Lian Cui

Effect of Topical 5-Aminoimidazole-4-carboxamide-1-β-d-Ribofuranoside in a Mouse Model of Experimental Dry Eye.

PURPOSE To investigate the efficacy of topical 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) in a mouse model of experimental dry eye (EDE). METHODS Eye drops consisting of 0.001% or 0.01% AICAR, 0.05% cyclosporine A (CsA), or balanced salt solution (BSS) were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after treatment. Levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interferon gamma-induced protein 10 (IP-10), and monokine induced by interferon-γ (MIG) were measured in the conjunctiva. In addition, Western blot, periodic acid-Schiff staining for evaluating goblet cell density, flow cytometry for counting the number of CD4+CXCR3+ T cells, and immunohistochemistry for detection of 4-hydroxy-2-nonenal (4HNE) were performed. RESULTS Mice treated with 0.01% AICAR showed a significant improvement in all clinical parameters compared with the EDE control, vehicle control, and 0.001% AICAR groups (P < 0.001). A significant decrease in the levels of IL-1β, IL-6, TNF-α, IFN-γ, IP-10, and MIG, the number of CD4+CXCR3+ T cells, and the number of 4HNE-positive cells were also observed in the 0.01% AICAR group (P < 0.001). Although 0.05% CsA also led to an improvement in clinical parameters and inflammatory molecule levels, its therapeutic effects were comparable or inferior to those of 0.01% AICAR. CONCLUSIONS Topical application of 0.01% AICAR can markedly improve clinical signs and decrease inflammation in the ocular surface of EDE, suggesting that AICAR eye drops may be used as a therapeutic agent for dry eye disease.

Therapeutic Efficacy of Topically Applied Antioxidant Medicinal Plant Extracts in a Mouse Model of Experimental Dry Eye

Purpose. To investigate the therapeutic effects of topical administration of antioxidant medicinal plant extracts in a mouse model of experimental dry eye (EDE). Methods. Eye drops containing balanced salt solution (BSS) or 0.001%, 0.01%, and 0.1% extracts were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after desiccating stress. In addition, we evaluated the levels of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, IL-6, interferon- (IFN-) γ, and IFN-γ associated chemokines, percentage of CD4+C-X-C chemokine receptor type 3 positive (CXCR3+) T cells, goblet cell density, number of 4-hydroxy-2-nonenal (4-HNE) positive cells, and extracellular reactive oxygen species (ROS) production. Results. Compared to the EDE and BSS control groups, the mice treated with topical application of the 0.1% extract showed significant improvements in all clinical parameters, IL-1β, IL-6, TNF-α, and IFN-γ levels, percentage of CD4+CXCR3+ T cells, goblet cell density, number of 4-HNE-positive cells, and extracellular ROS production (P < 0.05). Conclusions. Topical application of 0.1% medicinal plant extracts improved clinical signs, decreased inflammation, and ameliorated oxidative stress marker and ROS production on the ocular surface of the EDE model mice.

Anti-Inflammatory and Antioxidative Effects of Camellia japonica on Human Corneal Epithelial Cells and Experimental Dry Eye: In Vivo and In Vitro Study

Purpose To analyze the anti-inflammatory and antioxidative effects of Camellia japonica (CJ) on human corneal epithelial (HCE) cells and its therapeutic effects in a mouse model of experimental dry eye (EDE). Methods Camellia japonica extracts of varying concentrations (0.001%, 0.01%, and 0.1%) were used to treat HCE cells. Dichlorofluorescein diacetate (DCF-DA) and dihydroethidium (DHE) assays were performed. The production of peroxiredoxin (PRX) 1-6 and manganese-dependent superoxide dismutase (MnSOD) in HCE cells was assessed using Western blot analysis. Furthermore, eye drops containing 0.001%, 0.01%, or 0.1% CJ extract or a balanced salt solution (BSS) were applied to the EDE. Clinical parameters were measured 7 days after treatment. The levels of inflammatory markers and intracellular reactive oxygen species (ROS) were measured. Results Treatment with 0.01% and 0.1% CJ extracts decreased apoptosis in HCE cells. In addition, band intensities of PRX 1, 4, and 5, as well as MnSOD, after hydrogen peroxide (H2O2) treatment showed a significant improvement after pretreatment with 0.01% and 0.1% CJ extracts. Mice treated with 0.1% CJ extract showed significantly improved clinical parameters when compared to those of the EDE control and BSS groups. A significant decrease in the levels of inflammatory markers and intracellular ROS was observed in the 0.01% and 0.1% CJ extract groups. Conclusions Camellia japonica extracts promoted antioxidative protein expression and suppressed apoptosis in HCE cells. Furthermore, CJ extracts improved clinical signs of dry eye and reduced oxidative stress and the expression of inflammatory markers, suggesting that eye drops containing CJ extract could be used as an adjunctive treatment for dry eye.

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.

Experimental and Clinical Applications of Chamaecyparis obtusa Extracts in Dry Eye Disease

Purpose To investigate the effects of Chamaecyparis obtusa (CO) on human corneal epithelial (HCE) cells, a murine experimental dry eye (EDE) model, and the efficacy of antioxidant eye mask in dry eye disease (DED) patients. Methods 0.001%, 0.01%, and 0.1% CO extracts were used to treat HCE cells, cell viability, and production of antioxidative enzymes, and reactive oxygen species (ROS) were assessed. Afterwards, CO extracts or balanced salt solution (BSS) was applied in EDE. Clinical and experimental parameters were measured at 7 days after treatment. In addition, DED patients were randomly assigned to wear either an eye mask containing CO extracts or a placebo. Clinical parameters were evaluated. Results The viability of HCE cells and antioxidative enzyme expression significantly improved after treatment with 0.1% CO extracts. Mice treated with 0.1% CO extracts showed significant improvement in clinical parameters. During the trial, the clinical parameters significantly improved in the treatment group at 4 weeks after application. Conclusions 0.1% CO extracts could promote the expression of antioxidative proteins and ROS production. In addition, an eye mask containing CO extracts could improve DED clinical parameters. These suggest that CO extracts may be useful as an adjunctive option for the DED treatment.

Comparison of 0.3% Hypotonic and Isotonic Sodium Hyaluronate Eye Drops in the Treatment of Experimental Dry Eye

ABSTRACT Purpose: To compare the efficacy of 0.3% hypotonic and isotonic sodium hyaluronate (SH) eye drops in the treatment of experimental dry eye. Methods: Experimental dry eye was established in female C57BL/6 mice by subcutaneous scopolamine injection and an air draft. The mice were divided into three groups (n = 15): control, preservative-free 0.3% isotonic SH, and preservative-free 0.3% hypotonic SH. The tear volume, tear film break-up time, and corneal fluorescein staining scores were measured 5 and 10 days after treatment. After conjunctival tissues were excised at 10 days, the levels of interleukin (IL)-6, IL-17, interferon (IFN)-γ, and IFN-γ inducible protein-10 were determined using the multiplex immunobead assay. In addition, PAS staining and flow cytometry were performed to evaluate the counts of conjunctival goblet cells and CD4+ IFN-γ+ T cells. Results: Mice treated with 0.3% hypotonic SH showed a significant decrease in corneal staining scores (P = 0.04) and the levels of IL-6 (16.7 ± 1.4 pg/mL, P = 0.02) and IFN-γ (46.5 ± 11.5 pg/mL, P = 0.02) compared to mice treated with 0.3% isotonic SH (IL-6; 32.5 ± 8.8 pg/mL, IFN-γ; 92.0 ± 16.0 pg/mL) at day 10. Although no significant difference in CD4+ IFN-γ+ T cell numbers was observed, goblet cell counts were higher in the hyopotonic SH group than in the isotonic SH group (P = 0.02). Conclusions: When compared to 0.3% isotonic SH eye drops, 0.3% hypotonic SH eye drops can be more effective by improving corneal staining scores, decreasing inflammatory molecules, and increasing goblet cell counts for experimental dry eye. These data suggest that hypotonic artificial tears may be useful as an adjunctive treatment for inflammatory dry eye.

Correction: Influence of Light Emitting Diode-Derived Blue Light Overexposure on Mouse Ocular Surface

[This corrects the article DOI: 10.1371/journal.pone.0161041.].

Factors Affecting the Accuracy of Intraocular Lens Power Calculation with Lenstar

This retrospective study was performed to compare refractive outcomes measured by conventional methods and by use of the Lenstar biometer and to investigate the factors affecting intraocular lens (IOL) power calculation with Lenstar with and without IOL-constant optimization. The study included 100 eyes of 86 patients who underwent cataract surgery. Corneal curvature was measured with a manual keratometer (MK), automated keratometer (AK), and the Lenstar biometer, and axial length (AL) was measured by A-scan and Lenstar. Mean numerical error (MNE) and mean absolute error (MAE) were compared between AK and MK with A-scan, and Lenstar with and without optimization. Factors affecting the accuracy of the IOL power calculation by use of Lenstar with and without optimization were analyzed. No significant differences were observed in the MNE or MAE among the devices. The proportion of MAE within 0.5 D was higher for Lenstar with optimization (62.7%) than without optimization (46.2%). The proportion of MAE within 0.5 D was 62% and 58% for MK and AK with A-scan, respectively. Without optimization, the MAE was smaller in eyes with ALs between 23 mm and 25 mm (p=0.03), whereas it was smaller at higher corneal powers when the IOL constant was optimized (>44 D, p=0.03). The IOL power calculations showed no significant differences among the devices, but the results of MAE within 0.5 D by use of Lenstar without optimization were worse than those of conventional methods. The AL influenced the accuracy of refractive outcomes determined by using Lenstar without optimization, and corneal curvature was shown to affect the accuracy of refractive measurements using Lenstar with optimization.