ArticleInvestigative ophthalmology & visual science2022
Spleen Tyrosine Kinase Contributes to Müller Glial Expression of Proangiogenic Cytokines in Diabetes.
Article in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- GSK3β promotes p53/Nrf2-dependent expression of the stress response protein REDD2 in retinal Müller glia exposed to hyperlipidemic conditions.Experimental eye research · 2026Article
- Article
- TREM2 in age-related macular degeneration: a microglia-centered perspective in the retinal myeloid landscape.Frontiers in ophthalmology · 2026Review
- PU.1 dictates β-amyloid-induced TREM2 expression upregulation in microglia in a transgenic model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- Retinal transcriptome profiling identifies novel candidate genes associated with visual impairment in a mouse model of multiple sclerosis.Animal cells and systems · 2023Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: Neuroglial dysfunction occurs early in the progression of diabetic retinopathy. In response to diabetes or hypoxia, Müller glia secrete cytokines and growth factors that contribute to disease progression. This study was designed to examine common signaling pathways activated in Müller glia by both type 1 and pre-/type 2 diabetes. Methods: RiboTag (Pdgfra-cre;HA-Rpl22) mice were used to compare the impact of streptozotocin (STZ) and a high-fat, high-sucrose (HFHS) diet on ribosome association of mRNAs in Müller glia by RNA sequencing analysis. Human MIO-M1 Müller cells were exposed to either hyperglycemic or hypoxic culture conditions. Genetic manipulation and pharmacologic inhibition were used to interrogate signaling pathways. Results: Association of mRNAs encoding triggering receptor expressed on myeloid cells 2 (TREM2), DNAX-activating protein 12 kDa (DAP12), and colony stimulating factor 1 receptor (CSF1R) with ribosomes isolated from Müller glia was upregulated in both STZ diabetic mice and mice fed an HFHS diet. The TREM2/DAP12 receptor-adaptor complex signals in coordination with CSF1R to activate spleen tyrosine kinase (SYK). SYK activation was enhanced in the retina of diabetic mice and in human MIO-M1 Müller cell cultures exposed to hyperglycemic or hypoxic culture conditions. DAP12 knockdown reduced SYK autophosphorylation in Müller cells exposed to hyperglycemic or hypoxic conditions. SYK inhibition or DAP12 knockdown suppressed hypoxia-induced expression of the transcription factor hypoxia-inducible factor 1⍺ (HIF1⍺), as well as expression of vascular endothelial growth factor and angiopoietin-like 4. Conclusions: The findings support TREM2/DAP12 receptor-adaptor complex signaling via SYK to promote HIF1α stabilization and increased angiogenic cytokine production by Müller glia.
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