Martha Kim

The Effect of Silica Nanoparticles on Human Corneal Epithelial Cells.

Ocular drug delivery is an interesting field in current research. Silica nanoparticles (SiNPs) are promising drug carriers for ophthalmic drug delivery. However, little is known about the toxicity of SiNPs on ocular surface cells such as human corneal epithelial cells (HCECs). In this study, we evaluated the cytotoxicity induced by 50, 100 and 150 nm sizes of SiNPs on cultured HCECs for up to 48 hours. SiNPs were up-taken by HCECs inside cytoplasmic vacuoles. Cellular reactive oxygen species generation was mildly elevated, dose dependently, with SiNPs, but no significant decrease of cellular viability was observed up to concentrations of 100 μg/ml for three different sized SiNPs. Western blot assays revealed that both cellular autophagy and mammalian target of rapamycin (mTOR) pathways were activated with the addition of SiNPs. Our findings suggested that 50, 100 and 150 nm sized SiNPs did not induce significant cytotoxicity in cultured HCECs.

Cross-Modal and Intra-Modal Characteristics of Visual Function and Speech Perception Performance in Postlingually Deafened, Cochlear Implant Users

Evidence of visual-auditory cross-modal plasticity in deaf individuals has been widely reported. Superior visual abilities of deaf individuals have been shown to result in enhanced reactivity to visual events and/or enhanced peripheral spatial attention. The goal of this study was to investigate the association between visual-auditory cross-modal plasticity and speech perception in post-lingually deafened, adult cochlear implant (CI) users. Post-lingually deafened adults with CIs (N = 14) and a group of normal hearing, adult controls (N = 12) participated in this study. The CI participants were divided into a good performer group (good CI, N = 7) and a poor performer group (poor CI, N = 7) based on word recognition scores. Visual evoked potentials (VEP) were recorded from the temporal and occipital cortex to assess reactivity. Visual field (VF) testing was used to assess spatial attention and Goldmann perimetry measures were analyzed to identify differences across groups in the VF. The association of the amplitude of the P1 VEP response over the right temporal or occipital cortex among three groups (control, good CI, poor CI) was analyzed. In addition, the association between VF by different stimuli and word perception score was evaluated. The P1 VEP amplitude recorded from the right temporal cortex was larger in the group of poorly performing CI users than the group of good performers. The P1 amplitude recorded from electrodes near the occipital cortex was smaller for the poor performing group. P1 VEP amplitude in right temporal lobe was negatively correlated with speech perception outcomes for the CI participants (r = -0.736, P = 0.003). However, P1 VEP amplitude measures recorded from near the occipital cortex had a positive correlation with speech perception outcome in the CI participants (r = 0.775, P = 0.001). In VF analysis, CI users showed narrowed central VF (VF to low intensity stimuli). However, their far peripheral VF (VF to high intensity stimuli) was not different from the controls. In addition, the extent of their central VF was positively correlated with speech perception outcome (r = 0.669, P = 0.009). Persistent visual activation in right temporal cortex even after CI causes negative effect on outcome in post-lingual deaf adults. We interpret these results to suggest that insufficient intra-modal (visual) compensation by the occipital cortex may cause negative effects on outcome. Based on our results, it appears that a narrowed central VF could help identify CI users with poor outcomes with their device.

Systemic Comorbidities of Dry Eye Syndrome: The Korean National Health and Nutrition Examination Survey V, 2010 to 2012.

Purpose: To identify systemic comorbidities in patients with dry eye syndrome in South Korea. Methods: From 2010 to 2012, 17,364 participants aged 20 or older were randomly included in the nationwide Korean National Health and Nutrition Examination Survey V. The prevalence of dry eye syndrome and demographics of these patients were investigated. We performed conditional logistic regression analyses based on age, sex, residential area, education level, occupation type, and household income level to obtain the odds ratio for each systemic comorbidity among subjects with and without dry eye syndrome. Results: The prevalence of dry eye syndrome in this study was 10.4%. Age [adjusted odds ratio (AOR): 1.02], female gender (AOR: 3.01), and indoor occupation (AOR: 1.30) were associated with a higher prevalence of dry eye syndrome and found to be less prevalent in those residing in rural areas (AOR: 0.73) and with lower education levels (AOR: 0.66–0.99). With regard to systemic comorbidities, dyslipidemia (AOR: 1.63), degenerative arthritis (AOR: 1.56), rheumatoid arthritis (AOR: 1.44), thyroid disease (AOR: 1.79), and renal failure (AOR: 2.56) were associated with a significantly higher prevalence of dry eye syndrome. Conclusions: We found that patients with dry eye syndrome have a higher prevalence of several systemic comorbidities. A more comprehensive therapeutic approach considering the effect of systemic medication may be necessary in these patients.

Defect band behavior in p‐Cd0.96Zn0.04Te by hydrogen passivation

Photoluminescence measurements were carried out in order to investigate the dependence of the optical properties of p‐Cd0.96Zn0.04Te single crystals on hydrogen passivation conditions. After the p‐Cd0.96Zn0.04Te was annealed at 500 °C in a Cd atmosphere for 5 h, the luminescence due to the recombination of the electrons in the conduction band with acceptors (eA°) and to the donor–acceptor pair (DAP) transitions disappeared. After the p‐Cd0.96Zn0.04Te was hydrogenated, the intensity of the exciton luminescence increased so that the (eA°) and DAP peaks related to the Cd vacancies disappeared, and the defect band in the low energy range between 1.4 and 1.5 eV also vanished. These results indicate that hydrogen atoms passivated not only shallow donors but also deep acceptor impurities and that the hydrogen atoms were separated from the hydrogenated samples at 400 °C due to their thermal energy.

Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing

Although the wound healing effects of nitric oxide (NO) are known, the mechanism by which NO modulates corneal wound healing remains unclear. In this study, we investigated the effect of exogenous NO donor (NaNO2) on corneal wound healing. We found that NaNO2 (0.1 μM to 100 μM) increased human corneal epithelial cell (HCEC) viability and migration. It also modulated the phosphorylation of mitogen-activated protein kinases (MAPKs) in a time- dependent manner in those HCECs. Further, p38 MAPK phosphorylation increased at 6 h and normalized at 24 h, while the phosphorylation of extracellular signal regulated kinase (ERK) was increased both at 6 h and 24 h. Topical treatment with NaNO2 (10 μM) enhanced corneal epithelial healing and decreased corneal opacity in murine corneal alkali burn model by modulating inflammatory cytokines. Our findings suggest that NO increased HCEC proliferation and migration via time-dependent MAPK activation and eventually enhanced corneal recovery from the alkali burn.

An Evaluation of the in vivo Safety of Nonporous Silica Nanoparticles: Ocular Topical Administration versus Oral Administration

Nonporous silica nanoparticles (SiNPs) have potential as promising carriers for ophthalmic drugs. However, the in vivo safety of ocular topical SiNPs remains unclear. This study investigated the in vivo safety of oral and ocular topical applications of 100 nm-sized SiNPs in Sprague-Dawley rats. The rats were divided into the following four groups: low-dose oral administration (total 100 mg/kg of SiNPs mixed with food for one week), high-dose oral administration (total 1000 mg/kg of SiNPs mixed with food for one week), ocular topical administration (10 mg/ml concentration, one drop, applied to the right eyes four times a day for one month), or a negative control (no SiNP treatment). The rats were observed for 12 weeks to investigate any signs of general or ocular toxicity. During the observation period, no differences were observed in the body weights, food and water intakes, behaviors and abnormal symptoms of the four groups. No animal deaths occurred. After 12 weeks, hematologic, blood biochemical parameters and ophthalmic examinations revealed no abnormal findings in any of the animals. The lack of toxicity of the SiNPs was further verified in autopsy findings of brain, liver, lung, spleen, heart, kidneys, intestine, eyeballs, and ovaries or testes.

Dependence of the optical properties of p‐CdTe and p‐Cd0.96Zn0.04Te on the bromine concentration in a bromine‐methanol etching solution

Photoluminescence measurements were carried out to investigate the dependence of the optical properties of p‐CdTe and p‐Cd0.96Zn0.04Te on various relative concentrations of bromine in a mixture of methanol and bromine. As the bromine concentration increased, the intensity of the luminescence increased; additionally, an exciton bound to a neutral acceptor (A°X) peak at 1.588 eV in p‐CdTe was resolved into an exciton bound to neutral donor (D°X) peak at 1.592 eV and an A°X peak. The mixed bands of the 1.574 and 1.546 eV peaks were well resolved by using an etching bromine concentration of 2%; in particular, the intensities of the D°X and 1.574 eV peaks increased as much as five and seven times, respectively. The intensity of the peak at 1.48 eV related to defects also increased. The intensity of A°X at 1.609 eV in p‐Cd0.96Zn0.04Te changed slightly with the bromine concentration. The intensities of the luminescence peaks due to the recombination of the electrons in conduction band with acceptors and to the defect relation did not vary. These results indicated that the number of Cd vacancies could be reduced due to the addition of Zn.

Safety of Nonporous Silica Nanoparticles in Human Corneal Endothelial Cells

Nonporous silica nanoparticles (SiNPs) are promising drug carrier platforms for intraocular drug delivery. In this study, we investigated the safety of three different sizes of SiNPs (50, 100, and 150 nm) in a human corneal endothelial cell (HCEC) line, B4G12. The HCECs were exposed to different concentrations (0, 25, 50, and 100 µg/ml) of three sizes of SiNPs for up to 48 h. Cellular viability, autophagy, lactate dehydrogenase (LDH) assay, and mammalian target of rapamycin (mTOR) pathway activation were evaluated. Intracellular distribution of the SiNPs was evaluated with transmission electron microscopy (TEM). TEM revealed that the SiNPs were up-taken by the HCECs inside cytoplasmic vacuoles. No mitochondrial structural damage was observed. Both cellular viability and LDH level remained unchanged with up to 100 µg/mL of SiNP treatment. Autophagy showed a significant dose-dependent activation with 50, 100, and 150 nm SiNPs. However, the mTOR activation remained unchanged. Human corneal tissue culture with 100 µg/ml concentrations of SiNPs for 72 h revealed no significant endothelial toxicity. In vivo corneal safety of the SiNPs (0.05 ml intracameral injection, 200 mg/ml concentration) was also verified in rabbit models. These findings suggested that 50, 100, and 150 nm SiNPs did not induce acute significant cytotoxicity in corneal endothelial cells at concentrations up to 100 µg/mL. However, long-term toxicity of SiNPs remains unknown.

Change of β-Zone Parapapillary Atrophy During Axial Elongation: Boramae Myopia Cohort Study Report 3

Purpose To investigate changes of β-zone parapapillary atrophy (PPA) during axial elongation. Methods Change of β-zone PPA was evaluated by spectral-domain optical coherence tomography (SD-OCT) in myopic children for 2 years, prospectively. Using the infrared images acquired by a fixed scan circle in the glaucoma progression analysis (GPA) mode, the retinal pigment epithelial opening (RPEO) and the clinical disc margin (CDM) were manually delineated. The area and position of β-zone PPA was calculated as the differences from those of the RPEO and CDM, respectively. The β-zone PPA was further differentiated into βBM PPA (β-zone PPA with Bruchs membrane [BM]) and γ-zone PPA (β-zone PPA without BM). The change of β-zone PPA was compared between the first and final visits. Results The area of β-zone PPA increased in 35 eyes (76%). This increase was associated with RPEO area increase and CDM area decrease. The center of β-zone PPA moved along the direction of vascular trunk dragging, but to a lesser extent. The β-zone PPA enlargement was correlated with the extent of vascular trunk dragging (P = 0.014). In all eyes with β-zone PPA increase, the γ-zone portion had increased. Even in childhood, βBM PPA existed next to their γ-zone PPA in 11 eyes (24%), including 4 eyes that showed increase of both γ-zone and βBM portion during axial elongation. Conclusions Enlargement of β-zone PPA during axial elongation was affected by the extent and direction of vascular trunk dragging, thus implicating disproportionate growth between the retina and sclera.

Effect of Nitric Oxide on Acanthamoeba castellanii

Purpose Acanthamoeba keratitis is a well-known intractable corneal infectious disease. We investigated the anti-Acanthamoeba effect of exogenous nitric oxide (NO). Methods Acanthamoeba castellanii was axenically cultured and exposed to various concentrations of NO donors, such as sodium nitrite, sodium nitroprusside (SNP), and NO-releasing silica nanoparticles (coated in branched polyethylene imine, size:100 nm), for 1 to 7 days (sodium nitrite and SNP: 0, 0.1, 1, 10, 100, and 1000 μM; silica nanoparticles: 0, 6.25, 12.5, 25, 50, and 100 μg/mL). Human corneal epithelial cells (HCECs) were cultured and exposed to sodium nitrite, SNP (0, 0.1, 1, 10, 100, and 1000 μM), and silica nanoparticles for 1, 2, and 3 days. Results Sodium nitrite and SNP showed a dose-dependent inhibitory effect on A. castellanii viability. A more prominent inhibitory effect was observed with SNP (less than 10% of organisms survived at 7-day culture with 1000 μM) compared with sodium nitrite. However, more cytotoxicity on HCEC was observed with SNP. NO-releasing silica nanoparticles were successfully internalized into the amoebic cytoplasm and accumulated in large vacuoles. Although blank silica nanoparticles had no inhibitory effect on A. castellanii viability, NO-releasing silica nanoparticles showed a dose-dependent amoebicidal effect. Furthermore, no cystic transformation of A. castellanii was observed under a phase contrast microscope or transmission electron microscope after exogenous NO treatment. Conclusions Our results demonstrated the anti-Acanthamoeba effect of exogenous NO. This finding suggests that NO-releasing drug platforms, including nano-carriers, can be a promising therapeutic strategy for Acanthamoeba keratitis.