A Comprehensive Study of c-Kit–Expressing Amacrine Cells in the Mammalian Retina

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Abstract Amacrine cells assemble complex circuits in the inner retina, where they integrate, modulate, and relay spatial and temporal information to retinal ganglion cells. Nevertheless, their organization and functional diversity are still not fully understood. In this study, we identify a distinct group of amacrine cells that express the stem cell factor receptor-c-Kit. Using combined techniques of anti-CD117 (c-Kit) immunolabeling, confocal imaging, and computational algorithms, we characterize the morphological features and spatial distribution of the c-Kit–expressing amacrine cells. Our results show that c-Kit-expressing amacrine cells are GABA-positive neurons with medium to wide dendritic fields that stratify within the specific strata in both ON and OFF sublaminae of the inner plexiform layer (IPL). The density recovery profile of c-Kit cells reveals regulated intercellular spacing, supporting the notion that they represent a single amacrine subtype with significant variation in their dendritic structures. Notably, a subset of these cells also bears ascending processes projecting into the outer plexiform layer (OPL). This distinct anatomical feature raises the possibility that c-Kit-expressing amacrine cells contribute to a long-range circuit across retinal layers and participate in a novel feedback pathway. Further analysis demonstrates that c-Kit–expressing amacrine cells are distinct from AII, starburst, nGnG, vGluT3-positive, VIP-positive, and dopaminergic amacrine cells. Our findings provide a new insight into the cellular diversity of amacrine cells and suggest a previously unrecognized functional role for c-Kit–expressing amacrine cells in the mammalian retina.
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A Comprehensive Study of c-Kit–Expressing Amacrine Cells in the Mammalian Retina | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A Comprehensive Study of c-Kit–Expressing Amacrine Cells in the Mammalian Retina Zheng Jiang, Wen Shen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7510969/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted 12 You are reading this latest preprint version Abstract Amacrine cells assemble complex circuits in the inner retina, where they integrate, modulate, and relay spatial and temporal information to retinal ganglion cells. Nevertheless, their organization and functional diversity are still not fully understood. In this study, we identify a distinct group of amacrine cells that express the stem cell factor receptor-c-Kit. Using combined techniques of anti-CD117 (c-Kit) immunolabeling, confocal imaging, and computational algorithms, we characterize the morphological features and spatial distribution of the c-Kit–expressing amacrine cells. Our results show that c-Kit-expressing amacrine cells are GABA-positive neurons with medium to wide dendritic fields that stratify within the specific strata in both ON and OFF sublaminae of the inner plexiform layer (IPL). The density recovery profile of c-Kit cells reveals regulated intercellular spacing, supporting the notion that they represent a single amacrine subtype with significant variation in their dendritic structures. Notably, a subset of these cells also bears ascending processes projecting into the outer plexiform layer (OPL). This distinct anatomical feature raises the possibility that c-Kit-expressing amacrine cells contribute to a long-range circuit across retinal layers and participate in a novel feedback pathway. Further analysis demonstrates that c-Kit–expressing amacrine cells are distinct from AII, starburst, nGnG, vGluT3-positive, VIP-positive, and dopaminergic amacrine cells. Our findings provide a new insight into the cellular diversity of amacrine cells and suggest a previously unrecognized functional role for c-Kit–expressing amacrine cells in the mammalian retina. Biological sciences/Cell biology Biological sciences/Neuroscience Amacrine cells c-Kit/CD117 somatic mosaics density recovery profile mouse retina Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 05 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 17 Oct, 2025 Reviews received at journal 08 Oct, 2025 Reviews received at journal 04 Oct, 2025 Reviews received at journal 02 Oct, 2025 Reviewers agreed at journal 28 Sep, 2025 Reviewers agreed at journal 27 Sep, 2025 Reviewers agreed at journal 24 Sep, 2025 Reviewers invited by journal 22 Sep, 2025 Editor assigned by journal 22 Sep, 2025 Editor invited by journal 16 Sep, 2025 Submission checks completed at journal 11 Sep, 2025 First submitted to journal 11 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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