{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have established that precise signal transmission in the retina depends on an intricate cascade initiated by metabotropic glutamate receptor 6 (mGluR6) on ON bipolar cells. mGluR6 activation modulates downstream effectors—including the nonselective cation channel TRPM1 and heterotrimeric G‐proteins—to convert photoreceptor‐generated signals into appropriate bipolar cell responses. Mutations and splicing errors in Grm6, the gene encoding mGluR6, disrupt this pathway and result in phenotypes such as congenital stationary night blindness, as documented by multiple investigations (see, for example."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther complementary studies have delved into the mechanisms governing synaptic organization and protein trafficking at the photoreceptor-to-ON bipolar cell synapse. These works highlight the importance of precise protein targeting, including the roles of post-translational modifications (e.g. complex N-glycosylation of mGluR6) and trans-synaptic interactions with adhesion molecules like ELFN proteins, which are essential for consolidating the mGluR6 macromolecular complex and ensuring proper channel localization. Moreover, such defects in synaptic assembly and dendritic invagination have been correlated with disrupted visual processing, as observed in diverse models and allelic variants (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to these retinal studies, some related research has explored distinct physiological systems—such as the genetic determinants of obesity and the modulation of inflammatory responses following cerebral ischemia—which, while addressing different organ systems"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", underscore the broad relevance of molecular regulation in both neuronal and systemic contexts. A separate clinical report also describes overlapping retinal pathologies wherein mutations in GRM6 co-occur with other retinal dystrophies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNotably, however, none of the provided abstracts explicitly mention or investigate MIR6837. Given the extensive focus on the molecular components of retinal neurotransmission—particularly the roles of mGluR6, its regulators, and associated signaling partners—a plausible hypothesis is that MIR6837, if expressed in the relevant retinal cells, may function as a post‐transcriptional regulator of key components within this signaling network. Its potential role could involve modulating the expression or trafficking of proteins central to ON bipolar cell function, thereby influencing synaptic architecture and visual signal processing. Future studies will be required to directly test this hypothesis and delineate the specific targets and mechanistic actions of MIR6837 in these pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chieko Koike, Takehisa Obara, Yoshitsugu Uriu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0912730107"}], "href": "https://doi.org/10.1073/pnas.0912730107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19966281"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19966281"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dennis M Maddox, Kirstan A Vessey, Gary L Yarbrough, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vis Neurosci (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S0952523807070149"}], "href": "https://doi.org/10.1017/S0952523807070149"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17430614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17430614"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "René C Rentería, Ning Tian, Jianhua Cang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intrinsic ON responses of the retinal OFF pathway are suppressed by the ON pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.1718-06.2006"}], "href": "https://doi.org/10.1523/JNEUROSCI.1718-06.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17108159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17108159"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ying Xu, Anuradha Dhingra, Marie E Fina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "mGluR6 deletion renders the TRPM1 channel in retina inactive."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurophysiol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/jn.00933.2011"}], "href": "https://doi.org/10.1152/jn.00933.2011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22131384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22131384"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Salma Quraishi, Jacqueline Gayet, Catherine W Morgans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distribution of group-III metabotropic glutamate receptors in the retina."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Comp Neurol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cne.21274"}], "href": "https://doi.org/10.1002/cne.21274"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17311335"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17311335"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shanti R Tummala, Adam Neinstein, Marie E Fina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Localization of Cacna1s to ON bipolar dendritic tips requires mGluR6-related cascade elements."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.13-13766"}], "href": "https://doi.org/10.1167/iovs.13-13766"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24519419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24519419"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Haohua Qian, Rui Ji, Ronald G Gregg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a new mutant allele, Grm6(nob7), for complete congenital stationary night blindness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vis Neurosci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S0952523815000012"}], "href": "https://doi.org/10.1017/S0952523815000012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26241901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26241901"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yoshihiko Tsukamoto, Naoko Omi "}, {"type": "b", "children": [{"type": "t", "text": "Effects of mGluR6-deficiency on photoreceptor ribbon synapse formation: comparison of electron microscopic analysis of serial sections with random sections."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vis Neurosci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S0952523813000473"}], "href": "https://doi.org/10.1017/S0952523813000473"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24801622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24801622"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Shanti R Tummala, Anuradha Dhingra, Marie E Fina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of mGluR6-related cascade elements leads to retrograde trans-synaptic effects on rod photoreceptor synapses via matrix-associated proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Neurosci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/ejn.13243"}], "href": "https://doi.org/10.1111/ejn.13243"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27037829"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27037829"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Neal S Peachey, Nazarul Hasan, Bernard FitzMaurice, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A missense mutation in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Grm6"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " reduces but does not eliminate mGluR6 expression or rod depolarizing bipolar cell function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurophysiol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/jn.00888.2016"}], "href": "https://doi.org/10.1152/jn.00888.2016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28490646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28490646"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Melina A Agosto, Abiodun Adefola R Adeosun, Nitin Kumar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mGluR6 ligand-binding domain, but not the C-terminal domain, is required for synaptic localization in retinal ON-bipolar cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2021.101418"}], "href": "https://doi.org/10.1016/j.jbc.2021.101418"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34793838"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34793838"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Junzo Kinoshita, Nazarul Hasan, Brent A Bell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced expression of the "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "nob8"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " gene does not normalize the distribution or function of mGluR6 in the mouse retina."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Vis (2019)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32025181"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32025181"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Michael L Miller, Mustansir Pindwarawala, Melina A Agosto "}, {"type": "b", "children": [{"type": "t", "text": "Complex N-glycosylation of mGluR6 is required for trans-synaptic interaction with ELFN adhesion proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2024.107119"}], "href": "https://doi.org/10.1016/j.jbc.2024.107119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38428819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38428819"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Heike Vogel, Matthias Nestler, Franz Rüschendorf, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of Nob3, a major quantitative trait locus for obesity and hyperglycemia on mouse chromosome 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Physiol Genomics (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/physiolgenomics.00011.2009"}], "href": "https://doi.org/10.1152/physiolgenomics.00011.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19470805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19470805"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Jennifer E Kim, Ryan P Lee, Eli Yazigi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Behav Immun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbi.2023.12.007"}], "href": "https://doi.org/10.1016/j.bbi.2023.12.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38070624"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38070624"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Nancy Huynh, Brett G Jeffrey, Amy Turriff, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sorting out co-occurrence of rare monogenic retinopathies: Stargardt disease co-existing with congenital stationary night blindness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ophthalmic Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/13816810.2013.865762"}], "href": "https://doi.org/10.3109/13816810.2013.865762"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24397708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24397708"}]}]}]}