• The Korean Journal of Physiology and Pharmacology
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• v.28 no.4
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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.

• Imaging Science in Dentistry
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• v.41 no.2
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• pp.71-78
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• 2011

Purpose : This study was performed to determine the optimal tile size for the fractal dimension of the mandibular trabecular bone using a tile counting method. Materials and Methods : Digital intraoral radiographic images were obtained at the mandibular angle, molar, premolar, and incisor regions of 29 human dry mandibles. After preprocessing, the parameters representing morphometric characteristics of the trabecular bone were calculated. The fractal dimensions of the processed images were analyzed in various tile sizes by the tile counting method. Results : The optimal range of tile size was 0.132 mm to 0.396 mm for the fractal dimension using the tile counting method. The sizes were closely related to the morphometric parameters. Conclusion : The fractal dimension of mandibular trabecular bone, as calculated with the tile counting method, can be best characterized with a range of tile sizes from 0.132 to 0.396 mm.

• Korean Journal of Veterinary Research
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• v.59 no.2
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• pp.109-111
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• 2019

A 10-year-old intact female Jindo dog was presented with a 1-week history of conjunctival redness and ocular discharge in the left eye. There was an absence of menace response, dazzle reflex, and direct pupillary light reflex. Slit-lamp biomicroscopy revealed corneal edema, ciliary flush, and aqueous flare. Intraocular pressure was 68 mmHg. Based on the information available, a diagnosis of glaucoma and uveitis was made. Subsequent histopathologic examination showed the glaucoma was produced by the effects of goniodysgenesis, posterior synechia, and pigment dispersion in the trabecular meshwork. This is the first report of primary glaucoma caused by goniodysgenesis in Jindo dogs.

• Genomics & Informatics
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• v.21 no.1
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• pp.6.1-6.8
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• 2023

Glaucoma is the second leading cause of irreversible blindness, and primary open-angle glaucoma (POAG) is the most common type. Due to inadequate diagnosis, treatment is often not administered until symptoms occur. Hence, approaches enabling earlier prediction or diagnosis of POAG are necessary. We aimed to identify novel drugs for glaucoma through bioinformatics and network analysis. Data from 36 samples, obtained from the trabecular meshwork of healthy individuals and patients with POAG, were acquired from a dataset. Next, differentially expressed genes (DEGs) were identified to construct a protein-protein interaction (PPI) network. In both stages, the genes were enriched by studying the critical biological processes and pathways related to POAG. Finally, a drug-gene network was constructed, and novel drugs for POAG treatment were proposed. Genes with p < 0.01 and |log fold change| > 0.3 (1,350 genes) were considered DEGs and utilized to construct a PPI network. Enrichment analysis yielded several key pathways that were upregulated or downregulated. For example, extracellular matrix organization, the immune system, neutrophil degranulation, and cytokine signaling were upregulated among immune pathways, while signal transduction, the immune system, extracellular matrix organization, and receptor tyrosine kinase signaling were downregulated. Finally, novel drugs including metformin hydrochloride, ixazomib citrate, and cisplatin warrant further analysis of their potential roles in POAG treatment. The candidate drugs identified in this computational analysis require in vitro and in vivo validation to confirm their effectiveness in POAG treatment. This may pave the way for understanding life-threatening disorders such as cancer.

• BMB Reports
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• v.50 no.2
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• pp.60-70
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• 2017

Glaucoma is characterized by a slow and progressive degeneration of the optic nerve, including retinal ganglion cell (RGC) axons in the optic nerve head (ONH), leading to visual impairment. Despite its high prevalence, the biological basis of glaucoma pathogenesis still is not yet fully understood, and the factors contributing to its progression are currently not well characterized. Intraocular pressure (IOP) is the only modifiable risk factor, and reduction of IOP is the standard treatment for glaucoma. However, lowering IOP itself is not always effective for preserving visual function in patients with primary open-angle glaucoma. The second messenger cyclic adenosine 3',5'-monophosphate (cAMP) regulates numerous biological processes in the central nervous system including the retina and the optic nerve. Although recent studies revealed that cAMP generated by adenylyl cyclases (ACs) is important in regulating aqueous humor dynamics in ocular tissues, such as the ciliary body and trabecular meshwork, as well as cell death and growth in the retina and optic nerve, the functional role and significance of cAMP in glaucoma remain to be elucidated. In this review, we will discuss the functional role of cAMP in aqueous humor dynamics and IOP regulation, and review the current medications, which are related to the cAMP signaling pathway, for glaucoma treatment. Also, we will further focus on cAMP signaling in RGC growth and regeneration by soluble AC as well as ONH astrocytes by transmembrane ACs to understand its potential role in the pathogenesis of glaucoma neurodegeneration.