Marion Haug, Sara A Haddad-Velioglu, Manuela Berger, Anja Enz, Jingjing Zang, Stephan C F Neuhauss
{"title":"斑马鱼视网膜中 mGluR6 Paralogs 的不同定位和功能作用","authors":"Marion Haug, Sara A Haddad-Velioglu, Manuela Berger, Anja Enz, Jingjing Zang, Stephan C F Neuhauss","doi":"10.1167/iovs.65.12.44","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To define the location of mglur6 paralogs in the outer zebrafish retina and delineate their contribution to retina light responses across the visual spectrum.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"44"},"PeriodicalIF":5.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536201/pdf/","citationCount":"0","resultStr":"{\"title\":\"Differential Localization and Functional Roles of mGluR6 Paralogs in Zebrafish Retina.\",\"authors\":\"Marion Haug, Sara A Haddad-Velioglu, Manuela Berger, Anja Enz, Jingjing Zang, Stephan C F Neuhauss\",\"doi\":\"10.1167/iovs.65.12.44\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To define the location of mglur6 paralogs in the outer zebrafish retina and delineate their contribution to retina light responses across the visual spectrum.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":14620,\"journal\":{\"name\":\"Investigative ophthalmology & visual science\",\"volume\":\"65 12\",\"pages\":\"44\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536201/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Investigative ophthalmology & visual science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1167/iovs.65.12.44\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Investigative ophthalmology & visual science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1167/iovs.65.12.44","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
Differential Localization and Functional Roles of mGluR6 Paralogs in Zebrafish Retina.
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.
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.