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Article ; Online: A MEK inhibitor arrests the cell cycle of human conjunctival fibroblasts and improves the outcome of glaucoma filtration surgery.

Lee, Jinhee / Honjo, Megumi / Aihara, Makoto

2024 Volume 14, Issue 1, Page(s) 1871

Abstract: Better agents are needed to improve glaucoma filtration surgery outcomes compared to current ones. The purpose of this study is to determine whether mitogen-activated protein kinase kinase (MEK) inhibitors can effectively arrest the cell cycle of human ... ...

Abstract	Better agents are needed to improve glaucoma filtration surgery outcomes compared to current ones. The purpose of this study is to determine whether mitogen-activated protein kinase kinase (MEK) inhibitors can effectively arrest the cell cycle of human conjunctival fibroblasts (HCFs) and inhibit the formation of fibrosis and scarring following glaucoma filtration surgery. A cell counting kit‑8 assay revealed that the MEK inhibitor PD0325901 exhibited concentration-dependent growth inhibition of HCFs. Quantitative PCR, immunocytochemistry, and western blotting demonstrated decreased expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 and increased expression of p27 in HCFs treated with PD0325901. Flow cytometry indicated that PD0325901 arrested the cell cycle of HCFs in the G0/1 phase. The cell-migration assay showed that HCF migration rate was significantly suppressed by PD0325901 exposure. Rabbits were divided into PD0325901-treatment and control groups, and glaucoma filtration surgery was performed. Although intraocular pressure did not differ between PD0325901-treatment and control groups, bleb height was greater in the treatment group. Histopathological evaluation revealed that fibrotic changes were significantly attenuated in the PD0325901-treatment group compared to the control group. In conclusion, the MEK inhibitor impedes HCF proliferation via cell-cycle arrest and may be beneficial for glaucoma filtration surgery by reducing bleb scarring.
MeSH term(s)	Animals ; Humans ; Rabbits ; Cicatrix/drug therapy ; Cicatrix/prevention & control ; Cell Cycle ; Filtering Surgery ; Glaucoma/surgery ; Protein Kinase Inhibitors/pharmacology ; Benzamides ; Diphenylamine/analogs & derivatives
Chemical Substances	mirdametinib (86K0J5AK6M) ; Protein Kinase Inhibitors ; Benzamides ; Diphenylamine (9N3CBB0BIQ)
Language	English
Publishing date	2024-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-52359-y
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Article ; Online: An Autotaxin-Induced Ocular Hypertension Mouse Model Reflecting Physiological Aqueous Biomarker.

Shimizu, Shota / Honjo, Megumi / Liu, Mengxuan / Aihara, Makoto

Investigative ophthalmology & visual science

2024 Volume 65, Issue 2, Page(s) 32

Abstract: Purpose: Animal models of ocular hypertension (OH) have been developed to understand the pathogenesis of glaucoma and facilitate drug discovery. However, many of these models are fraught with issues, including severe intraocular inflammation and ... ...

Abstract	Purpose: Animal models of ocular hypertension (OH) have been developed to understand the pathogenesis of glaucoma and facilitate drug discovery. However, many of these models are fraught with issues, including severe intraocular inflammation and technical challenges. Lysophosphatidic acid (LPA) is implicated in trabecular meshwork fibrosis and increased resistance of aqueous outflow, factors that contribute to high intraocular pressure (IOP) in human open-angle glaucoma. We aimed to elevate IOP by increasing expression of the LPA-producing enzyme autotaxin (ATX) in mouse eyes. Methods: Tamoxifen-inducible ATX transgenic mice were developed. Tamoxifen was administered to six- to eight-week-old mice via eye drops to achieve ATX overexpression in the eye. IOP and retinal thickness were measured over time, and retinal flat-mount were evaluated to count retinal ganglion cells (RGCs) loss after three months. Results: Persistent elevation of ATX expression in mouse eyes was confirmed through immunohistochemistry and LysoPLD activity measurement. ATX Tg mice exhibited significantly increased IOP for nearly two months following tamoxifen treatment, with no anterior segment changes or inflammation. Immunohistochemical analysis revealed enhanced expression of extracellular matrix near the angle after two weeks and three months of ATX induction. This correlated with reduced outflow facility, indicating that sustained ATX overexpression induces angle fibrosis, elevating IOP. Although inner retinal layer thickness remained stable, peripheral retina showed a notable reduction in RGC cell count. Conclusions: These findings confirm the successful creation of an open-angle OH mouse model, in which ATX expression in the eye prompts fibrosis near the angle and maintains elevated IOP over extended periods.
MeSH term(s)	Humans ; Animals ; Mice ; Glaucoma, Open-Angle ; Glaucoma ; Ocular Hypertension ; Disease Models, Animal ; Biomarkers ; Inflammation ; Fibrosis ; Tamoxifen
Chemical Substances	Biomarkers ; Tamoxifen (094ZI81Y45)
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.65.2.32
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Article ; Online: Effect of a fixed combination of ripasudil and brimonidine on aqueous humor dynamics in mice.

Yamagishi-Kimura, Reiko / Honjo, Megumi / Aihara, Makoto

Scientific reports

2024 Volume 14, Issue 1, Page(s) 7861

Abstract: Ripasudil-brimonidine fixed-dose combination (K-232) simultaneously targets three different intraocular pressure (IOP) lowering mechanisms, increasing trabecular meshwork outflow and uveoscleral outflow, and reducing aqueous humor production Vascularly, ... ...

Abstract	Ripasudil-brimonidine fixed-dose combination (K-232) simultaneously targets three different intraocular pressure (IOP) lowering mechanisms, increasing trabecular meshwork outflow and uveoscleral outflow, and reducing aqueous humor production Vascularly, ripasudil induces transient vasodilation, brimonidine transient vasoconstriction. Investigating effects on IOP, aqueous dynamics, and EVP in mice eyes by microneedle and constant-pressure perfusion methods, and on cytoskeletal and fibrotic proteins changes in HTM cells by a gel contraction assay and immunocytochemistry. Ripasudil, K-232, and brimonidine droplets significantly reduced IOP at 30 min, with K-232 sustaining the effect at 60 min. For EVP, only K-232 exhibited reduced EVP until 60 min after instillation. In vitro, ripasudil inhibited gel contractility and TGFβ2-induced fibrotic changes, whereas brimonidine did not. K-232 significantly lowered IOPs in mice by combining the effects of ripasudil and brimonidine. Brimonidine alone also showed IOP reductions with enhanced outflow facility, and the drug did not interfere with the effects of ripasudil on the trabecular meshwork outflow; K-232 and ripasudil alone both significantly lowered the EVP and enhanced outflow facility, demonstrating that K-232 efficiently reduces IOPs.
MeSH term(s)	Animals ; Mice ; Brimonidine Tartrate/pharmacology ; Aqueous Humor/metabolism ; Intraocular Pressure ; Trabecular Meshwork/metabolism ; Isoquinolines ; Sulfonamides
Chemical Substances	Brimonidine Tartrate (4S9CL2DY2H) ; K-115 ; Isoquinolines ; Sulfonamides
Language	English
Publishing date	2024-04-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-58212-6
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Article ; Online: Effects of Brimonidine, Omidenepag Isopropyl, and Ripasudil Ophthalmic Solutions to Protect against H

Liu, Mengxuan / Honjo, Megumi / Yamagishi, Reiko / Aihara, Makoto

Current eye research

2023 Volume 48, Issue 11, Page(s) 1014–1025

Abstract: Purpose: We investigated whether hydrogen peroxide (H: Methods: We used commercially available ophthalmic solutions of brimonidine, omidenepag isopropyl, and ripasudil in the study. HTM cells were exposed to H: Results: HTM cell viability ... ...

Abstract	Purpose: We investigated whether hydrogen peroxide (H Methods: We used commercially available ophthalmic solutions of brimonidine, omidenepag isopropyl, and ripasudil in the study. HTM cells were exposed to H Results: HTM cell viability decreased and SA-β-Gal activity increased significantly after exposure to H Conclusion: In vitro
Language	English
Publishing date	2023-07-19
Publishing country	England
Document type	Journal Article
ZDB-ID	82079-9
ISSN	1460-2202 ; 0271-3683
ISSN (online)	1460-2202
ISSN	0271-3683
DOI	10.1080/02713683.2023.2235892
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Article ; Online: The effect of axial length on the short-term outcomes of cataract surgery combined with ab interno trabeculotomy.

Goto, Hiroki / Honjo, Megumi / Omoto, Takashi / Aihara, Makoto

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie

2023 Volume 262, Issue 5, Page(s) 1599–1606

Abstract: Purpose: Minimally invasive glaucoma surgery is safer and effective surgical modality for patients with glaucoma. To compare the effect of axial length (AL) on the surgical outcomes of combined cataract surgery and ab interno trabeculotomy (phaco-LOT), ... ...

Abstract	Purpose: Minimally invasive glaucoma surgery is safer and effective surgical modality for patients with glaucoma. To compare the effect of axial length (AL) on the surgical outcomes of combined cataract surgery and ab interno trabeculotomy (phaco-LOT), a retrospective, non-randomized comparative study was performed. Methods: In total, 458 eyes of 458 open-angle glaucoma patients who underwent phaco-LOT and were followed-up without any intervention for at least 6 months were enrolled. All were divided into a long-AL group (AL ≥ 26.0 mm, 123 eyes) and a not-long-AL group (AL < 26.0 mm, 335 eyes). The principal outcomes were the changes in intraocular pressure (IOP) and medication scores. We also sought a correlation between postoperative IOP spike and hyphema. Results: Significant postoperative reductions in IOP and medication scores were apparent in all subjects. The IOP reductions were significant at all timepoints in the not-long-AL group, but not until 1 month postoperatively in the long-AL group, and the IOP change was significantly lower in the long-AL group from postoperative day 1 to 3 months. On subanalysis of subjects by age, the microhook used, the pre-operative IOP, and the medication score, a significantly higher incidence of IOP spike was observed in the long-AL group in weeks 1 and 2 (both p < 0.05), but this did not correlate with hyphema status, implying that a different mechanism was in play. Conclusion: Phaco-LOT was effective regardless of AL, but the postoperative IOP decrease was lower and the early postoperative incidence of IOP spike was higher in long-AL eyes.
MeSH term(s)	Humans ; Glaucoma, Open-Angle/complications ; Glaucoma, Open-Angle/surgery ; Hyphema/etiology ; Hyphema/surgery ; Retrospective Studies ; Trabeculectomy/adverse effects ; Glaucoma/surgery ; Intraocular Pressure ; Trabecular Meshwork/surgery ; Ocular Hypotension/surgery ; Cataract/complications ; Treatment Outcome
Language	English
Publishing date	2023-12-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	8435-9
ISSN	1435-702X ; 0721-832X
ISSN (online)	1435-702X
ISSN	0721-832X
DOI	10.1007/s00417-023-06337-1
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Article ; Online: Apoptosis inhibitor of macrophages/CD5L enhances phagocytosis in the trabecular meshwork cells and regulates ocular hypertension.

Nemoto, Hotaka / Honjo, Megumi / Arai, Satoko / Miyazaki, Toru / Aihara, Makoto

Journal of cellular physiology

2023 Volume 238, Issue 10, Page(s) 2451–2467

Abstract: The trabecular meshwork (TM) cells of the eye are important for controlling intraocular pressure (IOP) and regulating outflow resistance in the aqueous humor. TM cells can remove particles and cellular debris by phagocytosis, decreasing both outflow ... ...

Abstract	The trabecular meshwork (TM) cells of the eye are important for controlling intraocular pressure (IOP) and regulating outflow resistance in the aqueous humor. TM cells can remove particles and cellular debris by phagocytosis, decreasing both outflow resistance and IOP. However, the underlying mechanisms remain unclear. Here, we investigate whether apoptosis inhibitor of macrophages (AIM), which mediates the removal of dead cells and debris in renal tubular epithelial cells, regulates the phagocytic capacity of TM cells. In vitro experiments revealed that CD36, the main receptor for AIM, colocalized with AIM in human TM cells; additionally, phagocytosis was stimulated when AIM was provided. Furthermore, in a mouse model with transient IOP elevation induced by laser iridotomy (LI), removal of accumulated iris pigment epithelial cells or debris in the TM and recovery of IOP to baseline levels were delayed in AIM
Language	English
Publishing date	2023-08-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.31097
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Article ; Online: The Roles Played by FP/EP3 Receptors During Pressure-lowering in Mouse Eyes Mediated by a Dual FP/EP3 Receptor Agonist.

Yamagishi-Kimura, Reiko / Honjo, Megumi / Aihara, Makoto

Investigative ophthalmology & visual science

2022 Volume 63, Issue 2, Page(s) 24

Abstract: Purpose: We investigated the intraocular pressure (IOP)-lowering effect of topical sepetaprost (SPT), a dual agonist of the FP and EP3 receptors. We explored whether certain receptors mediated the hypotensive effect of SPT and outflow facility changes ... ...

Abstract	Purpose: We investigated the intraocular pressure (IOP)-lowering effect of topical sepetaprost (SPT), a dual agonist of the FP and EP3 receptors. We explored whether certain receptors mediated the hypotensive effect of SPT and outflow facility changes in C57BL/6 mice (wild-type [WT]) and FP and EP3 receptor-deficient mice (FPKO and EP3KO mice, respectively). Methods: IOP was measured using a microneedle. Outflow facility was measured using a two-level, constant-pressure perfusion method. Results: SPT significantly reduced IOP for 8 hours after administration to WT mice. The 2-hour IOP reductions afforded by latanoprost were 15.3 ± 2.5, 1.8 ± 2.0, and 12.3 ± 2.4% in WT, FPKO, and EP3KO mice, respectively; the SPT figures were 13.6 ± 2.1, 5.9 ± 2.7, and 6.6 ± 2.6%, respectively. Latanoprost-mediated IOP reduction was significantly decreased in FPKO mice, and SPT-mediated IOP reduction was reduced in both FPKO and EP3KO mice. At 6 hours after administration, latanoprost did not significantly reduce the IOP in any tested mouse strain. SPT-mediated IOP reduction was reduced in both FPKO and EP3KO mice. IOP reduction at 6 hours was significantly higher after simultaneous administration of selective FP and EP3 receptor agonists, but IOP did not fall on administration of (only) a selective EP3 receptor agonist. SPT significantly increased outflow facility in WT mice, but less so in FPKO and EP3KO mice. Conclusions: The IOP-lowering effect of SPT lasted longer than that of latanoprost. Our data imply that this may be attributable to augmented outflow facility mediated by the FP and EP3 receptors.
MeSH term(s)	Administration, Ophthalmic ; Animals ; Antihypertensive Agents/therapeutic use ; Aqueous Humor/physiology ; Dinoprostone/analogs & derivatives ; Dinoprostone/therapeutic use ; Intraocular Pressure/drug effects ; Intraocular Pressure/physiology ; Latanoprost/therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Ophthalmic Solutions ; Oxepins/therapeutic use ; Receptors, Prostaglandin/agonists ; Receptors, Prostaglandin/physiology ; Receptors, Prostaglandin E, EP3 Subtype/agonists ; Receptors, Prostaglandin E, EP3 Subtype/physiology ; Time Factors ; Tonometry, Ocular
Chemical Substances	Antihypertensive Agents ; ONO AE 248 ; Ophthalmic Solutions ; Oxepins ; Receptors, Prostaglandin ; Receptors, Prostaglandin E, EP3 Subtype ; prostaglandin F2alpha receptor ; Latanoprost (6Z5B6HVF6O) ; propan-2-yl 4-(6-(4-(2,5-difluorophenoxy)-3-hydroxybut-1-en-1-yl)-7-hydroxyoctahydro-2H-cyclopenta(b)oxepin-3-yl)butanoate (79O7855J4G) ; Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2022-02-25
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.63.2.24
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Article ; Online: Visual cortex damage in a ferret model of ocular hypertension.

Fujishiro, Takashi / Honjo, Megumi / Kawasaki, Hiroshi / Aihara, Makoto

Japanese journal of ophthalmology

2022 Volume 66, Issue 2, Page(s) 205–212

Abstract: Purpose: We aimed to analyze the changes in the visual cortex of a ferret model of ocular hypertension (OH) using cytochrome oxidase (CO) staining.: Study design: Experimental.: Methods: OH was induced in 9 ferrets by means of injection of ... ...

Abstract	Purpose: We aimed to analyze the changes in the visual cortex of a ferret model of ocular hypertension (OH) using cytochrome oxidase (CO) staining. Study design: Experimental. Methods: OH was induced in 9 ferrets by means of injection of cultured conjunctival cells into the anterior chamber of the right eye. Three ferrets were used as the controls. CO staining was performed to assess the metabolic intensity at the II-III and IVC layers of the visual cortex. Results: The intensities of CO staining in the right and left II-III layers of the primary visual cortex (V1) in the OH ferrets were 39.8 ± 10.3 and 41.9 ± 9.2 arbitrary units, respectively. In the control ferrets, the intensity was 88.1 ± 8.1 arbitrary units. The intensity of CO staining of the II-III layers obtained from the OH eyes was significantly lower than that from the control eyes (unpaired t test, P < .01). The intensities of CO staining in the right and left IVC layers of V1 in the OH ferrets were 60.3 ± 12.8 and 60.0 ± 13.5 arbitrary units, respectively. In the control ferrets, the intensity was 111.4 ± 9.6 arbitrary units. The CO staining intensity of the IVC layer obtained from the OH eyes was significantly lower than that from the control eyes (unpaired t test, P < .01). Conclusion: The CO staining intensity was reduced in the visual cortex from OH eyes. This study revealed that OH causes metabolic change in the visual cortex.
MeSH term(s)	Animals ; Electron Transport Complex IV/metabolism ; Ferrets/metabolism ; Glaucoma ; Ocular Hypertension/diagnosis ; Visual Cortex/metabolism
Chemical Substances	Electron Transport Complex IV (EC 1.9.3.1)
Language	English
Publishing date	2022-01-19
Publishing country	Japan
Document type	Journal Article
ZDB-ID	82032-5
ISSN	1613-2246 ; 0021-5155
ISSN (online)	1613-2246
ISSN	0021-5155
DOI	10.1007/s10384-022-00901-8
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Article ; Online: Contributing factors for intraocular pressure control in patients with mostly normal-tension glaucoma after initial Ex-PRESS drainage device implantation.

Aoyama, Yurika / Sakata, Rei / Fujishiro, Takashi / Honjo, Megumi / Shirato, Shiroaki / Aihara, Makoto

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie

2023 Volume 262, Issue 1, Page(s) 191–201

Abstract: Purpose: To investigate the postoperative intraocular pressure (IOP) control and identify the factors associated with failure of initial Ex-PRESS surgery in patients with open-angle glaucoma for 3 years.: Methods: A total of 79 patients with ... ...

Abstract	Purpose: To investigate the postoperative intraocular pressure (IOP) control and identify the factors associated with failure of initial Ex-PRESS surgery in patients with open-angle glaucoma for 3 years. Methods: A total of 79 patients with medically uncontrolled open-angle glaucoma (55 normal-tension glaucoma and 24 primary open-angle glaucoma) were enrolled. All patients underwent Ex-PRESS implantation (including combined cataract surgery). The outcome measure was the survival rate using life table analysis, the failure was defined as IOP of > 18 mmHg (criterion A), > 15 mmHg (criterion B) or > 12 mmHg (criterion C) and/or IOP reduction of < 20% from baseline (each criterion) without any glaucoma medications. The Cox proportional hazards model was used to identify risk factors for IOP management defined as the above criterion. RESULTS: The mean preoperative IOP was 19.3 ± 5.8 mmHg. At 36 months, the mean IOP was 11.8 ± 3.6 mmHg with a mean IOP change of 7.5 mmHg (reduction rate 39.0%). The cumulative probability of success was 58% (95%CI: 42-64%) (criterion A), 48% (95%CI: 37-59%) (criterion B) and 30% (95%CI: 20-40%) (criterion C). In multivariate analyses, factors that predicted poor IOP control included the intervention of bleb needling after 6 months after the surgery (HR: 2.43; 95%CI: 1.35-4.37; P = 0.032). Transient hypotony was observed in 4 patients. Conclusion: The implementation of bleb needling after Ex-PRESS surgery in the late postoperative period was suggested to be the main risk factor for achieving lower IOP.
MeSH term(s)	Humans ; Intraocular Pressure ; Glaucoma, Open-Angle/surgery ; Glaucoma, Open-Angle/complications ; Glaucoma Drainage Implants ; Follow-Up Studies ; Glaucoma/surgery ; Low Tension Glaucoma/diagnosis ; Low Tension Glaucoma/surgery ; Low Tension Glaucoma/complications ; Drainage ; Treatment Outcome ; Trabeculectomy
Language	English
Publishing date	2023-08-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	8435-9
ISSN	1435-702X ; 0721-832X
ISSN (online)	1435-702X
ISSN	0721-832X
DOI	10.1007/s00417-023-06209-8
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Article ; Online: Synergic effects of EP2 and FP receptors co-activation on Blood-Retinal Barrier and Microglia.

Nakamura, Natsuko / Honjo, Megumi / Yamagishi, Reiko / Sakata, Rei / Watanabe, Sumiko / Aihara, Makoto

Experimental eye research

2023 Volume 237, Page(s) 109691

Abstract: Macular edema (ME) is caused with disruption of the blood-retinal barrier (BRB) followed by fluid accumulation in the subretinal space. Main components of the outer and inner BRB are retinal pigment epithelial (RPE) cells and retinal microvascular ... ...

Abstract	Macular edema (ME) is caused with disruption of the blood-retinal barrier (BRB) followed by fluid accumulation in the subretinal space. Main components of the outer and inner BRB are retinal pigment epithelial (RPE) cells and retinal microvascular endothelial cells, respectively. In addition, glial cells also participate in the functional regulation of the BRB as the member of 'neurovascular unit'. Under various stresses, cells in neurovascular units secrete inflammatory cytokines. Neuroinflammation induced by these cytokines can cause BRB dysfunction by degrading barrier-related proteins and contribute to the pathophysiology of ME. Prostaglandins (PGs) are crucial lipid mediators involved in neuroinflammation. Among PGs, a novel EP2 agonist, omidenepag (OMD) acts on not only the uveoscleral pathway but also the conventional pathway, unlike F prostanoid (FP) receptor agonists. Moreover, the combination use of the EP and the FP agonist is not recommended because of the risk of inflammation. In this study, we investigated effects of OMD and latanoprost acid (LTA), a FP agonist, on BRB and microglia in vitro and in vivo. To investigate the function of outer/inner BRB and microglia, in vitro, ARPE-19 cells, human retinal microvascular endothelial cells (HRMECs), and MG5 cells were used. Cell viability, inflammatory cytokines mRNA and protein levels, barrier morphology/function, and microglial activation were evaluated using proliferation assays, qRT-PCR, ELISA, immunocytochemistry, trans-epithelial electrical resistance, and permeability assay. Moreover, after vitreous injection into the mouse, outer BRB morphology, glial activation, and cytokine expression were assessed. Each OMD and LTA alone did not affect the viability or cytokines expression of the three types of cells. In ARPE-19 cells, the co-stimulation of OMD and LTA increased the mRNA and protein levels of inflammatory cytokines (IL-6, TNF-α, and VEGF-A) and decreased the barrier function and the junction-related protein (ZO-1 and β-catenin). By contrast in HRMECs, the co-stimulation affected significant differences in the mRNA levels of some cytokine (IL-6 and TNF-α) but enhanced the barrier function. In MG5 cells, the cytokines mRNA and size of Iba1-expressed cell were increased. A non-steroidal anti-inflammatory inhibited the barrier dysfunction and the junction-related protein downregulation in ARPE-19 cells and activation of MG5 cells. Also in vivo, the co-stimulation induced outer BRB disruption, cytokine increase, and retinal glial activation. Therefore, the co-stimulation of EP2 and FP induced the inflammatory cytokine-mediated outer BRB disruption, the enhanced inner BRB function, and the microglial activation. The BRB imbalance and the intrinsic prostaglandin production may be involved in OMD-related inflammation.
MeSH term(s)	Mice ; Humans ; Animals ; Blood-Retinal Barrier ; Microglia/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Interleukin-6/metabolism ; Endothelial Cells/metabolism ; Neuroinflammatory Diseases ; Macular Edema/metabolism ; Cytokines/metabolism ; Inflammation/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	Tumor Necrosis Factor-alpha ; Interleukin-6 ; Cytokines ; RNA, Messenger
Language	English
Publishing date	2023-10-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2023.109691
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In stock of ZB MED Cologne/Königswinter

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Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito