Choi S.-I.,Corneal Dystrophy Research Institute |
Choi S.-I.,Yonsei University |
Kim K.S.,Duke University |
Oh J.-Y.,Corneal Dystrophy Research Institute |
And 7 more authors.
Journal of Pineal Research | Year: 2013
The hallmark of granular corneal dystrophy type 2 (GCD2) is the deposit of mutant transforming growth factor-β (TGF-β)-induced protein (TGFBIp) in the cornea. We have recently shown that there is a delay in autophagic degradation of mutant-TGFBIp via impaired autophagic flux in GCD2 corneal fibroblasts. We hypothesized that melatonin can specifically induce autophagy and consequently eliminate mutant-TGFBIp in GCD corneal fibroblasts. Our results show that melatonin activates autophagy in both wild-type (WT) and GCD2-homozygous (HO) corneal fibroblast cell lines via the mammalian target of rapamycin (mTOR)-dependent pathway. Melatonin treatment also led to increased levels of beclin 1, which is involved in autophagosome formation and maturation. Furthermore, melatonin significantly reduced the amounts of mutant- and WT-TGFBIp. Treatment with melatonin counteracted the autophagy-inhibitory effects of bafilomycin A1, a potent inhibitor of autophagic flux, demonstrating that melatonin enhances activation of autophagy and increases degradation of TGFBIp. Cotreatment with melatonin and rapamycin, an autophagy inducer, had an additive effect on mutant-TGFBIp clearance compared to treatment with either drug alone. Treatment with the selective melatonin receptor antagonist luzindole did not block melatonin-induced autophagy. Given its ability to activate autophagy, melatonin is a potential therapeutic agent for GCD2. © 2012 John Wiley & Sons A/S.
Maeng Y.-S.,Corneal Dystrophy Research Institute |
Maeng Y.-S.,Yonsei University |
Kwon J.Y.,Yonsei University |
Kim E.K.,Corneal Dystrophy Research Institute |
And 2 more authors.
Stem Cells | Year: 2015
As the ability to control the differentiation of endothelial stem/progenitor cells (EPCs) into vascular endothelial cell lineages could be useful for promoting neovascularization, it is important to obtain a deeper understanding of the epigenetic mechanisms that regulate EPC differentiation and neovascularization. Heterochromatin protein 1α (HP1α) is known to be involved in the epigenetic regulation of gene silencing. However, recent reports demonstrate that HP1α can also activate gene expression during cell differentiation. In this study, microarray analysis revealed that HP1α expression was induced during EPC differentiation and is associated with the expression of outgrowing endothelial cell (OEC)-specific protein markers. To explore the role of HP1α in the differentiation of EPCs to OECs, its expression was knocked-down or over-expressed in differentiating EPCs. Overexpression of HP1α promoted the differentiation and angiogenic activity of EPCs in vitro and in vivo, whereas knockdown of HP1α led to a defect in OEC migration, tube formation, and angiogenic sprouting activity. Gene expression profiling showed increased expression of angiogenic genes, including NOTCH1, cadherin-5, and angiopoietin-like-2, and decreased expression of progenitor cell marker genes, including CD133, CXCR4, and C-KIT, in HP1α-overexpressing EPCs. Also, increased HP1α at an early stage of EPC differentiation may regulate angiogenic gene transcription by interacting with chromatin that modifies epigenetic factors such as the methyl-CpG binding domain, Polycomb group ring finger 2, and DNA methyltransferases. Our findings demonstrate, for the first time, that HP1α plays an important role in the differentiation and angiogenic function of EPCs by regulating endothelial gene expression. Stem Cells 2015;33:1512-1522 © 2015 AlphaMed Press.
Lee H.,Yonsei University |
Lee K.,Yonsei University |
Ahn J.M.,Yonsei University |
Kim E.K.,Yonsei University |
And 3 more authors.
Optometry and Vision Science | Year: 2014
PURPOSE: To compare the optical quality measurements obtained from the double-pass system and ocular aberrations, subjective visual acuity, and contrast sensitivity score in pseudophakic eyes. Methods: Three months after cataract surgery, modulation transfer function (MTF) cutoff frequency, Strehl ratio, objective scatter index, and objective pseudoaccommodation obtained from the double-pass system were compared with total aberration, higher-order aberration, and spherical aberration obtained from ray-tracing aberrometer. In addition, parameters of the double-pass system were compared with subjective visual acuity and the contrast sensitivity score. RESULTS: Forty eyes of 40 patients were included. The MTF cutoff frequency and Strehl ratio were negatively correlated with total aberration (r = -0.503, p = 0.003; r = -0.509, p = 0.003, respectively) and subjective visual acuity (r = -0.453, p = 0.007; r = -0.354, p = 0.040, respectively). The objective scatter index was positively correlated with total aberration (r = 0.451, p = 0.024) and subjective visual acuity (r = 0.516, p = 0.008). The MTF cutoff frequency showed a correlation with contrast sensitivity score under photopic and mesopic conditions. CONCLUSIONS: Optical quality parameters obtained from the double-pass system were correlated with ocular aberrations, subjective visual acuity, and contrast sensitivity score in pseudophakic eyes. Copyright © 2014 American Academy of Optometry.
Han K.E.,Corneal Dystrophy Research Institute |
Han K.E.,Institute of Vision Research |
Kim C.Y.,Institute of Vision Research |
Chung J.L.,Konyang University |
And 6 more authors.
Journal of Cataract and Refractive Surgery | Year: 2012
A 57-year-old woman had concomitant surgery of persistent pupillary membrane removal and uneventful phacoemulsification through the same temporal clear corneal incision in her left eye. Short axial lengths (right eye, 21.08 mm; left eye, 20.39 mm) with shallow angles were noted bilaterally, and other findings were not remarkable. The patient experienced angle-closure attacks 3 and 7 months postoperatively. At the second angle-closure attack, diffuse epithelial ingrowth was observed. The epithelial ingrowth covered the intraocular lens surface in the interpupillary area, the iris surface surrounding the pupil, and the temporal anterior chamber angle, but did not reach the corneal endothelial incision. After observation of iris blanching with laser photocoagulation, argon laser photocoagulation was applied to the epithelium covering the iris and angle 7 times during the following month. The epithelial ingrowth was completely removed and did not recur during the 36-month follow-up. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. © 2012 ASCRS and ESCRS.
Ha B.J.,Siloam Eye Hospital |
Kim T.-I.,Corneal Dystrophy Research Institute |
Kim T.-I.,Yonsei University |
Choi S.-I.,Corneal Dystrophy Research Institute |
And 6 more authors.
Cornea | Year: 2010
Purpose: To evaluate the effect of mitomycin C (MMC) on the exacerbation of corneal opacity that occurs in patients with granular corneal dystrophy type II (GCD II) after refractive corneal surface ablation. Methods: Ten eyes of patients with GCD II who underwent refractive corneal surface ablation with MMC were compared with 10 eyes that were not treated with MMC. Best spectacle-corrected visual acuity, the degree of corneal opacity, and contrast sensitivity were evaluated at least 3 years after surgery. Corneal opacities were quantified using Pentacam densitometry maps. Results: No measured between-group value showed a statistically significant difference. Conclusion: Simultaneous application of MMC does not prevent exacerbation of GCD II after refractive corneal surface ablation. Copyright © 2010 by Lippincott Williams & Wilkins.
PubMed | Corneal Dystrophy Research Institute
Type: Journal Article | Journal: Stem cells (Dayton, Ohio) | Year: 2015
Endothelial progenitor cells (EPCs) in the circulatory system have been suggested to maintain vascular homeostasis and contribute to adult vascular regeneration and repair. These processes require that EPCs recognize the extracellular matrix (ECM), migrate, differentiate, and undergo tube morphogenesis. The ECM plays a critical role by providing biochemical and biophysical cues that regulate cellular behavior. Here, we tested the importance of transforming growth factor-beta-induced protein (TGFBIp) in regulation of the differentiation and angiogenic potential of human cord blood-derived EPCs (CD133(+) C-kit(+) Lin(-) cells). EPCs displayed increased endothelial differentiation when plated on TGFBIp compared to fibronectin. EPCs also exhibited increased adhesion and migration upon TGFBIp stimulation. Moreover, TGFBIp induced phosphorylation of the intracellular signaling molecules SRC, FAK, AKT, JNK, and ERK in EPCs. Using integrin-neutralizing antibodies, we showed that the effects of TGFBIp on EPCs are mediated by integrins 4 and 5. Furthermore, TGFBIp increased the adhesion, migration, and tube formation of CD34(+) mouse bone marrow stem cells in vitro. Gene expression analysis of EPCs plated on TGFBIp revealed that EPCs stimulated by TGFBIp exhibit increased expression of Notch ligands, such as delta-like 1 (DLL1) and Jagged1 (JAG1), through nuclear factor-kappa B signaling activation. Collectively, our findings demonstrate, for the first time, that locally generated TGFBIp at either wounds or tumor sites may contribute to differentiation and angiogenic function of EPCs by augmenting the recruitment of EPCs and regulating the expression of endothelial genes DLL1 and JAG1.