6旁系亲属在斑马鱼视网膜外层的位置,并划定它们在整个视觉光谱中对视网膜光反应的贡献:方法:利用原位杂交和定制抗体的免疫定位来定位mglur6转录本、蛋白质和mGluR6信号复合体的其他成分。利用基因编辑技术产生基因敲除突变体,并用白光和光谱视网膜电图对其进行分析:结果:两个mglur6旁系基因都与已知的下游通路基因(如trpm1a、nyctalopin和gnaoβ)共定位。所有杆状光感受器都与 mGluR6 阳性的细胞相连,而锥体的连接情况更为复杂,没有红色锥体,只有少数紫外线和蓝色敏感锥体与 mGluR6a 阳性的双极细胞相连。所有视锥亚型都与 mGluR6b 阳性细胞相连,但红色敏感视锥明显较少。基因敲除动物的视网膜无形态学改变。mglur6a基因敲除动物的ERG反应不受影响,而mglur6b突变体在所有光谱波长上的反应都有所下降:结论:我们证明了mGlurR6信号复合体成分在斑马鱼和哺乳动物视网膜中的相似性。尽管mglur6b基因敲除动物的ERG b波反应明显受损,但即使在双基因敲除动物中,残余的b波仍然存在,这表明还有其他通路成分有待鉴定。
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来源期刊
CiteScore
6.90
自引率
4.50%
发文量
339
审稿时长
1 months
期刊介绍: Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.
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