Language：English   Publishing type：Research paper (scientific journal)  

FROUNT is an intracellular protein that promotes pseudopodia formation by binding to the chemokine receptors CCR2 and CCR5 on macrophages. Recently, disulfiram (DSF), a drug treatment for alcoholism, was found to have FROUNT inhibitory activity. In this study, we investigated the effect of DSF eye drops in a rat corneal alkali burn model. After alkali burn, 0.5% DSF eye drops (DSF group) and vehicle eye drops (Vehicle group) were administered twice daily. Immunohistochemical observations and real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed at 6 h and 1, 4, and 7 days after alkali burn. Results showed a significant decrease in macrophage accumulation in the cornea in the DSF group, but no difference in neutrophils. RT-PCR showed decreased expression of macrophage-associated cytokines in the DSF group. Corneal scarring and neovascularization were also suppressed in the DSF group. Low-vacuum scanning electron microscopy imaging showed that macrophage length was significantly shorter in the DSF group, reflecting the reduced extension of pseudopodia. These results suggest that DSF inhibited macrophage infiltration by suppressing macrophage pseudopodia formation.

DOI： 10.3390/ijms24010735

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：日本緑内障学会  

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Language：Japanese   Publisher：日本緑内障学会  

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Language：Japanese   Publisher：日本緑内障学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Many studies have demonstrated the therapeutic effects of hydrogen in pathological conditions such as inflammation; however, little is known about its prophylactic effects. The purpose of this study is to investigate the prophylactic effects of hydrogen-rich water instillation in a rat corneal alkali burn model. Hydrogen-rich water (hydrogen group) or physiological saline (vehicle group) was instilled continuously to the normal rat cornea for 5 min. At 6 h after instillation, the cornea was exposed to alkali. The area of corneal epithelial defect (CED) was measured every 6 h until 24 h after alkali exposure. In addition, at 6 and 24 h after injury, histological and immunohistochemical observations were made and real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to investigate superoxide dismutase enzyme (SOD)1, SOD2, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) mRNA expression. CED at 12 h and the number of inflammatory infiltrating cells at 6 h after injury were significantly smaller in the hydrogen group than the vehicle group. Furthermore, SOD1 expression was significantly higher in the hydrogen group than the vehicle group at both 6 and 24 h, and the number of PGC-1α-positive cells was significantly larger in the hydrogen group than the vehicle group at 6 h after injury. In this model, prophylactic instillation of hydrogen-rich water suppressed alkali burn-induced inflammation, likely by upregulating expression of antioxidants such as SOD1 and PGC-1α. Hydrogen has not only therapeutic potential but also prophylactic effects that may suppress corneal scarring following injury and promote wound healing.

DOI： 10.3390/ijms23179774

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Language：Japanese   Publisher：(株)メディカル葵出版  

目的:広義原発開放隅角緑内障(POAG)におけるカルテオロール/ラタノプロスト配合点眼剤(以下、CAR/LAT)単独への変更による1年間の眼圧下降効果を後ろ向きに検討する。対象および方法:プロスタグランジン関連薬(以下、PG)単剤または異種のPG/β遮断薬配合剤(以下、PG/β)単独からの切り替えで、CAR/LATを新規に処方した広義POAG患者のうち、緑内障手術歴のない連続65例を対象とした。変更前と変更1ヵ月後、3ヵ月後、6ヵ月後、12ヵ月後の眼圧をそれぞれ比較した。結果:PGからの変更では、眼圧(平均±標準偏差)は、変更前14.9±3.2mmHgに対して変更12ヵ月後12.8±2.1mmHgで、変更前と比べて変更後のすべての時点で有意な眼圧下降を認めた(p<0.05)。異種のPG/βからの変更では、有意な変化はなかった(p=0.30)。結論:広義POAGにおいて、PG単剤からCAR/LATへの変更では、1年間有意な眼圧下降が得られ、また、異種のPG/β単独からの変更では有意な眼圧変化はない。(著者抄録)

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(公財)日本眼科学会  

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Language：Japanese   Publisher：(公社)日本眼科手術学会  

背景:外傷性眼球破裂は眼科緊急疾患のなかでもっとも予後の悪い疾患の一つであり、速やかな治療介入を要する。眼球破裂では、創傷を受けやすい眼球部位があることは知られているが、縫合治療後の創傷部の強度に関してはよくわかっていない。今回、同側に二度の外傷性眼球破裂を発症したが、二度目の創傷部が初回とは異なる部位であった症例を経験したため報告する。症例:94歳、女性。2020年8月25日、転倒による右眼球破裂にて日本医科大学附属病院眼科を紹介受診。2018年にも転倒時に右眼球破裂を起こし、他院にて強膜縫合術を受けた既往があった。同日、角膜・強膜縫合術を施行した。所見:鼻側角膜輪部強膜に裂傷、一部ぶどう膜脱出を認めたが、前回破裂部位の耳側角膜強膜には10-0ナイロン糸で縫合が密に施されており、同部位の眼球形態は保たれていた。今回の破裂部位に対して角膜・強膜縫合術を施行し、術後経過は良好であった。結論:外傷性眼球破裂の既往がある眼球に、再度外傷による破裂を起こした症例を経験した。前回、破裂を生じた強膜部位は二度目の破裂時には保たれており、縫合により強度が高められていると思われた。創傷部を適切に縫合することで外傷強度が向上することが示唆された。(著者抄録)

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Language：Japanese   Publisher：日本緑内障学会  

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Language：Japanese   Publisher：日本緑内障学会  

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Publishing type：Research paper (scientific journal)   Publisher：Medical Association of Nippon Medical School  

DOI： 10.1272/jnms.jnms.2021_88-305

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Decreased vision and cystoid macular edema (CME) developed in phakic eyes of a patient who underwent laser iridotomy after changing the glaucoma eye drops from carteolol 2% long-acting ophthalmic solution to omidenepag isopropyl 0.002%. CME completely disappeared at approximately 2 months after discontinuation of omidenepag isopropyl in conjunction with the use of bromfenac sodium 0.1%.

DOI： 10.1272/jnms.JNMS.2021_88-520

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Language：English   Publishing type：Research paper (scientific journal)  

The effects of each subtype-selective peroxisome proliferator activated receptor (PPAR) agonist (α, β/δ, γ) on corneal epithelial wound healing were investigated using a rat corneal alkali burn model. After the alkali burn, each PPAR agonist or vehicle ophthalmic solution was instilled topically onto the rat's cornea. Corneal epithelial healing processes were evaluated by fluorescein staining. Pathological analyses and real-time reverse transcription polymerase chain reactions were performed to evaluate Ki67 (proliferative maker) expression and inflammatory findings. The area of the corneal epithelial defect at 12 h and 24 h after the alkali burn was significantly smaller in each PPAR group than in the vehicle group. Ki67 mRNA expression was increased in the PPARβ/δ group, whereas mRNA expressions of inflammatory cytokines were suppressed in all of the PPAR agonist groups. Nuclear factor kappa B (NF-κB) was the most suppressed in the PPARγ group. The accelerated corneal epithelial healing effects of each PPAR ligand were thought to be related to the promotion of proliferative capacity and inhibition of inflammation.

DOI： 10.3390/ph14020088

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: The aim of this study was to measure serum levels of brain-derived neurotrophic factor (BDNF) in Japanese patients with primary open angle glaucoma (POAG) and normal tension glaucoma (NTG). METHODS: This was a prospective observational study of serum BDNF levels in 78 patients who underwent cataract surgery or trabeculectomy (27 glaucoma patients and 51 non-glaucoma cataract patients as controls). Patient age was 68.8 ± 11.1 years (mean ± standard deviation; range 35-86 years). The numbers of patients with POAG and NTG were 16 and 11, respectively. POAG was diagnosed by intraocular pressure measurement, gonioscopy, optic nerve head change, and presence of a visual field defect. RESULTS: Serum BDNF concentration was significantly lower in the glaucoma group (including both POAG and NTG) than in the control group (7.2 ± 3.6 ng/mL vs. 12.2 ± 9.3 ng/mL, p=0.004). Serum BDNF concentration was lower in early glaucoma than in moderate glaucoma. There was no correlation between serum BDNF concentration and age. When patients with NTG and POAG were compared, serum BDNF concentration was lower in the former. Serum BDNF concentration was not significantly correlated with glaucoma parameters, including optical coherence tomography and visual field defects. CONCLUSION: This is the first study to investigate serum BDNF concentration in glaucoma patients in Japan. Future studies should evaluate the role of BDNF as a potential biomarker of glaucoma.

DOI： 10.1272/jnms.JNMS.2020_87-605

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Language：English   Publishing type：Research paper (scientific journal)  

We describe the case of a primary open-angle glaucoma patient with re-elevated nocturnal sitting intraocular pressure (IOP) after restarting medical therapy due to a failing bleb. IOP was markedly higher than diurnal IOP during multiple-drug therapy in both eyes, but it did not increase in the left eye with a functional bleb without medical therapy after trabeculectomy with adjuvant mitomycin. However, nocturnal sitting IOP was re-elevated after restarting multiple-drug therapy due to a failing bleb, while diurnal IOP was maintained at a low level.

DOI： 10.1272/jnms.JNMS.2021_88-521

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Epiretinal membrane (ERM) is a disease that affects the vitreoretinal interface and causes metamorphopsia, anorthopia, and decreased visual acuity. In this study, ERM patients who underwent internal limiting membrane (ILM) peeling were classified as those with glaucoma (Group G) and a control group (Group C). Changes in ganglion cell complex (GCC) thickness were compared between these groups to investigate whether such changes had an effect on progression of glaucoma from structural change. METHODS: This was a retrospective, observational study that included 27 eyes of 27 patients. Group C included 22 eyes, and Group G included 5 eyes. Patients underwent ILM peeling, and cataract surgery was combined with vitrectomy for 16 phakic eyes; 2 phakic eyes and 9 aphakic eyes were treated only with vitrectomy. GCC thickness was measured preoperatively and at 2 weeks and 1, 3, and 6 months postoperatively, and these values and the rates of thinning were compared between the two groups. RESULTS: The mean age of patients was 66.7±12.8 years (range 30-84 years). There was no significant difference between groups in the thickness of the GCC or its rate of thinning after ILM peeling. CONCLUSIONS: The present results suggest that this procedure does not cause structural exacerbation of glaucoma in glaucoma patients. Although further studies of the functional effects of ILM peeling are required, the present results suggest that there is no significant difference between the two groups.

DOI： 10.1272/jnms.JNMS.2021_88-202

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Language：English   Publishing type：Research paper (scientific journal)  

The effects of peroxisome proliferator-activated receptor (PPAR)β/δ ophthalmic solution were investigated in a rat corneal alkali burn model. After alkali injury, GW501516 (PPARβ/δ agonist) or vehicle ophthalmic solution was topically instilled onto the rat's cornea twice a day until day 7. Pathological findings were evaluated, and real-time reverse transcription polymerase chain reaction was performed. GW501516 strongly suppressed infiltration of neutrophils and pan-macrophages, and reduced the mRNA expression of interleukin-6, interleukin-1β, tumor necrosis factor alpha, and nuclear factor-kappa B. On the other hand, GW501516 promoted infiltration of M2 macrophages, infiltration of vascular endothelial cells associated with neovascularization in the wounded area, and expression of vascular endothelial growth factor A mRNA. However, 7-day administration of GW501516 did not promote neovascularization in uninjured normal corneas. Thus, the PPARβ/δ ligand suppressed inflammation and promoted neovascularization in the corneal wound healing process. These results will help to elucidate the role of PPARβ/δ in the field of ophthalmology.

DOI： 10.3390/ijms21155296

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Language：English   Publishing type：Research paper (scientific journal)  

Peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ) agonists have anti-inflammatory and anti-neovascularization effects, but few reports have tested the combination of PPARα and PPARγ agonists. In this study, we investigated the therapeutic effects of ophthalmic solutions of agonists of PPARα, PPARγ, and the combination in a rat corneal alkali burn model. After alkali injury, an ophthalmic solution of 0.05% fenofibrate (PPARα group), 0.1% pioglitazone (PPARγ group), 0.05% fenofibrate + 0.1% pioglitazone (PPARα+γ group), or vehicle (vehicle group) was topically instilled onto the rat's cornea twice a day. After instillation, upregulation was seen of PPAR mRNA corresponding to each agonist group. Administration of agonists for PPARα, PPARγ, and PPARα+γ suppressed inflammatory cells, neovascularization, and fibrotic changes. In addition, the PPARγ agonist upregulated M2 macrophages, which contributed to wound healing, whereas the PPARα agonist suppressed immature blood vessels in the early phase. Administration of PPARα+γ agonists showed therapeutic effects in corneal wound healing, combining the characteristics of both PPARα and PPARγ agonists. The results indicate that the combination of PPARα and γ agonists may be a new therapeutic strategy.

DOI： 10.3390/ijms21145093

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Language：Japanese   Publisher：眼科臨床紀要会  

緒言:癌関連網膜症cancer-related retinopathy(CAR)は急激に進行する視力低下と視野狭窄を特徴とする。今回CARが疑われ、癌の早期治療により進行抑制できた1例を報告する。症例:58歳男性。急な両眼夜盲を自覚したため前医受診し、視野障害を認めたため紹介となった。矯正視力は両眼1.2だが、視野検査で輪状暗点を認め、網膜電図は平坦化し、光干渉断層撮影では中心窩周囲のellipsoid zoneの消失を認めた。同時期に肺小細胞癌が見つかり、初診時の7日後より化学放射線療法が開始された。CARを疑い抗リカバリン抗体を測定したが陰性だった。初診時より6ヵ月で視力、視野の増悪はなかった。考按:網膜色素変性様の症状と肺小細胞癌の罹患からCARを疑ったが、抗網膜抗体は特定できなかった。本例では肺癌の発見が眼症状出現とほぼ同時期であり、早期に化学放射線療法が開始されたため、視機能障害は軽度で保たれたのではないかと考えられた。(著者抄録)

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Language：Japanese   Publisher：眼科臨床紀要会  

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