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Purinergic signaling, mediated by extracellular ATP (eATP) and P2 receptors, plays a vital role in physiological and pathological processes. The P2X7 receptor (P2X7R), a ligand-gated cation channel, is crucial in inflammation, cell death, and immune responses. Widely expressed in retinal cells, P2X7R contributes to visual function regulation and retinal degeneration. This review explores P2X7R involvement in retinal diseases, including age-related macular degeneration (AMD), Behçet's disease (BD), diabetic retinopathy (DR), glaucoma, retinitis pigmentosa (RP), uveitis, Stargardt's disease (STGD), and toxoplasmosis. P2X7R activation drives inflammation, oxidative stress, apoptosis, and immune dysregulation. For instance, it contributes to RPE degeneration in AMD, vascular proliferation in DR, neuroinflammation in glaucoma, and photoreceptor loss in RP. In uveitis, P2X7R enhances Th1 and Th17 responses. Targeting P2X7R with antagonists or modulators holds therapeutic potential, offering strategies to preserve retinal function and prevent vision loss in these debilitating diseases.
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http://dx.doi.org/10.1016/j.mam.2025.101389 | DOI Listing |
Bone
September 2025
Department of Bone and Mineral Research, Research Institute, Osaka Women's and Children's Hospital, Osaka Prefectural Hospital Organization, Izumi, Osaka, 594-1101, Japan. Electronic address:
Hypophosphatasia (HPP) is caused by inactivating variants of ALPL, the gene encoding tissue non-specific alkaline phosphatase (TNSALP). In order to deepen our understanding of the pathogenic mechanisms of HPP, we herein generated ALPL-knockout (KO) human induced pluripotent stem (iPS) cells by applying CRISPR/Cas9-mediated gene deletion to an iPS clone derived from a healthy subject. We analyzed two ALPL-KO clones, one ALPL-hetero KO clone, and a control clone isogenic except for ALPL.
View Article and Find Full Text PDFCurr Eye Res
September 2025
School of Medical Laboratory, Shandong Second Medical University, Weifang, Shandong, China.
Purpose: To study the regulatory effects and mechanisms of P2X7 receptors(P2X7R) on CD4 regulatory T cells (Tregs) and pathogenic CD4 T effector cells (Th1 cells).
Methods: In this research, an experimental autoimmune uveitis (EAU) mouse model was established to investigate the impact of P2X7R on Th1 and Treg immune responses.
Results: During the initial stage of EAU, appropriate activation of P2X7R leads to an enhanced Th1 immune response, including an increased proportion of CD4 IFN- Th1 cells, increased production of cytokines tumor necrosis factor-alpha (TNF-) and interferon-gamma (IFN-), and upregulation of transcription factor T-bet expression.
ACS Omega
August 2025
Institute of Organic Chemistry, Johannes Kepler University Linz, Altenberger Straße 69, 4040 Linz, Austria.
The P2X receptor is an emerging target for molecular imaging of inflammation in the brain and peripheral tissues. In this work, we focus on five triazole-based ligands with high affinity and selectivity for P2X receptors (, , , , and ), which are amenable to autoradiography and positron emission tomography (PET) imaging. We studied the phenomenon of conformational and rotational changes of these molecules by NMR and calculations.
View Article and Find Full Text PDFPurinergic Signal
August 2025
School of Medical Laboratory, Shandong Second Medical University, Weifang, 261053, Shandong, China.
The P2X7 receptor is a trimeric ion channel purinergic receptor. It plays a crucial part in the pathophysiology of cancers and a variety of inflammatory diseases and is widely expressed in different cell types. Leukemia represents a type of malignant clonal disorder that impacts the hematopoietic stem cells.
View Article and Find Full Text PDFToxicol In Vitro
December 2025
Postgraduate Program in Biological Sciences, Toxicological Biochemistry, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
An in vitro model using human peripheral blood mononuclear cells (PBMCs) was established to investigate the cytotoxic, oxidative and inflammatory effects and changes in purinergic system parameters caused by mercuric chloride (HgCl). Cells were exposed to concentrations of HgCl (0.05, 0.
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