ArticleExperimental eye research2022
Expression and activation of the ketone body receptor HCAR2/GPR109A promotes preservation of retinal endothelial cell barrier function.
Article in Experimental eye research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- The microbiota-gut-brain-epigenome axis as a novel therapeutic target for decoding postpartum depression.Frontiers in medicine · 2026Pooled it
- Short-Chain Fatty Acids: Microbial Metabolites Driving Gut-Eye Axis Signaling.Comprehensive physiology · 2026Review
- Ketone Ester Attenuates Thoracic Aortic Aneurysm and Dissection by Suppressing Ferroptosis.Cells · 2026Article
- GPR109a-AMPK axis mediates the Attenuation of uric acid-induced M1 macrophage polarization by β-hydroxybutyrate from Lacticaseibacillus rhamnosus M2b.Scientific reports · 2026Article
- Review
- The multifaceted roles of ketones in physiology.Experimental physiology · 2026Review
- Hydroxycarboxylic acid receptor 2 (GPR109A) and retinopathies: pathways and prospects.Frontiers in medicine · 2026Review
- BDH1-Dependent Ketone Body Metabolism Maintains Müller Cell Homeostasis and Retinal Function.bioRxiv : the preprint server for biology · 2025Article
- HCAR2 is a novel receptor for heme.Blood advances · 2025Article
- Natural remedies proposed for the management of diabetic retinopathy (DR): diabetic complications.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Gut-Brain Axis: Role of Microbiome, Metabolomics, Hormones, and Stress in Mental Health Disorders.Cells · 2024Review
- The Role of Probiotics and Their Metabolites in the Treatment of Depression.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Preservation of retinal barrier function is critical to maintenance of retinal health. Therefore, it is not surprising that loss of barrier integrity is a pathologic feature common to degenerative retinal diseases such as diabetic retinopathy. Our prior studies demonstrate the importance of hydroxycarboxylic acid receptor 2/GPR109A (HCAR2/GPR109A) expression in the retinal pigment epithelium (RPE) to outer retinal barrier integrity. However, whether HCAR2/GPR109A is expressed in retinal endothelial cells and has a similar relationship to inner blood retinal barrier regulation is not known. In the current study, we examined relevance of receptor expression to endothelial cell dependent-blood retinal barrier integrity. siRNA technology was used to modulate HCAR2/GPR109A expression in human retinal endothelial cells (HRECs). Cells were cultured in the presence or absence of VEGF, a pro-inflammatory stimulus, and/or various concentrations of the HCAR2/GPR109A-specific agonist beta-hydyroxybutyrate (BHB). HCAR2/GPR109A expression was monitored by qPCR and electrical cell impedance sensing (ECIS) was used to evaluate barrier function. Complementary in vivo studies were conducted in wildtype and HCAR2/GPR109A knockout mice treated intraperitoneally with lipopolysaccharide and/or BHB. Vascular leakage was monitored using fluorescein angiography and Western blot analyses of albumin extravasation. Additionally, retinal function was evaluated by OptoMotry. Decreased (siRNA knockdown) or absent (gene knockout) HCAR2/GPR109A expression was associated with impaired barrier function both in vitro and in vivo. BHB treatment provided some protection, limiting disruptions in retinal barrier integrity and function; an effect that was found to be receptor (HCAR2/GPR109A)-dependent. Collectively, the present studies support a key role for HCAR2/GPR109A in regulating blood-retinal barrier integrity and highlight the therapeutic potential of the receptor toward preventing and treating retinal diseases such as diabetic retinopathy in which compromised barrier function is paramount.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.