-
[show abstract]
[hide abstract]
ABSTRACT: Optic neuropathy including glaucoma is one of the leading causes of irreversible vision loss, and there are currently no effective therapies. The hallmark of pathophysiology of optic neuropathy is oxidative stress and apoptotic death of retinal ganglion cells (RGCs), a population of neurons in the central nervous system with their soma in the inner retina and axons in the optic nerve. We here tested that an anti-apoptotic protein stanniocalcin-1 (STC-1) can prevent loss of RGCs in the rat retina with optic nerve transection (ONT) and in cultures of RGC-5 cells with CoCl2 injury. We found that intravitreal injection of STC-1 increased the number of RGCs in the retina at days 7 and 14 after ONT, and decreased apoptosis and oxidative damage. In cultures, treatment with STC-1 dose-dependently increased cell viability, and decreased apoptosis and levels of reactive oxygen species in RGC-5 cells that were exposed to CoCl2. The expression of HIF-1α that was up-regulated by injury was significantly suppressed in the retina and in RGC-5 cells by STC-1 treatment. The results suggested that intravitreal injection of STC-1 might be a useful therapy for optic nerve diseases in which RGCs undergo apoptosis through oxidative stress.
PLoS ONE 01/2013; 8(5):e63749. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the association between dry eye syndrome (DE) and serum levels of interleukin (IL)-17 in patients with systemic immune-mediated diseases.
IL-17 and IL-23 levels were measured in the sera of patients whose tear production was <5 mm on the Schirmer test. Subjects included patients with chronic graft-versus-host disease (GVHD), rheumatoid arthritis (RA), Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), and no systemic disease. Corneal/conjunctival fluorescein staining was scored and the correlation between the score and the IL-17 level was evaluated.
A strong correlation existed between IL-17 level and the type of systemic disease. IL-17 was significantly elevated in patients with chronic GVHD compared to those with RA and SS. IL-17 was not detectable in patients with SLE or in those without systemic disease. IL-23 was not detected in any of the subjects. IL-17 was significantly increased in patients with high fluorescein staining scores.
Our data suggest that IL-17 is involved in the pathogenesis of DE in patients with systemic immune-mediated diseases.
Korean Journal of Ophthalmology 04/2011; 25(2):73-6.
-
Japanese Journal of Ophthalmology 01/2011; 55(1):70-1. · 0.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the clinical features, associated factors, and treatment outcomes of scleritis in the Korean population.
Medical records were retrospectively reviewed for 94 eyes of 76 patients with scleritis. Clinical features of scleritis, including systemic disease, presence of microorganisms, serologic markers, history of previous ocular surgery, and use of immunosuppressants were investigated and compared amongst the subtypes of scleritis. Treatment outcomes were evaluated using best corrected visual acuity (BCVA) and time to scleritis remission.
Nodular scleritis was the most common form observed, followed by necrotizing scleritis with inflammation, diffuse scleritis, and necrotizing scleritis without inflammation, respectively. A total of 16 of 76 patients (21.1%) had connective tissue diseases. Eleven cases (14.5%) had infectious scleritis, of which bacteria (54.5%) and fungi (45.5%) were the causative microorganisms. Thirty-three patients (43.4%) had previous ocular surgery, mostly pterygium excision. Notably, a history of pterygium excision was significantly associated with development of necrotizing and infectious scleritis (odds ratio [OR], 399 and 10.1; p < 0.001 and 0.002, respectively). In addition, patients with necrotizing scleritis were more likely to have infectious scleritis (OR, 11.7; p = 0.001). BCVA after treatment and time to remission also showed significant differences among the different scleritis subtypes. Systemic immunosuppression was required in addition to steroids for treating diffuse and necrotizing scleritis.
Careful taking of patient history including previous pterygium excision should be performed, especially in patients with necrotizing and infectious scleritis. In addition, evaluation of microbiological infection can be crucial for patients with necrotizing scleritis and history of pterygium excision.
Korean Journal of Ophthalmology 12/2010; 24(6):331-5.
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the effect of ex vivo culture on the expression of human leukocyte antigen (HLA) in human corneal limbal epithelial cells (LECs), and to evaluate the expression of HLA and costimulatory molecules on human corneal limbal stromal cells (LSCs).
The expression of HLA-ABC and HLA-DR were evaluated using flow cytometry on cultured human LECs and LSCs after serial passage and compared with that on freshly isolated cells. Additionally, the expression of costimulatory molecules CD80, CD86, CD40, and immunoregulatory molecule HLA-G were investigated on LSCs with or without an addition of interferon (IFN) γ (250 U/mL, 4 days).
HLA-ABC and HLA-DR were expressed in 99.12 ± 1.02% and 25.86 ± 4.34% of freshly isolated LECs, respectively. After culture, the HLA-DR-expressing cells significantly decreased with serial passage, whereas the percentage of HLA-ABC-expressing cells did not change. More than 90% of LSCs expressed HLA-ABC and HLA-G, whereas the expression of HLA-DR, CD80, CD86, and CD40 was negligible. This expression profile did not change after serial passage. However, the treatment with IFN-γ induced a significant increase in HLA-DR (0.17% vs. 17.68%) and CD40 (0.19% vs. 13.19%) expression on LSCs.
The immunogenicity of LECs can be lowered after ex vivo cultivation, whereas LSCs can be immunogenic in the presence of IFN-γ.
Cornea 11/2010; 29(11):1302-7. · 1.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate corneal biomechanical properties in eyes that had previously undergone penetrating keratoplasty (PK) using the ocular response analyzer (ORA).
We recruited 26 patients who had received unilateral PK. Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and cornea-compensated intraocular pressure (IOPcc) were measured with the ORA and were compared to the measurements from the contralateral eyes that did not undergo PK.
The CH was 8.95+/-2.59 mmHg in eyes that underwent PK and 9.78+/-1.45 mmHg in the contralateral eyes that did not undergo PK (p=0.077). The CRF was 10.26+/-2.64 mmHg in post-PK eyes and 9.75+/-1.45 mmHg in the contralateral eyes (p=0.509), and the CH-CRF was significantly smaller in post-PK eyes (-1.31+/-2.32 mmHg in post-PK eyes vs. 0.03+/-0.88 mmHg in fellow eyes, p=0.016). The IOPg and IOPcc were significantly higher in the PK group than they were in the control group. The IOPcc's were 20.81+/-7.81 mmHg and 16.27+/-2.49 mmHg in post-PK and control eyes, respectively (p=0.011); and the IOPg's were 19.22+/-7.34 mmHg and 15.07+/-3.03 mmHg in post-PK and control eyes, respectively (p=0.019). The IOPcc-g's were 1.59+/-2.81 mmHg and 1.21+/-1.30 mmHg in post-PK and control eyes, respectively (p=0.412), and the central corneal thickness (CCT)'s were 489.11+/-90.60 microm and 556.24+/-42.84 microm in post-PK and control eyes, respectively (p=0.068).
Following PK, CH tended to decrease while CRF tended to increase, significantly decreasing CH-CRF. A significantly higher intraocular pressure and a thinner CCT following PK may have contributed to the observed changes in these corneal biomechanical parameters.
Korean Journal of Ophthalmology 06/2010; 24(3):139-42.
-
[show abstract]
[hide abstract]
ABSTRACT: A 68-year-old woman presented with pain in her left eye. Necrosis with calcium plaques was observed on the medial part of the sclera. Aspergillus fumigatus was isolated from the culture of the necrotic area. On systemic work-up including serum and urine electrophoresis studies, the serum monoclonal protein of immunoglobulin G was detected. The patient was diagnosed with monoclonal gammopathy of undetermined significance and fungal scleritis. Despite intensive treatment with topical and oral antifungal agents, scleral inflammation and ulceration progressed, and scleral perforation and endophthalmitis developed. Debridement, antifungal irrigation, and tectonic scleral grafting were performed. The patient underwent a combined pars plana vitrectomy with an intravitreal injection of an antifungal agent. However, scleral and intraocular inflammation progressed, and the eye was enucleated. Aspergillus fumigatus was isolated from the cultures of the eviscerated materials. Giemsa staining of the excised sclera showed numerous fungal hyphae.
Korean Journal of Ophthalmology 06/2010; 24(3):175-8.
-
[show abstract]
[hide abstract]
ABSTRACT: Keratoconus and choroidal neovascularization can occur as a result of dysfunction of the epithelium and its basement membrane.
A 17-year-old Asian man, who was diagnosed with myopic choroidal neovascularization in both eyes and who subsequently underwent intravitreal injection of ranibizumab (Lucentis(R)) five times over six months, presented with further vision decrease and pain in his right eye. Examination showed corneal steepening and stromal edema in the inferocentral cornea of his right eye, both of which were indicative of advanced keratoconus with acute hydrops. Corneal topography also showed features consistent with keratoconus in his left eye. Fluorescein angiography and optical coherence tomography revealed choroidal neovascularization-associated subretinal hemorrhages and lacquer cracks in both eyes.
Keratoconus and choroidal neovascularization, possibly resulting from dysfunction of the epithelium and its basement membrane, can occur together in the same individual. This would suggest a possible connection in pathogenesis between these two conditions.
Journal of Medical Case Reports 02/2010; 4:58.
-
[show abstract]
[hide abstract]
ABSTRACT: Joo Youn Oh1,2, Hyun Ju Lee1,2, Sang In Khwarg1,2, Won Ryang Wee1,21Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea; 2Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul, KoreaPurpose: Although cryotherapy has long been used to eradicate corneal lesions, there have been no reports of adverse effects of cryotherapy on human corneas. We performed this study to evaluate and characterize ultrastructural damage to the human cornea following the transcorneal freezing-and-thawing procedure.Methods: Seven human donor corneas were randomly divided into three groups. 1, 2, and 3 repetitive freezing-and-thawing procedures were respectively applied to donor corneas in each group. A cryoprobe was cooled to -80°C, and placed on the anterior surface 1.5 mm central to the limbus for 3 seconds. Samples were then allowed to spontaneously defrost. A cornea without the treatment was used as a control. Samples were evaluated through hematoxylin & eosin staining, TUNEL assay, and electron microscopy.Results: After transcorneal cryoinjury, it was observed that corneal endothelial cells were lost and Descemet’s membrane was denuded where the cryoprobe was applied. Corneal stromal cells were damaged, and the damage was more marked in the posterior stroma. The extent of damage increased with an increasing number of freezing–thawing repetitions. In contrast, corneal epithelial cells showed no cryo-induced damage, and Bowman’s layer remained intact in all groups.Conclusions: The susceptibility to transcorneal cryo-injury differed among the corneal layers; the corneal endothelium was most susceptible, and the epithelium was least susceptible. Caution would thus be advised in regard to the potential damage in corneal endothelium when treating patients with corneal lesions using transcorneal cryotherapy.Keywords: apoptosis, cryotherapy, endothelium, keratocyte
Clinical Ophthalmology. 01/2010;
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the effect of pterygium surgery on corneal topography and contrast sensitivity.
The IRB approved this prospective, nonrandomized, self-controlled study. Computerized videokeratography (Orbscan II) was performed in 36 patients with primary pterygia, both before and 1 month after pterygium excision with limbal-conjunctival autografting. The topographic parameters were compared. Spatial contrast sensitivity testing was performed using VCTS 6500. Differences between preoperative and postoperative values were evaluated statistically.
The mean Sim K astigmatism and irregularity index, significantly decreased after pterygium surgery. The mean refractive power significantly increased after the operation. The "with-the-rule" astigmatism induced by pterygium became "against-the-rule" astigmatism after pterygium removal (P = 0.041). The contrast sensitivity of 6, 12, and 18 cycles per degree, significantly increased from 1.55 +/- 0.28, 0.97 +/- 0.47, and 0.29 +/- 0.16 to 1.72 +/- 0.18, 1.21 +/- 0.44, and 0.65 +/- 0.48, respectively (P = 0.007, <0.001, <0.001, respectively).
Pterygium surgery significantly reduces corneal topographic astigmatism and improves contrast sensitivity.
Clinical Ophthalmology 01/2010; 4:315-9.
-
[show abstract]
[hide abstract]
ABSTRACT: Although cryotherapy has long been used to eradicate corneal lesions, there have been no reports of adverse effects of cryotherapy on human corneas. We performed this study to evaluate and characterize ultrastructural damage to the human cornea following the transcorneal freezing-and-thawing procedure.
Seven human donor corneas were randomly divided into three groups. 1, 2, and 3 repetitive freezing-and-thawing procedures were respectively applied to donor corneas in each group. A cryoprobe was cooled to - 80 degrees C, and placed on the anterior surface 1.5 mm central to the limbus for 3 seconds. Samples were then allowed to spontaneously defrost. A cornea without the treatment was used as a control. Samples were evaluated through hematoxylin & eosin staining, TUNEL assay, and electron microscopy.
After transcorneal cryoinjury, it was observed that corneal endothelial cells were lost and Descemet's membrane was denuded where the cryoprobe was applied. Corneal stromal cells were damaged, and the damage was more marked in the posterior stroma. The extent of damage increased with an increasing number of freezing-thawing repetitions. In contrast, corneal epithelial cells showed no cryo-induced damage, and Bowman's layer remained intact in all groups.
The susceptibility to transcorneal cryo-injury differed among the corneal layers; the corneal endothelium was most susceptible, and the epithelium was least susceptible. Caution would thus be advised in regard to the potential damage in corneal endothelium when treating patients with corneal lesions using transcorneal cryotherapy.
Clinical Ophthalmology 01/2010; 4:477-80.
-
Japanese Journal of Ophthalmology 11/2009; 53(6):653-5. · 0.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the expression of alpha-Gal or unidentified non-Gal antigens in pig corneal endothelial cells and keratocytes, we performed the qualitative and quantitative analysis by using mass spectrometry.
The N-glycans from common adult pig corneal endothelial cells and keratocytes cultured in vitro were directly analyzed by using mass spectrometric approaches. In addition, immunochemical staining was added to confirm the non-Gal antigen expression in pig corneal cells.
Totally, 34 of the sialylated N-glycans from pig corneal endothelial cells and 27 from pig keratocytes were identified and observed to contain nonhuman sialic acid, NeuGc as well as NeuAc. In addition, we were able to detect 25 of alpha-galactosylated N-glycan structures (22.2% of total) from the pig corneal endothelial cells and 18 of that (17.5% of total) from the pig keratocytes by using mass spectrometric approaches. On immunofluorescent staining, the expression of sialylated glycans was also observed.
As well as alpha-Gal epitopes, several promising non-Gal antigens were widely expressed on both pig corneal endothelial cells and keratocytes. The detailed structural information of the alpha-Gal and non-Gal epitopes would be a tremendous value to develop a new strategy for the successful corneal xenotransplantation in future.
Current eye research 10/2009; 34(10):877-95. · 1.51 Impact Factor
-
Japanese Journal of Ophthalmology 09/2009; 53(5):551-3. · 0.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We designed a randomized, double blinded, 3-months controlled prospective clinical study to investigate effects of oral uridine on the ocular surface in dry eye patients. Twenty-seven patients who diagnosed as dry eye with lower than 5 mm of wetting in the Schirmer strip, with corneal epithelial erosion and who completely followed-up till 3 months were enrolled. Corneal-conjunctival fluorescein staining, non-anesthetic Schirmer test, impression cytology, and Ocular Surface Disease Index (OSDI) were evaluated in the experimental and placebo groups at the baseline, 1 and 3 months after start of medication in a double blinded manner. Fluorescein stain score of the cornea was markedly decreased in oral uridine group compared to the placebo group at 3 months after medication (P=0.032, Mann-Whitney U test). The Schirmer wetting score for the oral uridine group was significantly increased (P=0.001, Wilcoxon signed rank test) at 3 months and its difference between two groups was statistically significant (P=0.030, Mann-Whitney U test). OSDI scores were significantly decreased at 1 and 3 months in treatment group. Oral uridine is effective in treatment of dry eyes.
Journal of Korean medical science 09/2009; 24(4):701-7. · 0.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the change of tissue inhibitor of metalloproteinase (TIMP) in cryopreserved amniotic membranes (AM) according to preservation time, and to evaluate the expression of TIMP in freeze-dried AM.
Cryopreserved or fresh AMs were incubated in dispase II for two hours at 37 degrees C and their epithelial cells were scraped with a cell scraper. Remaining stromal AM was minced and frozen in liquid nitrogen, and then treated with 0.1% diethyl pyrocarbonate. The mRNA levels of TIMP-1 and -2 were determined by reverse transcription-polymerase chain reaction (RT-PCR) in epithelial and stromal cells of fresh AM, AMs cryopreserved for 6 and 12 months, and freeze dried AM, respectively. Western blot analysis and immunohistochemical staining were performed to assess the expression of TIMP-1 in fresh, cryopreserved, and freeze dried AMs.
RT-PCR revealed that mRNAs of TIMP-1 and -2 were expressed in the amniotic epithelial cells of both fresh and cryopreserved AMs, while the stromal cells of fresh or cryopreseved AMs and freeze-dried AM showed higher expression of TIMP-1 than TIMP-2 mRNA. On Western blot analysis, the level of TIMP-1 was more in fresh AMs than in cryopreserved or freeze-dried AM, but it was not statistically significant.
TIMP-1 was expressed in cryopreserved AMs until 12 months, and the amount of expression was comparable to that in fresh AMs.
Current Eye Research 07/2009; 32(7-8):611-6. · 1.28 Impact Factor
-
Japanese Journal of Ophthalmology 06/2009; 53(3):286-7. · 0.92 Impact Factor
-
Mee Kum Kim, Joo Youn Oh,
Jung Hwa Ko,
Hyun Ju Lee,
Jin Ho Jung,
Won Ryang Wee,
Jin Hak Lee,
Chung-Gyu Park,
Sang Joon Kim,
Curie Ahn,
Seung-Jun Kim,
Seung Yong Hwang
[show abstract]
[hide abstract]
ABSTRACT: Porcine to rat corneal xenotransplantation resulted in severe inflammation and rejection of the corneal stroma, whereas an allograft showed mainly endothelial cell-associated rejection. We, therefore, investigated and compared the gene expression between porcine keratocytes and corneal endothelial cells. RNA was isolated from primary cultured porcine or human keratocytes and porcine corneal endothelial cells. Gene expression was comparatively analyzed after normalization with microarray method using Platinum pig 13 K oligo chip (GenoCheck Co., Ltd., Ansan, Korea). Real-time polymerase chain reaction (PCR) was performed for C1R, CCL2, CXCL6, and HLA-A in porcine keratocytes and corneal endothelial cells. As a result, upregulated expression more than 2 folds was observed in 1,162 genes of porcine keratocytes versus porcine endothelial cells. Among the immune-regulatory genes, SEMA3C, CCL2, CXCL6, F3, HLA-A, CD97, IFI30, C1R, and G1P3 were highly expressed in porcine keratocytes, compared to porcine corneal endothelial cells or human keratocytes. When measured by real-time PCR, the expression of C1R, CCL2, and HLA-A was higher in porcine keratocytes compared to that in porcine corneal endothelial cells. In conclusion, the increased expression of C1R, CCL2, and HLA-A genes in porcine keratocytes might be responsible for the stromal rejection observed in a porcine to rat corneal xenotransplantation.
Journal of Korean medical science 05/2009; 24(2):189-96. · 0.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the role of T cells and natural killer (NK) cells in mediating corneal xenograft rejection in a pig-to-mouse model.
Pig corneas were orthotopically transplanted into BALB/c, C57BL/6, nude, severe combined immunodeficiency (SCID), and NOD/SCID/gammac(null) (NOG) mice. Graft survival was clinically assessed by slit-lamp biomicroscopy and median survival times (MST) were calculated. The rejected grafts were histologically evaluated using antibodies against CD4, CD8, NK1.1, and F4/80.
The pig corneal xenografts were acutely rejected by BALB/c and C57BL/6 mice (MST 9.0 days), while nude, SCID and NOG mice rejected pig corneas in a more delayed fashion (MST 16.0, 16.4, and 16.9 days, respectively). The majority of infiltrating cells found in rejected grafts in C57BL/6 mice were macrophages and CD4(+) T cells, while CD8(+) T cells and NK cells were rarely found. The grafts in nude mice had markedly decreased inflammatory infiltration with small numbers of macrophages and CD4(+) T cells. Infiltration was even more modest in grafts in SCID and NOG mice.
T cells play an important role in acute rejection of pig corneal xenografts in mice, although acute rejection is not solely the result of T-cell-mediated immunity. NK cells are less likely to be involved in the rejection process.
Xenotransplantation 04/2009; 16(2):74-82. · 2.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the effect of bevacizumab in a model of corneal inflammation.
Epithelium from the cornea and limbus was completely removed using 100% alcohol in rats. Bevacizumab (1.25 mg/0.05 ml) or normal saline was subconjunctivally injected. One week later, corneas were examined and subjected to hematoxylin-eosin and immunofluorescent staining for VEGF. Expression of IL-2, IFN-gamma, IL-6, and TGF-beta 1 were analyzed by ELISA.
Bevacizumab showed a borderline reduction in corneal neovascularization (11.0 +/- 4.8% and 18.0 +/- 10.0% in the bevacizumab and control groups, respectively; p = 0.054), while the extent of epithelialization was not affected (5.0 +/- 3.4% and 6.1 +/- 5.2% in the bevacizumab and control groups, respectively; p = 0.715). The infiltration of inflammatory cells was reduced (99.3 +/- 22.3 cells/x 400 in the bevacizumab-injected corneas and 182.3 +/- 58.0 cells/x 400 in the controls; p = 0.013). The levels of IL-2, IFN-gamma, and IL-6 were decreased in the rats with the bevacizumab injections (44 +/- 6 and 79 +/- 9 pg/ml for IL-2 in the bevacizumab-injected group and control, respectively, p = 0.025; 45 +/- 5 and 67 +/- 6 pg/ml for IFN-gamma in the bevacizumab-injected group and controls, respectively, p = 0.043; 45 +/- 6 and 75 +/- 8 pg/ml for IL-6 in the bevacizumab-injected group and controls, respectively, p = 0.030).
Bevacizumab showed a reduction in inflammatory cell infiltration and cytokines in chemically burned rat corneas.
Current eye research 03/2009; 34(2):85-91. · 1.51 Impact Factor
