ArticleMolecular neurobiology2020
Aqp9 Gene Deletion Enhances Retinal Ganglion Cell (RGC) Death and Dysfunction Induced by Optic Nerve Crush: Evidence that Aquaporin 9 Acts as an Astrocyte-to-Neuron Lactate Shuttle in Concert with Monocarboxylate Transporters To Support RGC Function and Survival.
Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Transcriptome-Based Analysis of the Mechanism of Acute Manganese-Induced Immune Function Decline and Metabolic Disorders in Estuarine Tapertail Anchovy (Animals : an open access journal from MDPI · 2026Article
- Anti-IL-6 Receptor Antibody Suppresses Visual Dysfunction in AQP4 Peptide-Immunized Mice.Translational vision science & technology · 2026Article
- Next-Gen Neuroprotection in Glaucoma: Synergistic Molecules for Targeted Therapy.Journal of clinical medicine · 2025Review
- Aquaporins in Acute Brain Injury: Insights from Clinical and Experimental Studies.Biomedicines · 2025Review
- Aquaporin-4 Peptide Injection in Mice Induces Retinal and Optic Nerve Alterations That Simulate Those of Neuromyelitis Optica Spectrum Disorder.Translational vision science & technology · 2025Article
- Article
- Role of aquaporins in brain water transport and edema.Frontiers in neuroscience · 2025Review
- Exploring Aquaporins in Human Studies: Mechanisms and Therapeutic Potential in Critical Illness.Life (Basel, Switzerland) · 2024Review
- Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.International journal of molecular sciences · 2024Review
- Potentially compromised systemic and local lactate metabolic balance in glaucoma, which could increase retinal glucose and glutamate concentrations.Scientific reports · 2024Article
- Aquaporins in Eye.Advances in experimental medicine and biology · 2023Article
- Aquaporins in Cardiovascular System.Advances in experimental medicine and biology · 2023Article
- Unlocking the role of lactate: metabolic pathways, signaling, and gene regulation in postmitotic retinal cells.Frontiers in ophthalmology · 2023Review
- Honey, I shrunk the extracellular space: Measurements and mechanisms of astrocyte swelling.Glia · 2022Review
- Insight into the Mammalian Aquaporin Interactome.International journal of molecular sciences · 2022Review
- Signaling Mechanisms and Pharmacological Modulators Governing Diverse Aquaporin Functions in Human Health and Disease.International journal of molecular sciences · 2022Review
- Lactic Acid Permeability of Aquaporin-9 Enables Cytoplasmic Lactate Accumulation via an Ion Trap.Life (Basel, Switzerland) · 2022Article
- Proteomic and metabolomic profiling of acupuncture for migraine reveals a correlative link via energy metabolism.Frontiers in neuroscience · 2022Article
- Adaptive responses to neurodegenerative stress in glaucoma.Progress in retinal and eye research · 2021Review
- Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas.Antioxidants (Basel, Switzerland) · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aquaporin 9 (AQP9) is an aquaglyceroporin that can transport lactate. Accumulating evidence suggests that astrocyte-to-neuron lactate shuttle (ANLS) plays a critical role in energy metabolism in neurons, including retinal ganglion cells (RGCs). To test the hypothesis that AQP9, in concert with monocarboxylate transporters (MCTs), participates in ANLS to maintain function and survival of RGCs, Aqp9-null mice and wild-type (WT) littermates were subjected to optic nerve crush (ONC) with or without intravitreal injection of an MCT2 inhibitor. RGC density was similar between the Aqp9-null mice and WT mice without ONC, while ONC resulted in significantly more RGC density reduction in the Aqp9-null mice than in the WT mice at day 7. Positive scotopic threshold response (pSTR) amplitude values were similar between the two groups without ONC, but were significantly more reduced in the Aqp9-null mice than in the WT mice 7days after ONC. MCT2 inhibitor injection accelerated RGC death and pSTR amplitude reduction only in the WT mice with ONC. Immunolabeling revealed that both RGCs and astrocytes expressed AQP9, that ONC predominantly reduced astrocytic AQP9 expression, and that MCTs 1, 2, and 4 were co-localized with AQP9 at the ganglion cell layer. These retinal MCTs were also co-immunoprecipitated with AQP9 in the WT mice. ONC decreased the co-immunoprecipitation of MCTs 1 and 4, but did not impact co-immunoprecipitation of MCT2. Retinal glucose transporter 1 expression was increased in Aqp9-null mice. Aqp9 gene deletion reduced and increased the intraretinal L-lactate and D-glucose concentrations, respectively. Results suggest that AQP9 acts as the ANLS to maintain function and survival of RGCs.
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