• 한국임상약학회지
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• 제31권3호
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• pp.205-215
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• 2021

Background: The treatment of primary open-angle glaucoma (POAG) or ocular hypertension (OHT) for intraocular pressure (IOP) reduction is recommended to proceed with the use of the compound. Therefore, this study aimed to evaluate the efficacy and safety of brinzolamide combination therapy on POAG and OHT following the subgroup analysis among types of brinzolamide combined medications. Methods: By June 2019, PubMed, EMBASE and Cochrane Library were searched to find a study that met our inclusion criteria. Based on randomized control trials (RCTs), we collected studies that tested the brinzolamide combination therapy in POAG and OHT patients, and analyzed the literature identified by the results of the study on IOP reduction and adverse reactions. Results: A total of 13 literature was collected to conduct an analysis including 2,197 patients. The intervention included brinzolamide combination therapies, combined with timolol, brimonidine, PGA or combined with both brimonidine and PGA. The analysis showed significant decreasing tendency for values at morning and end treatment per day in the use of brinzolamide combination therapy in the absolute IOP change (mean difference (MD) -1.41; 95% CI -1.92, -0.90; p<0.001 vs. MD -1.46; 95% CI -2.03, -0.89; p<0.00001, respectively). We could see higher adverse reactions in the brinzolamide combination group using intervention (odds ratio 1.43; 95% CI 1.20, 1.71; p<0.0001). Conclusion: Regarding IOP reduction in POAG and OHT patients, brinzolamide combination therapy is more effective but less safe than control treatment, which diverse among types of combined medications. Thus, more individualized therapy should be applied in real-world practice.

• Yonsei Medical Journal
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• 제59권9호
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• pp.1115-1122
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• 2018

Purpose: To investigate biomechanical properties of the cornea using a dynamic Scheimpflug analyzer according to age. Materials and Methods: In this prospective, cross-sectional, observational study, participants underwent ophthalmic investigations including corneal biomechanical properties, keratometric values, intraocular pressure (IOP), and manifest refraction spherical equivalent (MRSE). We determined the relationship of biomechanical parameters and ocular/systemic variables (participant's age, MRSE, IOP, and mean keratometric values) by piecewise regression analysis, association of biomechanical parameters with variables by Spearman's correlation and stepwise multiple regression analyses, and reference intervals (RI) by the bootstrap method. Results: This study included 217 eyes of 118 participants (20-81 years of age). Piecewise regression analysis between Corvis-central corneal thickness (CCT) and participant's age revealed that the optimal cut-off value of age was 45 years. No clear breakpoints were detected between the corneal biomechanical parameters and MRSE, IOP, and mean keratometric values. Corneal velocity, deformation amplitude, radius, maximal concave power, Corvis-CCT, and Corvis-IOP exhibited correlations with IOP, regardless of age (all ages, 20-44 years, and over 44 years). With smaller deformation amplitude and corneal velocity as well as increased CorvisIOP and Corvis-CCT, IOP became significantly increased. We provided the results of determination of confidence interval from RI data using bootstrap method in three separate age groups (all ages, 20-44 years, and over 44 years). Conclusion: We demonstrated multiple corneal biomechanical parameters according to age, and reported that the corneal biomechanical parameters are influenced by IOP.

• 고신대학교 의과대학 학술지
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• 제33권3호
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• pp.318-327
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• 2018

Objectives: To investigate the effect of absorbable suture on surgically-induced corneal astigmatism in 3.0-mm sclera tunnel cataract surgeries. Methods: Medical records of patients who underwent phacoemulsification cataract surgery using a 3.0-mm sclera tunnel incision made by a single surgeon were reviewed. Uncorrected distant visual acuity, corneal astigmatism and surgically-induced astigmatism were measured in 56 patients' eyes that underwent sclera tunnel cataract surgery with absorbable sutures (sutured group) and in 23 patients' eyes without sutures (unsutured group). Uncorrected visual acuity, intraocular pressure, slit lamp examination, and automated keratometry were evaluated preoperatively and at 3 days, 2 weeks, 4 weeks, and 8 weeks after cataract operation. Results: There were no significant differences in preoperative average uncorrected distant visual acuity of the two groups (sutured group: $0.79{\pm}0.64$, unsutured group: $0.68{\pm}0.72$, P = 0.145). Corneal astigmatism measured using keratometry in the sutured and unsutured group at postoperative day 3 were $2.27{\pm}2.12D$ versus $0.83{\pm}0.55D$ at (P < 0.001), a difference which had disappeared after 4 weeks. Surgically induced astigmatism using the Holladay and Vector methods showed similar outcomes, suggesting that the sutured group exhibited higher astigmatism compared with the unsutured group until 2 weeks post-surgery. Conclusions: TPatients undergoing scleral tunnel cataract surgery with absorbable sutures have greater surgically induced astigmatism, especially in the early postoperative period, compared with those without sutures. However, this surgically induced astigmatism due to absorbable sutures in scleral tunnel cataract surgery is temporary and disappears at 4 weeks post-surgery.

• 운동과학
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• 제26권3호
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• pp.229-237
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• 2017

PURPOSE: This study was to investigate the Glycolysis mediated sarcoplasmic reticulum (SR) $Ca^{2+}$ signal regulates mitochondria $Ca^{2+}$ during skeletal muscle contraction by using glycolysis inhibitor. METHODS: To examine the effect of Glycolysis inhibitor on SR and mitochondria $Ca^{2+}$ content, we used skeletal muscle fiber from gastrocnemius muscle. 2-deoxy glucose and 3-bromo pyruvate used as glycolysis inhibitor, it applied to electrically stimulated muscle contraction experiment. Intracellular $Ca^{2+}$ content, SR, mitochondria $Ca^{2+}$ level and mitochondria membrane potential (MMP) was detected by confocal microscope. Mitochondrial energy metabolism related enzyme, citric acid synthase activity also examined for mitochondrial function during the muscle contraction. RESULTS: Treatment of 2-DG and 3BP decreased the muscle contraction induced SR $Ca^{2+}$ increase however the mitochondria $Ca^{2+}$ level was increased by treatment of inhibitors and showed and overloading as compared with the control group. Glycolysis inhibitor and thapsigargin treatment showed a significant decrease in MPP of skeletal muscle cells compared to the control group. CS activity significantly decreased after pretreatment of glycolysis inhibitor during skeletal muscle contraction. These results suggest that regulation of mitochondrial $Ca^{2+}$ levels by glycolysis is an important factor in mitochondrial energy production during skeletal muscle contraction CONCLUSIONS: These results suggest that mitochondria $Ca^{2+}$ level can be regulated by SR $Ca^{2+}$ level and glycolytic regulation of intraocular $Ca^{2+}$ signal play pivotal role in regulation of mitochondria energy metabolism during the muscle contraction.

• 대한수의학회지
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• 제62권3호
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• pp.26.1-26.7
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• 2022

This study was aimed to evaluate the prophylactic anti-glaucoma effect of topical 5% betaxolol (BTX) and 2% dorzolamide (DRZ) on the second eye in dogs with unilateral primary angle closure glaucoma (PACG). Medical records of 60 dogs with unilateral PACG who received prophylactic anti-glaucoma eyedrops in the second eye, from 2016 to 2021, were reviewed. The prophylactic effects of BTX were maintained on 28/60 (46.7%) eyes until last visit and BTX failure was observed on median 510 (range, 53-1,927) days in 32/60 (53.3%) eyes. After DRZ instillation in BTX failure eyes, the prophylactic effects were extended at median 610 (range, 157-2,270) days in 21/32 (65.6%) eyes. DRZ failure eyes (17/21, 81.0%) eyes required chemical ablation or surgical intervention due to uncontrolled intraocular pressure. The duration of prophylactic effects was decreased with aging (R² = 0.334, p = 0.006). The predominant breeds were Shih-Tzu (41.9%) and American Cocker Spaniel (30.6%) with no significant differences in survival curves (p = 0.210). The average prophylactic effects of BTX persisted more than 1.5 year and could be selected the first prophylactic eye drop in unilateral PACG. Also, early surgical intervention should be considered in prophylactic medications failure cases.

• 한국동물위생학회지
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• 제45권3호
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• pp.221-228
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• 2022

Cataracts occur commonly in older dogs, which can lead to partial or complete vision loss. In the present study, a 12-year-old male poodle presented for evaluation of ocular sinister (OS) cataract. This study was a clinical case report on the process of performing surgery using phacoemulsification (PHACO) and the problems that arise in patient diagnosed with OS cataract. In the oculus dexter (OD), the artificial eye was inserted because there was no electroretinography (ERG) response. In the OS, the ERG was 51.6 μV, so operation was performed because the visual pathway function remained. Slit-lamp biomicroscopy of the OS showed complete loss of vision as a hypermature cataract and that the lens was hardened. During the cataract surgery using PHACO, visco-elastic agents were used to maintain the shape of the eyeball, and the PHACO procedure took 3.13 minutes. The hardened lens and visco-elastic agents were removed from the eye through PHACO surgery, and the operation was completed by inserting an intraocular lens (IOL). As a result of managing IOP for 2 months after surgery, it remained stable at a maximum of 19 mmHg, and no postoperative ocular hypertension (POH) occurred. Currently, one year has passed since the operation, and the dog maintains its daily life with its left eye without any problems.

• Molecules and Cells
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• 제46권7호
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• pp.420-429
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• 2023

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.

• Journal of Veterinary Science
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• 제24권4호
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• pp.59.1-59.13
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• 2023

Background: Rocuronium bromide has been evaluated as a mydriatic agent in birds, but the species applied were limited and the dose and effect were variable. Objective: This study aims to evaluate the efficacy of topical rocuronium bromide as mydriatics in 4 species according to horizontal palpebral fissure length: Feral pigeon (Columba livia), Common kestrel (Falco tinnunculus), Northern boobook (Ninox japonica), and Eurasian eagle owl (Bubo bubo). Methods: A total of 32 birds (8 for each species) were included as pre-releasing examination. Rocuronium bromide was instilled in one randomly selected eye of each bird based on palpebral fissure length criteria (0.5 mg/50 µL for pigeons, 1 mg/100 µL for kestrels and boobook owls, and 2 mg/200 µL for eagle owls). The contralateral eye was used as control and treated with normal saline. After instillation of the drug, pupil diameter, pupillary light reflex, intraocular pressure, heart rate, and respiratory rate were evaluated at 10 min intervals up to 180 min and at 30 min intervals up to 360 min. Results: Statistically significant mydriasis was obtained in all birds (p < 0.001). However, in boobook and eagle owls, marked mydriasis persisted until 360 min. Side effects including corneal erosion and lower eyelid paralysis were common, which was observed in 26/32 birds. Blepharospasm was also noted during this study. No systemic adverse signs were observed. Conclusions: Rocuronium bromide could be a good mydriatics option for 4 species of birds, however, further studies are needed to find lowest effective dose to reduce drug-related side effects.

• Journal of Veterinary Science
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• 제24권4호
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• pp.34.1-34.12
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• 2023

Background: There has not been a thoroughly reported study of the comparison between spectral domain-optical coherence tomography (SD-OCT) with both ultrasound biomicroscopy (UBM) and gonioscopy on the evaluation of the iridocorneal angle (ICA) in dogs. Objectives: To investigate the diagnostic value of SD-OCT for the early detection of narrowing ICA by comparing and assessing inter-device agreement in anterior chamber angle (ACA) measurements obtained by SD-OCT and UBM, and ICA evaluations by gonioscopy. Methods: A total of 28 eyes from 28 client-owned dogs with normal intraocular pressure were included for examination. The ACA and angle opening distance (AOD) were measured from the SD-OCT and UBM images, and gonioscopy images were analyzed using the ICA grade and ZibWest angle index. Results: The mean ACA and AOD for SD-OCT were 28.31° ± 5.37° and 658.42 ± 219.90 ㎛, and for UBM, 28.34° ± 5.82° and 859.29 ± 221.80 ㎛, respectively. The mean difference in ACA between the average values of SD-OCT and UBM measurements was 0.03° with a 95% limit of agreement (LoA) span of 16.2°, indicating positive agreement; that in AOD was 200.85 ㎛ with a 95% LoA span of 1,110.95 ㎛, indicating poor agreement. The Pearson correlation coefficient of the ACA of SD-OCT and ZibWest indices of gonioscopy was 0.624, indicating strong agreement; that of UBM and gonioscopy was 0.43, indicating moderate agreement. Conclusions: SD-OCT is well tolerated by canine patients due to its non-contact method and might be an alternative option for early screening of ICA narrowing in clinical settings.

• The Korean Journal of Physiology and Pharmacology
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• 제28권4호
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• pp.345-359
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• 2024

Deposition of extracellular matrix (ECM) in the trabecular meshwork (TM) increases aqueous humour outflow resistance leading to elevation of intraocular pressure (IOP) in primary open-angle glaucoma, which remains the only modifiable risk factor. Resveratrol has been shown to counteract the steroid-induced increase in IOP and increase the TM expression of ECM proteolytic enzymes; however, its effects on the deposition of ECM components by TM and its associated pathways, such as TGF-β-SMAD signalling remain uncertain. This study, therefore, explored the effects of trans-resveratrol on the expression of ECM components, SMAD signalling molecules, plasminogen activator inhibitor-1 and tissue plasminogen activator in dexamethasone-treated human TM cells (HTMCs). We also studied the nature of molecular interaction of trans-resveratrol with SMAD4 domains using ensemble docking. Treatment of HTMCs with 12.5 µM trans-resveratrol downregulated the dexamethasone-induced increase in collagen, fibronectin and α-smooth muscle actin at gene and protein levels through downregulation of TGF-β1, SMAD4, and upregulation of SMAD7. Downregulation of TGF-β1 signalling by trans-resveratrol could be attributed to its effect on the transcriptional activity due to high affinity for the MH2 domain of SMAD4. These effects may contribute to resveratrol's IOP-lowering properties by reducing ECM deposition and enhancing aqueous humour outflow in the TM.