Dynamics of Cyclooxygenase-1 Positive Microglia/Macrophage in the Retina of Pathological Model Mice as a Biomarker of the Retinal Inflammatory Diseases.
In an intraocular inflammatory state, microglia residing in the retina become active and migrate inside the retina. In this study, we investigated whether cyclooxygenase-1 (COX-1) expressed by retinal microglia/macrophage can be a biomarker for the diagnosis of retinal diseases. COX-1 was immunopositive in microglia/macrophage and neutrophils, while COX-2 was immunopositive in astrocytes and neurons in the inner layer of normal retina. The number of COX-1 positive cells per section of the retinal tissue was 14 ± 2.8 (mean ± standard deviation) in normal mice, which showed significant increase in the lipopolysaccharide (LPS)-administrated model (62 ± 5.0, p = 8.7 × 10−9). In addition to microglia, we found neutrophils that were positive for COX-1. In the early stage of inflammation in the experimental autoimmune uveoretinitis (EAU), COX-1 positive cells, infiltrating from the ciliary body into the retinal outer nuclear layer, were observed. The number of infiltrating COX-1 positive cells correlated with the severity of EAU. Taken together, the increased number of COX-1 positive microglia/macrophage with morphological changes were observed in the retinas of retinal inflammatory disease models. This suggests that COX-1 can be a marker of disease-related activities of microglia/macrophage, which should be useful for the diagnosis of retinal diseases.
Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-gr...
Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (iPSC-RPE) cells in patients with age-related macular degeneration. However, there was an issue regarding immune rejection after transplantation. In this study, we established a preoperational in vitro “drug–lymphocytes–grafts immune reaction (Drug-LGIR)” test to determine the medication for immune rejection using...
Microglia originate from yolk sac-primitive macrophages and auto-proliferate into adulthood without replacement by bone marrow-derived circulating cells. In inflammation, stroke, aging, or infection, microglia have been shown to contribute to brain pathology in both deleterious and beneficial ways, which have been studied extensively. However, less is known about their role in the healthy adult brain. Astrocytes and oligodendrocytes are widely accepted to strongly contribute to the maintenance o...
Abstract Biomarkers of specific targets are becoming an essential objective for clinical unmet clinical needs to improve diseases early detection and increase patient overall survival. Ovarian cancer is among the highest mortality gynecological cancers. It is asymptomatic and almost always diagnosed at advanced stage. At five years from the first diagnosis the survival rate of ovarian cancer patients is only 30%. Cyclooxygenase (COX)-1 as opposed to COX-2 is known to be overexpressed in ovarian ...
#1Zhaohui Yuan(SYSU: Sun Yat-sen University)H-Index: 1
#2Xiaoyun Chen(SYSU: Sun Yat-sen University)H-Index: 1
Last. Yizhi Liu(SYSU: Sun Yat-sen University)H-Index: 32
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Purpose: Uveitis is a serious inflammatory disease of the uvea, frequently leading to visual impairment and irreversible blindness. Here, we investigated the anti-inflammatory effect of minocycline on rat endotoxin-induced uveitis (EIU) and retinal inflammation. Methods: For in vivo studies, the rat EIU model was induced with intravitreal injection of lipopolysaccharide (LPS). Minocycline was administered intraperitoneally 2 h before and after the LPS injection. The severity of the ocular inflam...
Abstract Dopamine D 2 receptors (D 2 R) are expressed in the human retina and play an important role in the modulation of neural responses to light-adaptation. However, it is unknown whether dopamine D 3 receptors (D 3 R) are expressed in the human retina. Using positron emission tomography (PET), we have observed significant uptake of the D 3 R-preferring agonist radiotracer [ 11 C]-(+)-PHNO into the retina of humans in vivo . This led us to examine whether [ 11 C]-(+)-PHNO binding in the retin...
#1Qi Zhang(CPU: China Pharmaceutical University)H-Index: 10
#2Zhihao Han(CPU: China Pharmaceutical University)H-Index: 8
Last. Yueqing Gu(CPU: China Pharmaceutical University)H-Index: 31
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: Targeting cyclooxygenase-2 (COX-2) for molecular imaging is an attractive approach applicable for its overexpression in inflammation and many malignancies. Herein, for monitoring COX-2, we synthesize a specific COX-2 probe celecoxib-MPA probe (CMP), based on celecoxib and a water-soluble near-infrared dye dye ICG-Der-02 (MPA). Its high affinity for binding to COX-2 is verified by molecular docking, dynamics simulation and inhibition assay. At cellular level, CMP selectively accumulates in cyto...
#1Stal Shrestha(NIH: National Institutes of Health)H-Index: 6
#2Prachi Singh(NIH: National Institutes of Health)H-Index: 4
Last. Victor W. Pike(NIH: National Institutes of Health)H-Index: 64
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In our preceding paper (Part 1), we identified three 1,5-bis-diaryl-1,2,4-triazole-based compounds that merited evaluation as potential positron emission tomography (PET) radioligands for selectively imaging cyclooxygenase-1 (COX-1) in monkey and human brain, namely, 1,5-bis(4-methoxyphenyl)-3-(alkoxy)-1H-1,2,4-triazoles bearing a 3-methoxy (PS1), a 3-(2,2,2-trifluoroethoxy) (PS13), or a 3-fluoromethoxy substituent (PS2). PS1 and PS13 were labeled from phenol precursors by O-11C-methylation with...
#1Prachi Singh(NIH: National Institutes of Health)H-Index: 4
#1Prachi Singh(NIH: National Institutes of Health)H-Index: 3
Last. Victor W. Pike(NIH: National Institutes of Health)H-Index: 64
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Cyclooxygenase-1 (COX-1) is a key enzyme in the biosynthesis of proinflammatory thromboxanes and prostaglandins and is found in glial and neuronal cells within brain. COX-1 expression is implicated in numerous neuroinflammatory states. We aim to find a direct-acting positron emission tomography (PET) radioligand for imaging COX-1 in human brain as a potential biomarker of neuroinflammation and for serving as a tool in drug development. Seventeen 3-substituted 1,5-diaryl-1H-1,2,4-triazoles were p...