Increasing evidence supports an association between age-related loss of muscle mass and insulin resistance. However, the association has not been fully investigated in the general population. Thus, we investigated the association between appendicular skeletal muscle mass (ASM) and insulin resistance in an elderly Korean population. This cross-sectional study included 158 men (mean age, 71.8) and 241 women (mean age, 70.6) from the Korean Social Life, Health and Aging Project, which started in 2011. In this study, ASM was measured by bioelectrical impedance analysis and was analyzed in three forms: ASM (kg), ASM/height(2) (kg/m(2)), and ASM/weight (%). The homeostasis model assessment of insulin resistance (HOMA-IR) was used as a measure of insulin resistance. The relationships between the ASM values and the HOMA-IR were investigated by multiple linear regression models. The HOMA-IR was positively associated with ASM (β=0.43, P<0.0001) and ASM/height(2) (β=0.36, P<0.0001) when adjusted for sex and age. However, after additional adjustment for body weight, HOMA-IR was inversely associated with ASM (β=-0.43, P<0.001) and ASM/height(2) (β=-0.30, P=0.001). Adjustment for other potential confounders did not change these associations. Conversely, HOMA-IR was consistently and inversely associated with ASM/weight before and after adjustment for other potential confounders. Our results support the idea that lower skeletal muscle mass is independently associated with insulin resistance in older adults. When evaluating sarcopenia or muscle-related conditions in older adults, their whole body sizes also need to be considered.

Purpose. To introduce a tonicity response gene regulator, NFAT (nuclear factor of activated T-cell)-5 and determine its expression mechanism and specific roles in human limbal epithelial cell (HLECs) subjected to hyperosmolar stress. methods. NFAT5 expression was determined in various hyperosmolar conditions in HLECs by RT-PCR and Western immunoblot analyses. NFAT5 translocation during hyperosmolar stress was observed by immunocytochemistry. NFAT5-related signal transduction activity was measured on the basis of inhibition of NF-κB (nuclear factor-κB), and MAPK activity. TNF-α and IL-1β, -6, and -8 levels were determined after inhibition of NFAT5 and/or NF-κB. Hyperosmotic apoptotic cell death, with or without inhibition of NFAT5, was measured by flow cytometry. results. NFAT5 was induced and translocated to the nucleus under conditions of hyperosmolar stress. It was inhibited by SB239063, a p38 MAPK inhibitor. Among the inflammatory cytokines induced in hyperosmolar stress conditions, IL-1β and TNF-α levels were significantly reduced after inhibition of NFAT5. Of interest, even after 48 hours of hyperosmolar stress, 45% of HLECs survived. HLEC apoptosis increased markedly as a result of NFAT5 suppression. Moreover, most of the HLECs underwent cell death on dual inhibition of NF-κB and NFAT5. conclusions. NFAT5 is induced and translocates to the nucleus in HLECs undergoing hyperosmolar stress through activation of p38. IL-1 β and TNF-α are induced via NFAT5 activation. Our data collectively indicate that NFAT5 may be an important gene regulator and survival factor in hyperosmolar stressed HLECs.

Purpose.: The purpose of this study was to investigate the effectiveness of tumor necrosis factor (TNF)-α blocker for treatment of dry eye (DE)-induced inflammation and determine a more effective method to suppress lacrimal gland inflammation. Efficacy of topical versus systemic administration of TNF-α blockers was determined using a murine dry eye (DE) model. Methods.: The TNF-α blocker HL036 was developed by modification of the TNF receptor I. Protein purity, binding affinity, and clearance of TNF-α was compared with etanercept. Using DE-induced C57BL/6 mice, corneal erosion and goblet cell counts were measured after subcutaneous or topical treatment with etanercept or HL036. Inflammatory cytokines in cornea and lacrimal glands were determined by quantitative RT-PCR and ELISA. Results.: HL036 showed TNF-α binding affinity comparable to etanercept, as measured by surface plasmon resonance. HL036 concentration was significantly higher in cornea and anterior segment than etanercept and effectively eliminated TNF-α on ocular surfaces. Etanercept was preferentially concentrated in the posterior segment. Corneal erosion and goblet cell counts were improved only with topically applied etanercept and HL036. Ocular surface IFN-γ, IL-6, and IL-21 were significantly decreased by topical HL036. DE-induced lacrimal gland IFN-γ and IL-6 expression was effectively suppressed by topical etanercept and HL036. Conclusions.: Topical TNF-α blockers effectively suppressed lacrimal gland and corneal inflammation by suppressing IFN-γ, IL-21, and IL-6. Differences in TNF-α affinity, clearance, and local concentration of blockers may account for the anti-inflammatory effects in different ocular regions.

Although early glaucoma detection is important to prevent visual loss due to disease progression, its clinical diagnosis in highly myopic eyes is still difficult. Many studies using optical coherence tomography (OCT) angiography (OCTA) reported decreased vessel density (VD) in glaucomatous eyes compared to normal eyes. We evaluated the diagnostic ability of peripapillary VD and macular VD measured by OCTA, comparing them with conventional valuables such as peripapillary retinal nerve fibre layer (RNFL) thickness and macular ganglion cell-inner plexiform layer (GCIPL) thickness measured by OCT. We also calculated the average VD ratio (VDR) (average outer macular VD/average inner macular VD), superior VDR (superior outer macular VD/average inner macular VD), and inferior VDR (inferior outer macular VD/average inner macular VD). Totally, 169 eyes from 169 subjects were enrolled. Among OCTA measurements, the best diagnostic parameters were average VDR (AUROC: 0.852 and 0.909) and inferior VDR (AUROC: 0.820 and 0.941) in nonhighly and highly myopic eyes, respectively. Inferior VDR showed better diagnostic ability than most of the other OCT measurements including peripapillary RNFL thickness and macular GCIPL thickness in highly myopic eyes. Accordingly, OCTA measurements can be useful for diagnosing glaucoma in highly myopic eyes, especially when using calculated indices such as average VDR or inferior VDR.

Purpose.: We aimed to determine the role of CCR7⁺CD11b⁺ cell lymph node (LN) homing and T-cell differentiation in dry eye (DE)-induced immunopathogenesis and investigate the therapeutic effects of cyclooxygenase-2 (COX-2) and prostaglandin E₂/eicosanoid-prostanoid (PGE₂/EP) inhibitors against DE. Methods.: Six-week-old female C57BL/6 mice were housed in a controlled-environment chamber and administered topical selective COX-2 inhibitors or EP2 antagonists. Expression of major histocompatibility complex (MHC)-II^high, CD11b⁺, CCR7⁺, IFN-γ⁺, IL-17⁺, and CD4⁺ in the corneas and draining LNs was evaluated using flow cytometry. Mixed lymphocyte reactions (MLRs) with carboxyfluorescein diacetate succinimidyl ester labeling and intracellular cytokine staining were used to verify DE-induced corneal dendritic cell function. mRNA expression of COX-2, EPs, and proinflammatory cytokines in ocular surface was evaluated using quantitative RT-PCR and immunohistochemical staining. Results.: Dry eye significantly increased MHC-II^highCD11b⁺ and CCR7⁺CD11b⁺ cells in the cornea and LNs, and MLR revealed CCR7⁺CD11b⁺ cells from DE corneas stimulated IL-17⁺CD4⁺ cell proliferation. mRNA levels of COX-2, EP2, IFN-γ, TNF-α, IL-6, and IL-17 were significantly higher in DE ocular surface but were suppressed by topical COX-2 inhibitors and EP2-specific blockers. Immunohistochemical staining showed COX-2 and matrix metalloproteinase expression in DE corneal epithelia that was diminished by both topical treatments. Furthermore, both topical treatments significantly reduced frequencies of MHC-II^high, CD11b⁺, and CCR7⁺CD11b⁺ cells in the corneas and LNs, but also IL-17⁺CD4⁺ cells in LNs. Conclusions.: Topical COX-2/EP2 treatment reduces CCR7⁺CD11b⁺ cells on the ocular surface with inhibition of cellular LN homing and suppresses Th17 immune response, suggesting the COX-2/PGE₂/EP axis contributes to immuno-inflammatory pathogenesis on the ocular surface and may be a novel therapeutic target in DE.

Background/Aims To analyse intraocular pressure (IOP) changes over a period of 1 year after intravitreal dexamethasone (DEX, Ozurdex) implant injection and to compare the results with those of previously published studies that involved non-Asian populations. Methods A retrospective observational study was conducted. A total of 540 eyes of 503 patients who received DEX implant injection and were diagnosed with macular oedema (ME) due to various retinal diseases were examined. IOP was measured prior to injection and at 1 week, 1 month, 2 months, 3 months, 6 months and 12 months after DEX implant injection. IOP elevation was divided into four categories: postinjection IOP of >35 mm Hg, >30 mm Hg and >25 mm Hg, and an IOP elevation of >10 mm Hg, relative to the baseline measurement. Results The mean baseline IOP was 13.45±2.95. The mean IOP gradually increased until 2 months postinjection (IOP=16.85±5.96 mm Hg, p25 mm Hg in 57 eyes (10.6%), >30mm Hg in 29 eyes (5.4%) and >35mm Hg in 9 eyes (1.7%); IOP exhibited >10 mm Hg elevation from the baseline IOP in 61 eyes (11.3%). Overall, the incidence rate of IOP elevation after DEX treatment was 12.6% (68 eyes). Among the 68 eyes (12.6%) with elevated IOP, 60 (11.1%) required treatment: 59 (10.9%) required IOP-lowering medication and 1 (0.2%) ultimately required surgical interventions. Conclusions The incidence of adverse IOP elevation requiring the prolonged use of IOP-lowering medication and surgical intervention after DEX implantation was significantly lower than the incidence reported in previous Western population-based studies. Intravitreal DEX injection may therefore be an effective and relatively safe treatment modality for ME in Asian patients.