Je Moon Woo

Elevated plasma pentraxin 3 levels are associated with development and progression of diabetic retinopathy in Korean patients with type 2 diabetes mellitus.

PURPOSE To evaluate the association between elevated levels of plasma pentraxin 3 (PTX3) and the development and/or progression of diabetic retinopathy (DR). METHODS In this case-control study, 92 diabetic patients with DR (group 3), 30 diabetic patients without DR (group 2), and 41 normal subjects (group 1) were enrolled. Log-transformed values of plasma PTX3 and high-sensitivity C-reactive protein (hsCRP) concentrations were measured and used in our analysis. For subgroup analysis, group 3 was divided into four subgroups: mild, moderate, severe nonproliferative, and proliferative DR. RESULTS In our 163 participants, average plasma PTX3 levels were 916.1 ± 532.2, 1093.7 ± 1034.2, and 1817.9 ± 1776.9 pg/mL for groups 1, 2, and 3, respectively. The duration of diabetic mellitus (DM), glycated hemoglobin (HbA1c), log hsCRP, and log PTX3 were significantly different between the three groups (P = 0.008, P < 0.001, P = 0.046, and P < 0.001, respectively). In subgroup analysis, plasma log PTX3 levels increased in correlation with the severity of DR (R = 0.372, P < 0.001). Multivariate logistic analysis showed that the correlation between DR development and duration of DM and log PTX3 values was significant (P = 0.014 and P = 0.025, respectively), whereas correlation with log hsCRP values was not significant in univariate analysis (P = 0.129). The receiver operating characteristic curves of DR development were plotted using log PTX3 and log hsCRP values, and the area under the curves was found to be 0.721 (P = 0.001) and 0.614 (P = 0.087), respectively. CONCLUSIONS Plasma PTX3 is positively associated with DR development and progression, and may be a more accurate predictor of DR development than hsCRP.

Therapeutic Effect of Topical Adiponectin in a Mouse Model of Desiccating Stress–Induced Dry Eye

PURPOSE To investigate the therapeutic effect of topical adiponectin in a mouse model of experimental dry eye (EDE). METHODS EDE was created by desiccating stress in 6- to 8-week old female C57BL/6 mice. Eye drops consisting of 0.0001%, 0.001%, or 0.01% adiponectin, or balanced salt solution (BSS), were applied in EDE. Tear volume and corneal irregularity score were measured at 5 and 10 days after treatment. Levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and monokine induced by interferon-γ (MIG) were measured in the conjunctiva and lacrimal gland using a multiplex immunobead assay at 10 days. Periodic acid-Schiff staining, immunohistochemistry, and flow cytometry were also performed. RESULTS Mice treated with 0.001% or 0.01% adiponectin showed a significant improvement in tear volume and corneal irregularity compared with the EDE control and BSS-treated groups. A significant decrease in the levels of IL-1β, IL-6, TNF-α, IFN-γ, and MIG and staining intensity of TNF-α was observed in the 0.001% and 0.01% adiponectin-treated groups, compared with the other groups, in the conjunctiva and lacrimal gland. In the 0.001% and 0.01% adiponectin-treated groups, the density of conjunctival goblet cells was higher and the number of CD4+CXCR3+ T cells was lower than in the other groups. However, there were no significant differences in all parameters between the 0.0001% adiponectin and control groups. CONCLUSIONS Topical application of adiponectin can markedly improve clinical signs and decrease inflammation in the ocular surface and lacrimal gland of EDE, suggesting that adiponectin eye drops may be used as a therapeutic agent for dry eye disease.

Effects of Diabetic Macular Edema on Repeatability of Retinal Nerve Fiber Layer Thickness Measurements at the Macular and Peripapillary Area Using Swept-Source Optical Coherence Tomography.

ABSTRACT Purpose: To investigate the repeatability of macular and peripapillary retinal nerve fiber layer (RNFL) thickness measurements made using swept-source optical coherence tomography (SS-OCT) and automated segmentation. Measurements were made in non-diabetic controls and in patients with diabetic retinopathy (DR) with or without diabetic macular edema (DME). Materials and Methods: A total of 131 eyes of 131 participants were included. Fifty-one eyes with DR had no DME (DME[–]), 45 eyes with DR had DME (DME[+]), and 35 eyes were healthy. Measurements of RNFL and full retinal thickness were simultaneously obtained with SS-OCT in the peripapillary area and in the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields using the wide three-dimensional mode. All measurements were made twice on the same day by a single examiner to test intra-observer repeatability. Intraclass correlation coefficients (ICCs) and coefficients of repeatability were examined to evaluate repeatability. Results: Average macular and temporal peripapillary RNFL thickness values were greater in the DME[+] group (36.4 ± 13.2 and 83.8 ± 19.4 µm, respectively) than in the control (27.4 ± 3.5 and 73.5 ± 11.4 µm, respectively) and DME[–] (27.9 ± 3.4 µm and 70.3 ± 11.3 µm, respectively) groups (both P < 0.001). The ICCs of average macular (control: 0.982, DME[–]: 0.913, and DME[+]: 0.970) and peripapillary (control: 0.972, DME[–]: 0.973, and DME[+]: 0.958) RNFL thickness measurements indicated good repeatability in all three study groups. Conclusions: Although the ICCs of average RNFL thickness measurements were relatively lower in eyes with DR than in healthy controls, the intra-observer repeatability of SS-OCT RNFL and full retinal thickness measurements is sufficiently reliable for them to be clinically useful.

Elevated Plasma Pentraxin 3 and Its Association with Retinal Vein Occlusion

Purpose To evaluate plasma pentraxin 3 (PTX3) in patients with retinal vein occlusion (RVO), and investigate the possibility of its role as a predictive biomarker. Methods Nested case-control study. The study included 57 patients with RVO and 45 age- and gender-matched subjects without RVO as controls. Plasma PTX3 and C-reactive protein concentration were measured in both groups a posteriori from frozen samples by using an enzyme-linked immunosorbent assay kit. Results The measured PTX3 value for the RVO group was 1,508 ± 1,183 pg/mL (mean ± standard deviation) and 833 ± 422 pg/mL for the controls (p < 0.001). There was no significant difference in PTX3 levels between patients with central retinal vein occlusion and branched retinal vein occlusion (1,468 ± 1,300 vs. 1,533 ± 1,121 pg/mL; p = 0.818). Conclusions Our data seems to support the role of chronic inflammation and ischemia in the development of RVO. It is possible that PTX3 can be used as a diagnostic biomarker of RVO.

Tunicamycin-induced Endoplasmic Reticulum Stress Upregulates the Expression of Pentraxin 3 in Human Retinal Pigment Epithelial Cells

Purpose To investigate the production of long pentraxin 3 (PTX3) in response to tunicamycin-induced endoplasmic reticulum (ER) stress and its role in ER stress-associated cell death, PTX3 expression was evaluated in the human retinal pigment epithelial cell line, ARPE-19. Methods PTX3 production in ARPE-19 cells was analyzed in the absence or presence of tunicamycin treatment by enzyme-linked immunosorbent assay. PTX3 protein and mRNA levels were estimated using western blot analysis and real-time reverse transcription-polymerase chain reaction, respectively. Protein and mRNA levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and ARPE-19 cell viability were measured in the presence of tunicamycin-induced ER stress in control or PTX3 small hairpin RNA (shRNA)-transfected ARPE-19 cells. Results The protein and mRNA levels of PTX3 were found to be significantly increased by tunicamycin treatment. PTX3 production was significantly decreased in inositol-requiring enzyme 1α shRNA-transfected ARPE-19 cells compared to control shRNA-transfected cells. Furthermore, pretreatment with the NF-κB inhibitor abolished tunicamycin-induced PTX3 production. Decreased cell viability and prolonged protein and mRNA expression of CHOP were observed under tunicamycin-induced ER stress in PTX3 shRNA transfected ARPE-19 cells. Conclusions These results suggest that PTX3 production increased in the presence of tunicamycin-induced ER stress. Therefore, PTX3 could be an important protector of ER stress-induced cell death in human retinal pigment epithelial cells. Inositol-requiring enzyme 1α and the NF-κB signaling pathway may serve as potential targets for regulation of PTX3 expression in the retina. Therefore, their role in PTX3 expression needs to be further investigated.

Foveal Avascular Zone Area Changes Analyzed Using OCT Angiography after Successful Rhegmatogenous Retinal Detachment Repair

ABSTRACT Purpose: To investigate foveal avascular zone (FAZ) area after surgery in patients with rhegmatogenous retinal detachment (RRD) that involved or uninvolved the macula, and to evaluate the correlation between FAZ area and visual outcomes using swept-source optical coherence tomography angiography (OCTA). Materials and Methods: This retrospective case–control study included 34 eyes (34 patients) with recent onset RRD that were successfully repaired with a single, uncomplicated surgical procedure (pars plana vitrectomy with gas tamponade). The changes of FAZ area were examined by OCTA after surgery. The unaffected fellow eye was used as a control for additional comparison. Results: Both superficial and deep FAZ area were significantly larger in the macula-off group (superficial: 0.374 ± 0.112, deep: 0.702 ± 0.193 mm2) than in the macula-on group (superficial: 0.282 ± 0.105, deep: 0.543 ± 0.114 mm2) following surgery. The deep FAZ area was also markedly larger in the macula-off group than in the control group (0.532 ± 0.124 mm2). Correlation analyses revealed that both superficial (ρ = 0.555, P = 0.015) and deep FAZ (ρ = 0.616, P = 0.005) areas were negatively correlated with postoperative best-corrected visual acuity in the macula-off RRD group. Conclusions: The FAZ area enlargement after successful surgical repair in macula-off RRD eyes may indicate that there is an ischemic damage to retinal capillary plexus in fovea.

The Wound Healing Effects of Adiponectin Eye Drops after Corneal Alkali Burn

ABSTRACT Purpose: To investigate the wound healing effect of adiponectin eye drops following corneal alkali burn. Materials and Methods: A chemical burn was induced using 0.1 M NaOH in both adenovirus 12-SV40 hybrid-transformed human corneal epithelial (HCE-2) cells and C57BL/6 mice. The injured HCE-2 and mice were then treated using either 0.1% hyaluronic acid (HA) or adiponectin at 0.0001%, 0.001%, or 0.01% concentration. The viability of the HCE-2 cells was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The wound healing rate of the HCE-2 cells was evaluated using a migration assay 4, 8, 12, 24, and 48 h after chemical injury. In mice, corneal epithelial defects and degree of haze were analyzed 6 h and 1, 2, 3, 6, and 7 days after chemical injury. Seven days after injury, the concentrations of IL-1β and transforming growth factor-β (TGF-β) in the cornea were measured using enzyme-linked immunosorbent assay, and histological analysis was also performed. Results: The viability of HCE-2 cells was not affected by adiponectin at any of the concentrations used. In HCE-2 cells treated using either 0.001% or 0.01% adiponectin, the wound healing rate after 4 h was significantly faster than in the control and HA-treated groups. With regard to mice, the 0.001% and 0.01% adiponectin-treated groups showed a significant improvement in epithelial defect parameters and haze scores at 3, 5, and 7 days after chemical injury. A significant decrease in IL-1β and TGF-β levels was observed in the 0.001% and 0.01% adiponectin-treated groups compared to the other groups. Histologically, corneal thickness and the inflammatory cells were also decreased in the adiponectin-treated groups. Conclusions: Topical adiponectin (both 0.001% and 0.01%) increased epithelial migration and improved clinical signs and inflammation on the ocular surface after alkali burn, suggesting that adiponectin can promote wound healing in the cornea.