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Choi, Seung‐,Il,Dadakhujaev, Shorafidinkhuja,Ryu, Hyunmi,im Kim, Tae,Kim, Eung Kweon Blackwell Publishing Ltd 2011 Journal of pineal research Vol.51 No.1
<P><B>Abstract: </B> Considering that oxidative stress plays a role in corneal fibroblast degeneration during granular corneal dystrophy type 2 (GCD2) and melatonin is an effective antioxidant, we examined the ability of melatonin to protect against oxidative stress‐induced cell death of primary cultured normal and GCD2‐homozygous corneal fibroblasts. Melatonin treatment protected primary cultured normal and GCD2 corneal fibroblasts from paraquat (PQ)‐induced oxidative stress and caused increased expression levels of Cu/Zn‐superoxide dismutase (SOD1) and glutathione reductase (GR) in both types of cells. Interestingly, catalase expression increased in normal corneal fibroblasts, but decreased in GCD2 corneal fibroblasts after melatonin treatment. Melatonin also reduced the levels of intracellular reactive oxygen species and H<SUB>2</SUB>O<SUB>2</SUB> in both cell types. In addition, the selective melatonin receptor antagonist luzindole blocked melatonin‐induced expression of SOD1 and GR. The expression levels of melatonin receptors 1A (MT1) and 1B (MT2) were significantly higher in GCD2 corneal fibroblasts than in normal cells. These results suggest that increased expression of melatonin receptors may be involved in the defense mechanisms against oxidative stress in GCD2 corneal fibroblasts, and melatonin may have potential therapeutic implications for GCD2 treatment.</P>
Choi, S.i.,Lee, E.,Jeong, J.B.,Akuzum, B.,Maeng, Y.S.,Kim, T.i.,Kim, E.K. Academic Press 2016 Biochemical and biophysical research communication Vol.477 No.4
Granular corneal dystrophy type 2 (GCD2) is caused by a point mutation (R124H) in the transforming growth factor β-induced (TGFBI) gene. In GCD2 corneal fibroblasts, secretion of the accumulated mutant TGFBI-encoded protein (TGFBIp) is delayed via the endoplasmic reticulum (ER)/Golgi-dependent secretory pathway. However, ER stress as the pathogenic mechanism underlying GCD2 has not been fully characterized. The aim of this study was to confirm whether ER stress is linked to GCD2 pathogenesis and whether the chemical chaperone, 4-phenylbutyric acid (4-PBA), could be exploited as a therapy for GCD2. We found that the ER chaperone binding immunoglobulin protein (BiP) and the protein disulfide isomerase (PDI) were elevated in GCD2. Western bolt analysis also showed a significant increase in both the protein levels and the phosphorylation of the key ER stress kinases, inositol-requiring enzyme 1α (IRE1α) and double stranded RNA activated protein kinase (PKR)-like ER kinase, as well as in levels of their downstream targets, X box-binding protein 1 (XBP1) and activating transcription factor 4, respectively, in GCD2 corneal fibroblasts. GCD2 cells were found to be more susceptible to ER stress-induced cell death than were wild-type corneal fibroblasts. Treatment with 4-PBA considerably reduced the levels of BiP, IRE1α, and XBP1 in GCD2 cells; notably, 4-PBA treatment significantly reduced the levels of TGFBIp without change in TGFBI mRNA levels. In addition, TGFBIp levels were significantly reduced under ER stress and this reduction was considerably suppressed by the ubiquitin proteasome inhibitor MG132, indicating TGFBIp degradation via the ER-associated degradation pathway. Treatment with 4-PBA not only protected against the GCD2 cell death induced by ER stress but also significantly suppressed the MG132-mediated increase in TGFBIp levels under ER stress. Together, these results suggest that ER stress might comprise an important factor in GCD2 pathophysiology and that the effects of 4-PBA treatment might have important implications for the development of GCD2 therapeutics.
인간 각막세포에서 국소 면역억제 인자 Indoleamine 2,3-dioxygenase의 발현
류양환,김재찬,Yang Hwan Ryu,M,S,Jae Chan Kim 대한안과학회 2007 대한안과학회지 Vol.48 No.8
Purpose: To identify the localization of indoleamine 2,3-dioxygenase (IDO) in human corneal cells and to evaluate its ability to act as a local immunosuppressive factor. Methods: The expression profile of IDO was obtained with RT-PCR and Western blot of in a primary culture of human corneal cells (fibroblasts, epithelial cells and endothelial cells). In order to investigate the immunosuppressive function of IDO, immune cells were cultured in a human corneal cell-conditioned medium, and their prolifleration was identified by the MTT assay. Moreover, apoptotic effects of IDO in immune cells treated with IFN-γ were also investigated with apoptosis ELISA. Results: Among the three different types of human corneal cells analyzed, mRNA and protein expression of IDO was observed only in human corneal fibroblasts. Immune cells cultured in a human corneal fibroblast-conditioned medium showed inhibited proliferation. Moreover, IFN-γ-induced expression of IDO significantly enhanced apoptotic ability in a dose-depandant manner. Conclusions: Our results suggest that human corneal fibroblasts are relatively immuno-resistant and that expression of IDO may be one of the factors involved in the immune tolerance observed in corneal grafts.
Chung, Sung-Kun,Lee, Ja-Young,Joo, Choun-Ki,Kim, Jae-Ho 가톨릭대학교 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-
Farnesyl transferase inhibitors (FTI) disrupt fanesylation of ras protein and thus, suppress tumor growth in vivo, To determine whether FTI extracted from Cinnamomum Cassia Blume (CB2'-ph) interferes with angiogenesis, we studied the effect of CB2'-ph on rabbit corneal angiogenesis induced by basic fibroblast growth factor (bFGF). A hydrogel disk containing 1000ng of bFGF was implanted intrastromally in the superior cornea of 12 NZW rabbit eyes. All eyes received a second intrastromal disk, randomized to contain either 40㎍ of CB2'-ph(n=6) or phosphate-buffered saline (PBS) (n=6). Both disks were positioned side-by-side, 1.2mm from the superior limbus. Each eye was examined daily by two masked of new blood vessels. At 3, 5, and 7 days postimplantation of bFGF disks, eyes treated with CB2'-ph showed mean angiogenesis score of 6.0 ± 4.8, 25.6 ± 23.9 and 38.1 ± 28.3, respectively, while PBS-treated controls scored 10.4 ± 9.2, 27.2 ± 16.7, and 39.0 ± 22.8, respectively (p>0.4, Wilcoxon signed rank test). In a rabbit corneal pocket assay, CB2'-ph appears to be ineffective against bFGF-induced corneal angiogenesis in the model. (Journal of Korean Ophthalmology Society 40:657-661, 1999)
Treatment of descemetocele with combined deep keratotomy with a nictitating membrane flap in a dog
Manbok Jeong 대한수의학회 2023 大韓獸醫學會誌 Vol.63 No.2
A 10-year-old, spayed female, Maltese dog presented with a 2-day history of severe left eye squint. Slit-lamp biomicroscopy showed a deep corneal defect stained into a doughnut shape together with hypopyon in the anterior chamber. Based on these results, a diagnosis of descemetocele and uveitis in the left eye was made. Deep keratotomy combined with a nictitating membrane flap effectively resolved the descemetocele without complications. The surgical procedures performed on this patient were easy and effective, and could be used as an alternative to graft surgery for descemetocele treatment.