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We investigated the time-dependent deleterious ocular changes induced by urban particulate matter (UPM) in vitro and in vivo. UPM treatment decreased human corneal epithelial cell migration and survival. Fluorescein scores were consistently increased by UPM application for 16 weeks. One week of rest at 2 or 4 weeks led to a recovery trend, whereas two weeks of rest at 8 weeks induced no change. UPM treatment decreased the tear film break-up time at 2 weeks, which was thereafter maintained until 16 weeks. No changes were found after periods of rest. UPM-treated eyes exhibited greater corneal epithelium thickness than normal eyes at 2 weeks, which recovered to normal at 4 and 8 weeks and was significantly decreased at 16 weeks. Apoptotic cell number in the epithelium was increased at 2 weeks, which remained constant except at 8 weeks. IL-6 expression in the cornea of the right eye continually increased for 16 weeks, and significant recovery was only observed at 8 weeks after 2 weeks of rest. Ocular pressure was significantly increased in the right eye at 12 and 16 weeks. Topical UPM application to the eye induced deleterious changes to various closely related parts of the eye.

We previously demonstrated that urban particulate matter (UPM) exposure decreases the migration activity and survival of human corneal epithelial cells (HCECs). Herein, we investigated the potential to improve the corneal wound-healing ability of Peucedanum japonicum Thunb. leaf extract (PJE) and its active components on UPM-induced ocular surface damage in vitro and in vivo. PJE effectively assisted wound healing without altering HCEC survival and enhanced catalase (CAT), heme oxygenase 1 (HO1) and glutathione peroxidase 1 (GPX1) antioxidant gene expression. A corneal wound was uniformly induced on the right eye in all experimental animals and divided into eight groups such as two control groups (wounded right eye group—NR and non-wounded left eye group—NL), UPM treated group and PJEs (25, 50, 100, 200, 400 mg/kg) treated groups. Corneal abrasion model rats exposed to UPM showed delayed wound healing compared to unexposed rats, but wound healing was dose-dependently enhanced by PJE oral administration. Seventy-two hours after wound generation, inflammatory cells, apoptotic cells and interleukin-6 (IL-6) expression were increased substantially after UPM exposure, but PJE treatment significantly reduced the wound to an almost normal level while enhancing re-epithelialization without changing corneal thickness. Next, we tried to identify the key molecules for enhancing wound healing through fractionation. The major compounds in the fraction, confirmed by high-performance liquid chromatography (HPLC), were chlorogenic acid (CA), neochlorogenic acid (NCA) and cryptochlorogenic acid (CCA). Each type of CA isomers showed slightly different half maximal effective (EC50) and maximal effective (ECmax) concentrations, and their mixtures synergistically enhanced HCEC migration. Thus, corneal abrasion wound recovery after UPM exposure improved after PJE treatment, and the active PJE components were identified, providing an important basis to develop therapeutics for ocular surface damage using PJE. [ABSTRACT FROM AUTHOR]

Dry eye disease is affected by a broad range of causes such as age, lifestyle, environment, medication and autoimmune diseases. These causes induce tear instability that activates immune cells and promotes expression of inflammatory molecules. In this study, we investigated the therapeutic effects of an ethanolic extract of Aucuba japonica (AJE) and its bioactive compound, aucubin, on dry eye disease. The human corneal cells were exposed to desiccation stress induced by exposing cells to air, so that viability was decreased. On the other hand, pre-treatment of AJE and aucubin restored cell survival rate depending on the dose under the dry condition. This result was confirmed again by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The mRNA expression of inflammatory molecules was reduced by the pretreatment of AJE and aucubin under the dry state. The therapeutic effects of AJE and aucubin were examined in the animal model for dry eye induced by unilateral excision of the exorbital lacrimal gland. Declined tear volumes and corneal irregularity in the dry eye group were fully recovered by the administration of AJE and aucubin. The apoptotic cells on the cornea were also decreased by AJE and aucubin. Therefore, this study suggests that administration of AJE can be a novel therapeutic for dry eye disease and that the pharmacological activities of AJE may be in part due to its bioactive compound, aucubin. [ABSTRACT FROM AUTHOR]