Development of eye phantom for mimicking the deformation of the human cornea accompanied by intraocular pressure alterations.

Comparative studies between artificial eyeball phantoms and in-vivo human subjects were carried out to better understanding the structural deformation of the cornea under varying intraocular pressure (IOP). The IOP-induced deformation and the tension of the cornea were measured by using an optical coherence tomography and noncontact tonometer readings, respectively. The dependence of the central cornea thickness (CCT) and corneal radius of curvature (CRC) on the IOP differed significantly between the full eyeball phantom (FEP) and cornea eyeball phantom (CEP) models. While the CCT changes were very similar between the two models, the relation between the CRC and the IOP was dependent on the type of eye phantom. For the CEP, the CRC drastically decreased as internal pressure increased. However, we found that the changes in the CRC of FEP was dependent on initial CCT under zero IOP (CCT0). When CCT0 was less than 460 µm, the CRC slightly decreased as IOP increased. Meanwhile, the CRC increased as IOP increased if CCT0 was 570 µm. A constitutive mechanical model was proposed to describe the response of the cornea accompanied by the changes in IOP. In vivo measurements on human subjects under both noninvasive and invasive conditions revealed that the relation between the CRC on the IOP is much closer to those observed from FEP. Considering the observed structural deformation of human cornea, we found that FEP mimics the human eye more accurately than the CEP. In addition, the tonometry readings of IOP show that the values from the CEP were overestimated, while those from the FEP were not. For these reasons, we expect that the FEP could be suitable for the estimation of true IOP and allow performance testing of tonometers for medical checkups and other clinical uses.

Pathogenic Risk Factors and Associated Outcomes in the Bullous Variant of Central Serous Chorioretinopathy.

PURPOSE: To compare the clinical features, treatments, and outcomes between bullous and chronic variants of central serous chorioretinopathy (CSC). DESIGN: Retrospective, observational case series. PARTICIPANTS: Sixty-two eyes of 44 patients with bullous-variant CSC (bvCSC) and 97 eyes of 85 patients with nonbullous CSC. METHODS: We conducted a national survey between September 1, 2020, and March 31, 2021, of members of the Korean Retina Society and obtained data of patients with bvCSC from 11 retinal centers. A comparator group comprised consecutive chronic CSC patients without bullous detachment. MAIN OUTCOME MEASURES: Baseline demographics and patient characteristics were compared between groups. Secondary outcomes included factors associated with visual prognosis within the bvCSC group. RESULTS: Compared with the nonbullous CSC group, the bvCSC group presented at a younger age (49 vs. 52 years; P = 0.047) and with more bilateral involvement (41% vs. 14%; P < 0.001). Systemic corticosteroid use was more prevalent in the bvCSC group, both in terms of any exposure (50% vs. 20%; P = 0.001) and long-term exposure (36% vs. 9%; P < 0.001). The bvCSC group had distinct imaging features (all P < 0.05): retinal folding (64% vs. 1%), subretinal fibrin (75% vs. 13%), multiple retinal pigment epithelium tears (24% vs. 2%), and multifocal fluorescein leakages with terminal telangiectasia (36% vs. 1%). Although bvCSC patients had worse vision at diagnosis (20/80 vs. 20/44; P = 0.003), treatment response was more robust (fluid resolution by final follow-up, 84% vs. 68%; P = 0.034) even with conservative management, resulting in similar final vision (20/52 vs. 20/45; P = 0.52). History of kidney-related (odds ratio [OR] 5.4; 95% confidence interval [CI] 1.3-18.5; P = 0.045) and autoimmune/rheumatoid diseases (OR 25.4, 95% CI 2.8-195.0; P = 0.004) showed associations with the bvCSC group. Apart from vision at diagnosis (OR 0.1, 95% CI 0.05-0.36; P < 0.001), a history of renal transplantation was most predictive of visual prognoses for bvCSC eyes (OR 0.2, 95% CI 0.04-0.75; P = 0.020). CONCLUSIONS: Bullous-variant CSC may be associated with pathogenic risk factors based on underlying medical conditions and systemic corticosteroid use. Poor vision at diagnosis and history of renal transplantation were associated with poor visual outcome.

Safety and Efficacy of Selective Intra-arterial Thrombolysis for Central Retinal Artery Occlusion.

PURPOSE: The purpose of this study was to determine the efficacy and safety of selective intra-arterial thrombolysis in patients with central retinal artery occlusion (CRAO). METHODS: Medical records for 44 eyes of 44 patients diagnosed with acute non-arteritic CRAO and thrombolysis between October 2010 and February 2019 were analyzed retrospectively. Based on visual acuity, fundoscopic findings, and fluorescein angiography, the patients were classified into three stages: incomplete, subtotal, and total. The perfusion state using the best-corrected visual acuity (BCVA), arm to retina time, and arteriovenous passage times, after 1 month, 6 months, and at the final visit after the procedure, were compared with baseline readings. RESULTS: Improvement of visual acuity was confirmed in 31 out of 44 patients (70.45%). The mean BCVA of 44 patients changed from 1.65 ± 0.78 logarithmic minimum angle of resolution (logMAR) at the first visit to 1.18 ± 0.91 logMAR at the last visit (p = 0.114). The BCVA according to CRAO stage was 0.08 ± 0.11 logMAR for the incomplete stage at the first visit, 0.06 ± 0.05 logMAR (p = 0.933) 1 month after the procedure, and 0.05 ± 0.07 logMAR (p = 0.933) at the last visit. In the subtotal stage, the results were 1.81 ± 0.54 logMAR at the first visit, 1.63 ± 0.76 logMAR (p = 0.035) 1 month after the procedure, and 1.36 ± 0.85 logMAR (p = 0.014) at the last visit. For the total stage of BCVA, the result at the first visit was 2.36 ± 0.25 logMAR, and it was 2.30 ± 0.30 logMAR (p = 0.510) 1 month after the procedure, and 2.42 ± 0.30 logMAR (p = 0.642) at the last visit. Reperfusion was observed in 40 patients out of the 44 (90.91%). CONCLUSIONS: Selective intra-arterial thrombolysis can be helpful in patients with subtotal CRAO in terms of visual improvement and retinal arterial reperfusion.

Prospective, Single-Center, Six-Month Study of Intravitreal Ranibizumab for Macular Edema with Nonproliferative Diabetic Retinopathy: Effects on Microaneurysm Turnover and Non-Perfused Retinal Area.

PURPOSE: To analyze the effects on microaneurysm (MA) and perifoveal perfusion in nonproliferative diabetic retinopathy (NPDR) patients with macular edema (ME) after early intensive treatment using intravitreal ranibizumab (IVR) injections. PATIENTS AND METHODS: Prospectively, 25 eyes of 25 type 2 diabetes mellitus patients with ME were included between August 2016 and February 2019. For 6 months, patients were administered 0.5-mg IVR injections monthly. Ocular evaluation, including best-corrected visual acuity (BCVA; using the Early Treatment Diabetic Retinopathy Study chart), central retinal thickness (CRT; using optical coherence tomography), fundus photography, and fluorescein angiography, was performed for all participants. Results obtained at baseline were compared to those observed after 6 months. RESULTS: Mean BCVA increased significantly from 67.6±3.29 letters at baseline to 76.36±1.61 letters after 6 months (P=0.002) of IVR therapy. CRT decreased significantly from 479.12±16.66 µm at baseline to 369.12±13.02 µm at 6 months. Similarly, the total number of MAs decreased significantly from 5.68±3.41 to 1.60±1.73 (P<0.0001). MA turnover, calculated by adding the MA formation rate to the MA disappearance rate (both calculated as MA number/month) also decreased significantly from 6.88±3.83 to 1.92±1.75 after treatment (P<0.0001). Perifoveal non-perfused area decreased from 2.517±0.456 mm2 at baseline to 2.495±0.293 mm2 at 6 months, but the results were not statistically significant (P=0.954). CONCLUSION: Treatment with early intensive IVR therapy in NPDR patients with ME not only improved BCVA and CRT but also decreased MA turnover. However, in the study period of 6 months, IVR therapy did not show significant improvement in perifoveal non-perfused area.

Lateral geniculate body evoked potentials elicited by visual and electrical stimulation.

PURPOSE: Blind individuals who have photoreceptor loss are known to perceive phosphenes with electrical stimulation of their remaining retinal ganglion cells. We proposed that implantable lateral geniculate body (LGB) stimulus electrode arrays could be used to generate phosphene vision. We attempted to refine the basic reference of the electrical evoked potentials (EEPs) elicited by microelectrical stimulations of the optic nerve, optic tract and LGB of a domestic pig, and then compared it to visual evoked potentials (VEPs) elicited by short-flash stimuli. METHODS: For visual function measurement, VEPs in response to short-flash stimuli on the left eye of the domestic pig were assessed over the visual cortex at position Oz with the reference electrode at Fz. After anesthesia, linearly configured platinum wire electrodes were inserted into the optic nerve, optic track and LGB. To determine the optimal stimulus current, EEPs were recorded repeatedly with controlling the pulse and power. The threshold of current and charge density to elicit EEPs at 0.3 ms pulse duration was about ±10 µA. RESULTS: Our experimental results showed that visual cortex activity can be effectively evoked by stimulation of the optic nerve, optic tract and LGB using penetrating electrodes. The latency of P1 was more shortened as the electrical stimulation was closer to LGB. The EEPs of two-channel in the visual cortex demonstrated a similar pattern with stimulation of different spots of the stimulating electrodes. We found that the LGB-stimulated EEP pattern was very similar to the simultaneously generated VEP on the control side, although implicit time deferred. CONCLUSIONS: EEPs and VEPs derived from visual-system stimulation were compared. The LGB-stimulated EEP wave demonstrated a similar pattern to the VEP waveform except implicit time, indicating prosthetic-based electrical stimulation of the LGB could be utilized for the blind to perceive vision of phosphenes.

Outcome and significance of silicone oil tamponade in patients with chronic serous retinal detachment.

PURPOSE: To evaluate the effectiveness of silicone oil tamponade in patients with chronic serous retinal detachment (SRD) persisting for three months after the resolution of ocular inflammation. METHODS: A total of 17 eyes of 17 patients diagnosed with chronic SRD persisting for three months after the resolution of ocular inflammation and with high risk of phthisis bulbi by secondary ocular hypotony and macular detachment by subretinal fibrous membrane formation were subjected to surgical intervention. Subjects underwent silicone oil tamponade after surgical drainage of subretinal fluid. Retrospective analyses on anatomical and functional success rates were then performed. RESULTS: Anatomical success with retinal reattachment was observed in ten of the 17 eyes (58.82%), while functional success measured as difference in the best-corrected visual acuity before and after the surgery were logarithm of the minimum angle of resolution (logMAR) 1.95 ± 0.66 and logMAR 1.51 ± 0.66, respectively (p < 0.05). CONCLUSIONS: This study suggests that, in patients with chronic SRD despite prolonged medical treatment and resolution of inflammation, surgical drainage of subretinal fluid with silicone oil tamponade can achieve anatomical and functional success.

A potential role of crystallin in the vitreous bodies of rats after ischemia-reperfusion injury.

PURPOSE: Ischemia-reperfusion injury (I/R injury) is known not only to induce hypoxic and oxidative stress, but also to cause retinal degeneration in rats. Crystallins, known to inhibit the formation of reactive oxygen species, reduce apoptotic cell death. Our goal was to clarify not only the role of I/R injury-mediated crystallins, but also to evaluate the correlation of these compounds to anti-inflammation in the vitreous body. METHODS: Twenty-four Sprague-Dawley rats were used in this study. We induced I/R injury by clamping the optic nerve for 30 minutes and then releasing it. The vitreous bodies were obtained from the experimental and control subjects 24, 48, and 72 hours after I/R injury. Two-dimensional electrophoresis was performed, and the targeted spots were further investigated using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, spectrophotometry, Western blotting, and histological examination. RESULTS: After I/R injury, 23 spots were identified as crystallins. The ßB2 crystallins were transcriptionally and post-translationally regulated, whereas the αB crystallins were controlled by post-translational modifications in the vitreous bodies of the rats. The total amounts of αA and ß crystallins (including isotypes of ß crystalline) had increased 48 hours after injury. The phosphorylation of αB crystallin (at serine residues 19, 45, and 59) was significantly increased 48 hours later, whereas phosphorylation of ERK1/2 showed the greatest decrease. CONCLUSIONS: During hypoxic and oxidation stress, our results suggest that phosphorylated αB crystalline inhibits RAS, resulting in the inactivation of ERK1/2. The phosphorylation of αB crystallin may be associated with the inflammatory suppression in the vitreous body via the I/R injury model system.

Gene Expression Profile of T-cell Receptors in the Synovium, Peripheral Blood, and Thymus during the Initial Phase of Collagen-induced Arthritis.

BACKGROUND: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. METHODS: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. RESULTS: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3ζ, CD3δ, CD3ε, CD8α, and CD8ß genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. CONCLUSION: This study provides evidence that the genes encoding TCRs including CD3ζ, CD3δ, CD3ε, CD8α, and CD8ß genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.

2',4',6'-Tris(methoxymethoxy) chalcone (TMMC) attenuates the severity of cerulein-induced acute pancreatitis and associated lung injury.

Acute pancreatitis (AP) is an inflammatory disease involving acinar cell injury and rapid production and release of inflammatory cytokines, which play a dominant role in local pancreatic inflammation and systemic complications. 2',4',6'-Tris (methoxymethoxy) chalcone (TMMC), a synthetic chalcone derivative, displays potent anti-inflammatory effects. Therefore, we aimed to investigate whether TMMC might affect the severity of AP and pancreatitis-associated lung injury in mice. We used the cerulein hyperstimulation model of AP. Severity of pancreatitis was determined in cerulein-injected mice by histological analysis and neutrophil sequestration. The pretreatment of mice with TMMC reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (activity of amylase, lipase, trypsin, trypsinogen, and myeloperoxidase and production of proinflammatory cytokines). In addition, TMMC inhibited pancreatic acinar cell death and production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 by inhibiting NF-κB and extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation. Neutralizing antibodies for TNF-α, IL-1ß, and IL-6 inhibited cerulein-induced cell death in isolated pancreatic acinar cells. Moreover, pharmacological blockade of NF-κB/ERK1/2 reduced acinar cell death and production of TNF-α, IL-1ß, and IL-6 in isolated pancreatic acinar cells. In addition, posttreatment of mice with TMMC showed reduced severity of AP and lung injury. Our results suggest that TMMC may reduce the complications associated with pancreatitis.

Relationship between the Glutathione-S-Transferase P1, M1, and T1 Genotypes and Prostate Cancer Risk in Korean Subjects.

PURPOSE: The glutathione-S-transferase (GST)P1, GSTM1, and GSTT1 genotypes have been associated with an increased risk of prostate, bladder, and lung cancers. The aim of this study was to investigate the association between the GSTP1, GSTM1, and GSTT1 genotypes and the risk of prostate cancer in Korean men. MATERIALS AND METHODS: The study group consisted of 166 patients with histologically confirmed prostate cancer. The control group consisted of 327 healthy, cancer-free individuals. The diagnosis of prostate cancer was made by transrectal ultrasound-guided biopsy. Patients with prostatic adenocarcinoma were divided into organ-confined (≤pT2) and non-organ-confined (≥pT3) subgroups. The histological grades were subdivided according to the Gleason score. The GSTP1, GSTM1, and GSTT1 genotypes were determined by using polymerase chain reaction-based methods. The relationship among GSTP1, GSTM1, and GSTT1 polymorphisms and prostate cancer in a case-control study was investigated. RESULTS: The frequency of the GSTM1 null genotype in the prostate cancer group (54.2%) was higher than in the control group (odds ratio=1.53, 95% confidence interval=1.20-1.96). The comparison of the GSTP1, GSTM1, and GSTT1 genotypes and cancer prognostic factors, such as staging and grading, showed no statistical significance. CONCLUSIONS: An increased risk for prostate cancer may be associated with the GSTM1 null genotype in Korean men, but no association was found with the GSTT1 or GSTP1 genotypes.

Significant association between IL-17F promoter region polymorphism and susceptibility to asthma in a Korean population.

BACKGROUND: Individual differences in susceptibility to asthma would be expected because of common DNA variants of single nucleotide polymorphisms (SNPs) across populations. The pro-inflammatory cytokine IL-17F has homology with the IL-17 motif and induces the expression of other inflammatory cytokines in airway epithelial cells. This study aimed to identify IL-17F gene polymorphisms and to determine a possible association between these polymorphisms and susceptibility to asthma through a case-control study in a Korean population. METHODS: We identified SNPs in the IL-17F gene by sequencing. Genotyping was conducted using the high-resolution melting (HRM) method on 424 asthma patients and 548 healthy controls. RESULTS: The genotype and allele frequencies of rs1889570 SNP were significantly different between asthma patients and healthy controls (p = 0.001 and 0.002, respectively). The rs1889570 SNP genotype was also positively associated with the number of peripheral blood eosinophils in asthma patients (p = 0.03). The frequencies of haplotypes AA (p = 0.01), GG (p = 0.01) and AG (p = 0.006) were significantly different between asthma patients and healthy controls. CONCLUSIONS: In this study, we confirmed that the rs1889570 polymorphism of the IL-17F gene is associated with susceptibility to asthma in a Korean population.

p-Glycoprotein ABCB5 and YB-1 expression plays a role in increased heterogeneity of breast cancer cells: correlations with cell fusion and doxorubicin resistance.

BACKGROUND: Cancer cells recurrently develop into acquired resistance to the administered drugs. The iatrogenic mechanisms of induced chemotherapy-resistance remain elusive and the degree of drug resistance did not exclusively correlate with reductions of drug accumulation, suggesting that drug resistance may involve additional mechanisms. Our aim is to define the potential targets, that makes drug-sensitive MCF-7 breast cancer cells turn to drug-resistant, for the anti-cancer drug development against drug resistant breast cancer cells. METHODS: Doxorubicin resistant human breast MCF-7 clones were generated. The doxorubicin-induced cell fusion events were examined. Heterokaryons were identified and sorted by FACS. In the development of doxorubicin resistance, cell-fusion associated genes, from the previous results of microarray, were verified using dot blot array and quantitative RT-PCR. The doxorubicin-induced expression patterns of pro-survival and pro-apoptotic genes were validated. RESULTS: YB-1 and ABCB5 were up regulated in the doxorubicin treated MCF-7 cells that resulted in certain degree of genomic instability that accompanied by the drug resistance phenotype. Cell fusion increased diversity within the cell population and doxorubicin resistant MCF-7 cells emerged probably through clonal selection. Most of the drug resistant hybrid cells were anchorage independent. But some of the anchorage dependent MCF-7 cells exhibited several unique morphological appearances suggesting minor population of the fused cells maybe de-differentiated and have progenitor cell like characteristics. CONCLUSION: Our work provides valuable insight into the drug induced cell fusion event and outcome, and suggests YB-1, GST, ABCB5 and ERK3 could be potential targets for the anti-cancer drug development against drug resistant breast cancer cells. Especially, the ERK-3 serine/threonine kinase is specifically up-regulated in the resistant cells and known to be susceptible to synthetic antagonists.

A case of optic neuritis complicating herpes zoster ophthalmicus in a child.

Here we report a case of optic neuritis in the setting of herpes zoster ophthalmicus (HZO) in a child. A six-year-old girl presented with HZO in the right eye. During the hospitalization, her visual acuity decreased. Fluorescein angiography (FAG) and optical coherence tomography revealed optic neuritis in the affected eye. Visual acuity improved with one month of treatment with acyclovir and steroids. FAG analysis showed no evidence of leakage at the optic disc. At one year post treatment, the patient's fundus exam and vision were normal. Therapy with antivirals and steroids may be effective in patients with childhood HZO optic neuritis.

The assessment of bee venom responses in an experimental model of mono-arthritis using Tc-99m DPD bone scintigraphy.

OBJECTIVES: Several recent studies have shown that bee venom (BV) has an anti-nociceptive and anti-inflammatory effect on arthritis. However, objective methods for evaluation of the therapeutic effect of BV is insufficient in animal studies and clinical trials. Our purpose was to determine the usefulness of bone scintigraphy using Tc-99m DPD (3,3-diphosphono-1,2-propan-dicarbonacid) about effects of BV applied to carrageenan-induced mono-arthritis (CIA) model. METHODS: Mono-arthritis was induced by an intra-articular injection of carrageenan in Sprague-Dawley rats. Administration of BV (0.8 mg/kg) was performed at 30 min before and at 4 h after the induction of mono-arthritis. We assigned rats to BV-before, BV-after, control-before and control-after groups and compared the results of each group by the weight-loading test and bone scintigraphy. The rats received an intravenous injection of 37 MBq of Tc-99m DPD by the tail vein and then scanning was performed at 4 and 24 h after the injection. Visual assessment and quantitative analysis were performed for both knees. RESULTS: The BV-before and BV-after groups were more improved than the control groups on the weight load test (p < 0.05). Bone scintigraphy showed lower activity in the BV-before group than in the control-before group (p < 0.05) on the 4 h imaging. However, a significant difference in the BV-before and BV-after groups was not observed on the 24 h imaging. CONCLUSIONS: BV had therapeutic effects by anti-nociceptive and anti-inflammatory activity in the CIA and bone scintigraphy performed on 4 h imaging provided visual and quantitative information for the assessment of the therapeutic response to BV as an objective method in mono-arthritis model.

Identification of single nucleotide polymorphisms in the TNFRSF17 gene and their association with gastrointestinal disorders.

TNFRSF17 is preferentially expressed in mature B lymphocytes, and may be important for the development of B cells. TNFRSF17 is selected as a candidate susceptibility gene to IBD pathogenesis by our cDNA microarray analysis, and we showed the specific expression of TNFRSF17 in resting and activated CD19(+) cells obtained from human blood. We identified four SNPs (g-1729G>A, g.2295T>C, g.2445G>A and g.2493G>A) and one variation site (g.894delT) in the TNFRSF17 gene using direct sequencing analysis. In addition, the association of the genotype and allelic frequencies of these SNPs was studied in healthy controls and in patients with ulcerative colitis (UC) or irritable bowel syndrome (IBS). Although, the genotype and allelic frequencies of these SNPs, in the UC and IBS patients, were not significantly different from those in the healthy controls, the distribution of the AAG, GGA, AGG and AAA haplotypes, of the SNPs (g.-1729G>A, g.2445G> A and g.2493G>A) associated with the TNFRSF17 gene, in the UC patients, were notably different from those of the healthy controls (P = 0.002, 0.002, 4.7E-4 and 3.3E-6, respectively). Moreover, the frequencies of the AAG, AGG, GAG and GAA haplotypes were significantly different in the IBS patients compared to the healthy controls (P = 4.2E-5, 4.4E-17, 1.8E-22 and 1.6E-10, respectively). These results suggest that the haplotypes of the TNFRSF17 polymorphisms might be associated with UC and IBS susceptibility.

Vitamin D receptor gene Alw I, Fok I, Apa I, and Taq I polymorphisms in patients with urinary stone.

OBJECTIVES: To evaluate vitamin D receptor (VDR) gene polymorphisms in Korean patients so as to identify the candidate genes associated with urinary stones. Urinary stones are a multifactorial disease that includes various genetic factors. METHODS: A normal control group of 535 healthy subjects and 278 patients with urinary stones was evaluated. Of 125 patients who presented stone samples, 102 had calcium stones on chemical analysis. The VDR gene Alw I, Fok I, Apa I, and Taq I polymorphisms were evaluated using the polymerase chain reaction-restriction fragment length polymorphism analysis. Allelic and genotypic frequencies were calculated to identify associations in both groups. The haplotype frequencies of the VDR gene polymorphisms for multiple loci were also determined. RESULTS: For the VDR gene Alw I, Fok I, Apa I, and Taq I polymorphisms, there was no statistically significant difference between the patients with urinary stones and the healthy controls. There was also no statistically significant difference between the patients with calcium stones and the healthy controls. A novel haplotype (Ht 4; CTTT) was identified in 13.5% of the patients with urinary stones and in 8.3% of the controls (P = .001). The haplotype frequencies were significantly different between the patients with calcium stones and the controls (P = .004). CONCLUSIONS: The VDR gene Alw I, Fok I, Apa I, and Taq I polymorphisms does not seem to be candidate genetic markers for urinary stones in Korean patients. However, 1 novel haplotype of the VDR gene polymorphisms for multiple loci might be a candidate genetic marker.

Results of extensive surgical treatment of seven consecutive cases of postoperative fungal endophthalmitis.

PURPOSE: Postoperative endophthalmitis is a dreaded outcome of any intraocular surgery. Fungal endophthalmitis is a particularly severe complication that poses a significant threat of blindness. We experienced seven consecutive cases of postoperative fungal endophthalmitis stemming from a single local clinic in which extensive early intervention resulted in favorable final visual acuity. METHODS: The present study is retrospective observational case series of fungal endophthalmitis. The initial case, as diagnosed by fungal culture, resulted in blindness. In the ensuing eight months, seven consecutive cases were referred to our institution. All were presumed to be fungal endophthalmitis as the cases possessed similar inflammatory findings to the preceding case and occurred in the same environment. Extensive surgical and antifungal treatment was immediately administered, including complete vitrectomy with removal of the intraocular lens and lens capsule and Amphotericin B injections. RESULTS: Retinal infiltration was identified in three cases and the lesion site was photocoagulated with an endolaser. All cases were confirmed fungal endophthalmitis by culture (4 cases: Candida parapsilosis, one case each: Fusarium, Acremonium, Candida tropicalis) and five cases required secondary intraocular lens implantation. Final corrected visual acuity ranged from 20/20 to 40/200 by the Snellen chart. CONCLUSIONS: Early extensive surgical intervention and antifungal agent administration may result in favorable visual outcomes in patients with fungal endophthalmitis following cataract surgery.

Effects of heme oxygenase-1 inducer and inhibitor on experimental autoimmune uveoretinitis.

PURPOSE: Experimental autoimmune uveoretinitis (EAU) is an animal model of posterior uveitis and heme oxygenase-1 (HO-1) is a well-known anti-oxidant factor. However, there is no report a protective role of HO-1 on EAU in vivo. To verify that HO-1 is induced in EAU by interphotoreceptor retinoid-binding protein (IRBP), that an HO-1 inducers ameliorates the associated inflammation, and that an HO-1 inhibitor exacerbates this inflammation. METHODS: Forty four Lewis rats were given either 40 mol/kg hemin or 40 mol/kg SnPP (tin protoporphyrin IX) by intraperitoneal injection and twenty two uveitis control rats were injected with 0.5 mL of saline once daily 5-20 days after IRBP immunization inducing EAU. Three normal control rats were used for Western blotting and ELISA assay of HO-1. The clinical uveitis signs of inflammation were scored in the three groups from 0 to 4 on alternate three days. To confirm the clinical results, histological and immunohistochemical stain of HO-1 were performed on the day of peak inflammation and Western blotting and ELISA assay of HO-1 were performed on 6th, 12th and 18th day after IRBP immunization. RESULTS: Hemin, an inducer of HO-1, ameliorated the clinical signs of EAU. In contrast, SnPP-treated rats show that the severity of the clinical sign were exacerbated at the peak period of the disease. These results are roughly compatible with histological, immunoblotting, and immunohistochemical evaluations and an ELISA assay of HO-1. CONCLUSIONS: We suggest that HO-1 plays an important protective role in EAU.

Post-translational modification of crystallins in vitreous body from experimental autoimmune uveitis of rats.

Experimental autoimmune uveitis (EAU) is a well-known animal model of posterior uveitis that is one of the major causes of blindness. EAU could be induced in susceptible animals (i.e., Lewis rat) by immune reactions using evolutionarily conserved retinal proteins, such as interphoto-receptor retinoid binding protein (IRBP), or epitaphs of the protein. First, we prepared the following four test groups that subsequently increased or decreased inflammation. (1) Normal control group, (2) IRBP-induced uveitis group, (3) Hemin-treated uveitis group, and (4) Sn(IV) protoporphyrin IX dichloride (SnPP)-treated uveitis group. Second, in the vitreous bodies of Lewis rats, the infiltrated proteins were analyzed using two-dimensional electrophoresis (2-DE), MALDI-TOF/MS, and Micro LC/LC-MS/MS analysis. Finally, Western blotting was applied to confirm the relative amount of crystallins and phosphorylation sites of alphaB-crystallin. Thirty spots were identified in vitreous bodies, and 27 of these spots were members of the crystallin family. Unlike betaA4- and B2-crystallins (that were significantly increased without truncation), alphaA- and B-crystallins were only truncated in EAU vitreous body. Taken as a whole, in the rat EAU model, we suggest that post-translational truncations of alphaA- and alphaB-crystallins, phosphorylation of alphaB-crystallin, and new production of betaA4- and betaB2-crystallins are intercorrelated with uveitis progression and inflammatory responses.

Identification of polymorphisms in human interleukin-27 and their association with asthma in a Korean population.

Interleukin 27 (IL-27) acts as a versatile cytokine in the early regulation of Th1 initiation and in the negative regulation of the Th2 factor GATA-3. IL-27, which was discovered as a novel heterodimeric cytokine of the IL-12 family, consists of two subunits, the Epstein-Barr virus-induced gene 3 (EBI3) and p28. The IL-27 cytokine is mediated by one of the receptor chains (WSX-1) of the IL-27 receptor that is highly expressed on CD4(+) T lymphocytes and NK cells. Although signaling of IL-27/WSX-1 interactions have been recognized in the down-regulation of airway hyper-reactivity and in lung inflammation during the development of allergic asthma, little is known about the role of single nucleotide polymorphisms (SNPs) of IL-27 and individual susceptibility to asthma. To address this question, we have examined the five exons and the boundary intron sequences of IL-27P28, including the promoter regions, with the aim of identifying sites of variation that may be useful for understanding the genetic influences of this gene. We identified four SNPs, g.-964A > G, g.2905T > G, g.4603G > A and g.4730T > C, and analyzed the genotype and allele frequencies between asthma patients and healthy controls. Our results strongly suggest that the g.-964A > G polymorphism of IL-27p28 is most likely associated with susceptibility to asthma. Moreover, we elucidate the haplotype frequencies of g.2905T > G, g.4603G > A and g.4730T > C in terms of their relative correlation with asthma patients and healthy controls.