ArticleThe American journal of pathology2018
Inhibition of Atypical Protein Kinase C Reduces Inflammation-Induced Retinal Vascular Permeability.
Article in The American journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Hyperosmolar stress induces monocyte chemoattractant protein 1 expression in retinal pigmented epithelial arising retinal pigmented epithelial 19 cells.Molecular vision · 2025Article
- Trimethylamine N-oxide aggravates vascular permeability and endothelial cell dysfunction under diabetic condition:International journal of ophthalmology · 2024Article
- Correlation between diabetic retinopathy and diabetic nephropathy: a two-sample Mendelian randomization study.Frontiers in endocrinology · 2023Article
- Reducing Akt2 in retinal pigment epithelial cells causes a compensatory increase in Akt1 and attenuates diabetic retinopathy.Nature communications · 2022Article
- Fatty Acid-Binding Protein 4 in Patients with and without Diabetic Retinopathy.Diabetes & metabolism journal · 2022Article
- Pigment Epithelium-Derived Factor Protects Retinal Neural Cells and Prevents Pathological Angiogenesis in anOxidative medicine and cellular longevity · 2022Article
- Current understanding of the molecular and cellular pathology of diabetic retinopathy.Nature reviews. Endocrinology · 2021Review
- Early alterations of neurovascular unit in the retina in mouse models of tauopathy.Acta neuropathologica communications · 2021Article
- Inactivation of Endothelial ADAM17 Reduces Retinal Ischemia-Reperfusion Induced Neuronal and Vascular Damage.International journal of molecular sciences · 2020Article
- All-trans-Retinaldehyde Contributes to Retinal Vascular Permeability in Ischemia Reperfusion.Investigative ophthalmology & visual science · 2020Article
- Synthesis and structure-activity relationships of thieno[2,3-d]pyrimidines as atypical protein kinase C inhibitors to control retinal vascular permeability and cytokine-induced edema.Bioorganic & medicinal chemistry · 2020Article
- Podosome formation impairs endothelial barrier function by sequestering zonula occludens proteins.Journal of cellular physiology · 2020Article
- Norrin restores blood-retinal barrier properties after vascular endothelial growth factor-induced permeability.The Journal of biological chemistry · 2020Article
- Electrotonic transmission in the retinal vasculature: inhibitory role of the diabetes/VEGF/aPKC pathway.Physiological reports · 2019Article
- Diabetic Retinopathy-An Underdiagnosed and Undertreated Inflammatory, Neuro-Vascular Complication of Diabetes.Frontiers in endocrinology · 2019Article
- Atypical Protein Kinase C: Breaking Down Barriers in Ocular Disease?The American journal of pathology · 2018Article
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7 authors at 3 institutions in 1 country.
Funding
Abstract
Changes in permeability of retinal blood vessels contribute to macular edema and the pathophysiology of numerous ocular diseases, including diabetic retinopathy, retinal vein occlusions, and macular degeneration. Vascular endothelial growth factor (VEGF) induces retinal permeability and macular thickening in these diseases. However, inflammatory agents, such as tumor necrosis factor-α (TNF-α), also may drive vascular permeability, specifically in patients unresponsive to anti-VEGF therapy. Recent evidence suggests VEGF and TNF-α induce permeability through distinct mechanisms; however, both require the activation of atypical protein kinase C (aPKC). We provide evidence, using genetic mouse models and therapeutic intervention with small molecules, that inhibition of aPKC prevented or reduced vascular permeability in animal models of retinal inflammation. Expression of a kinase-dead aPKC transgene, driven by a vascular and hematopoietic restricted promoter, reduced retinal vascular permeability in an ischemia-reperfusion model of retinal injury. This effect was recapitulated with a small-molecule inhibitor of aPKC. Expression of the kinase-dead aPKC transgene dramatically reduced the expression of inflammatory factors and blocked the attraction of inflammatory monocytes and granulocytes after ischemic injury. Coinjection of VEGF with TNF-α was sufficient to induce permeability, edema, and retinal inflammation, and treatment with an aPKC inhibitor prevented VEGF/TNF-α-induced permeability. These data suggest that aPKC contributes to inflammation-driven retinal vascular pathology and may be an attractive target for therapeutic intervention.
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