Bongkyun Park

Introduction: Dry eye disease (DED) is a very frequently encountered ocular disease, making it a growing public health burden. However, current treatments for DED present unmet medical needs owing to their side effects or ineffectiveness. Therefore, an effective and safe therapeutic agent to manage DED is needed. Method and Analysis: We planned a phase 2, dose-finding, double-blind, randomized placebo-controlled trial to evaluate the efficacy and safety of two different doses of USL (Useul), the extract of Achyranthis Radix, compared with placebo, for DED. USL has been found to protect against DED by inducing tear secretion and improving corneal irregularity via anti-inflammatory effects, which will provide new therapeutic options. One hundred and twenty participants will be enrolled, after assessing the inclusion/exclusion criteria, at Daejeon University Daejeon Korean Medicine Hospital. Enrolled participants will be allocated to standard-dose USL, high-dose USL, or placebo groups in a 1:1:1 ratio and will be required to administer the trial medication twice a day for 12 weeks and visit the clinic five times. For efficacy outcomes, objective endpoints of fluorescein corneal staining score, tear break-up time, Schirmer’s test, and meibomian test and subjective endpoints of Ocular Surface Disease Index, visual analog scale, Standard Patient Evaluation for Eye Dryness-II, and biomarkers will be assessed throughout the trial. Safety will be assessed based on adverse events, vital signs, laboratory tests, visual acuity, and intraocular pressure. Discussion: Our study results are expected to provide clinical evidence for the use of DED as an effective and safe agent for DED.

Particulate matter (PM) is an environmental hazard that is associated with various human health risks. The olfactory system is directly exposed to PM; therefore, the influence of PM exposure on olfactory function must be investigated. In this study, we propose a zebrafish olfactory model to evaluate the effects of exposure to diesel particulate matter (DPM), which was labeled Korean diesel particulate matter (KDP20). KDP20 comprises heavy metals and polycyclic aromatic hydrocarbons (PAHs). KDP20 exposed olfactory organs exhibited reduced cilia and damaged epithelium. Olfactory dysfunction was confirmed using an odor-mediated behavior test. Furthermore, the olfactory damage was analyzed using Alcian blue and anti-calretinin staining. KDP20 exposed olfactory organs exhibited histological damages, such as increased goblet cells, decreased cell density, and calretinin level. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that PAHs exposure related genes (AHR2 and CYP1A) were upregulated. Reactive oxidation stress (ROS) (CAT) and inflammation (IL-1B) related genes were upregulated. Furthermore, olfactory sensory neuron (OSN) related genes (OMP and S100) were downregulated. In conclusion, KDP20 exposure induced dysfunction of the olfactory system. Additionally, the zebrafish olfactory system exhibited a regenerative capacity with recovery conditions. Thus, this model may be used in future investigating PM-related diseases.

Recently, Achyranthis radix extract has been studied as a therapeutic agent for dry eye disease that occurs from fine dust. The aim of this study was the development of Achyranthis radix extract-loaded eye drop formulations using lubricants, generally used for artificial tear eye drops. Ecdysterone was used as a marker compound for Achyranthis radix extract and 1% Achyranthis radix extract solution contained 14.37 ± 0.04 μg/mL of ecdysterone. Before formulation studies, a new method was performed to evaluate pigmentation, which might be caused by eye drops of herbal extract. A comparative study of the water retention ability of each formulation and ability to prevent the death of conjunctival epithelial cells in dry conditions was conducted. Moreover, treatment of Achyranthis radix extract (USL) eye drop formulation exhibited a significant inhibitory effect on inflammation in a concentration-dependent manner. The long-term and accelerated stability tests showed that lubricants could contribute to the stability of herbal extracts in solution. In conclusion, hyaluronic acid showed a good effect on the development of eye drop formulation using Achyranthis radix extracts for treating dry eye disease.

Polydatin (also named pieceid, (E)-piceid, (E)-polydatin, trans-polydatin, or 3,5,4’-trihydroxystilbene-3-b-D-glucoside) is a monocrystalline compound isolated from the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae). A previous study showed that polydatin has antioxidant and anti-inflammatory effects. However, the effect of polydatin in dry eye disease (DED) has not been elucidated. DED rat models were induced by exorbital lacrimal gland-excision. In vivo, the present study showed that the excision of lacrimal glands induced changes such as reduced tear fluid, severe corneal irregularity, damage, tear film break, and goblet cell loss as well as increased inflammation cytokine and NLRP3 expression in conjunctival tissue. However, these changes were restored by polydatin eye dropping. In vitro, polydatin inhibited hyperosmolar stress-induced inflammation through attenuation of the translocation of NF-κB to the nucleus and the mRNA expression of TNF-α, IL-6, IL-1β, and MMP9. In addition, the hyperosmolar stress-induced NLRP3 inflammasome pathway and ROS production were inhibited by polydatin. Our findings provided insight into the effect of polydatin as a candidate reagent for the treatment of DED.

Dry eye disease (DED) is a multifactorial inflammatory disease that severely impairs patients’ quality of life. Particulate matter comprises a harmful mixture of particles less than 10 μm in size, which on contact with the eye, causes inflammation in the cornea/conjunctival epithelium, threatening eye health and triggering the onset of DED. Achyranthis radix is an ingredient of traditional medicine generally used for treating osteoporosis, trauma, and thrombosis in Asian countries. However, the effect of Achyranthis radix on eye health has not been elucidated. In this study, we evaluate the protective effect of Achyranthis radix hot water extract (ARE) in a rat model of urban particulate matter (UPM)-induced DED. UPM with or without ARE were topically administered on both eyes thrice daily for 10 days. ARE induced tear secretion and improved corneal irregularity. Additionally, ARE treatment protected the corneal epithelial cells from UPM-induced apoptosis. It also restored rMuc4 expression in the cornea and increased goblet cell density in the conjunctiva. These results are suggestive of the potential of ARE as a topical therapeutic agent for treating DED.

Exposure to particulate matter is a risk factor for various ocular surface diseases, including keratoconjunctivitis sicca (KCS). In this study, we investigated the protective effects of apricot kernel extract (AKE) and its bioactive compound, amygdalin, on KCS induced by exposure to urban particulate matter (UPM). In the in vivo experiments, eye drops containing 0.5 mg/mL AKE (AKE-0.5) or 1 mg/mL AKE (AKE-1) were administered directly into the eyes of female rats after UPM exposure. Additionally, the effect of AKE and amygdalin on matrix metalloproteinases (MMPs) activity and the expressions of inflammatory factors, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, was investigated in conjunctival epithelial cells in vitro. Topical administration of AKE-1 attenuated UPM exposure-induced reduction of tear secretion. Both AKE-0.5 and AKE-1 inhibited UPM exposure-induced corneal epithelial damage and irregularity. AKE also protected against UPM exposure-induced disruption of the mucin-4 layer on the ocular surface. In addition, AKE and amygdalin prevented UPM-induced activation of MMPs and upregulation of TNF-α and IL-6 in conjunctival epithelial cells. Therefore, AKE may have protective effects against UPM exposure-induced KCS via the inhibition of MMPs and inflammation. The pharmacological activities of AKE may be in part due to its bioactive compound, amygdalin.

Dry eyes are caused by highly increased osmolarity of tear film, inflammation, and apoptosis of the ocular surface. In this study, we investigated the effect of Polygonum cuspidatum (PCE) aqueous extract in in vivo and in vitro dry eye models. Dry eye was induced by excision of the lacrimal gland and hyperosmotic media. In vivo, oral administration of PCE in exorbital lacrimal gland-excised rats recovered tear volume and Mucin4 (MUC4) expression by inhibiting corneal irregularity and expression of inflammatory cytokines. In vitro, hyperosmotic media induced human corneal epithelial cell (HCEC) cytotoxicity though increased inflammation, apoptosis, and oxidative stress. PCE treatment significantly inhibited expression of cyclooxygenase-2 and inflammatory cytokines (interleukin-6 and tumor necrosis factor-α), and activation of NF-κB p65 in hyperosmolar stress-induced HCECs. Hyperosmolarity-induced increase in Bcl-2-associated X protein (BAX) expression and activation of cleaved poly (ADP-ribose) polymerase and caspase 3 were attenuated in a concentration-dependent manner by PCE. PCE treatment restored anti-oxidative proteins such as heme oxygenase-1 (HO-1), superoxide dismutase-1 (SOD-1), and glutathione peroxidase (GPx) in hyperosmolar stress-induced HCECs. These data demonstrate that PCE prevents adverse changes in the ocular surface and tear fluid through inhibition of hyperosmolar stress-induced inflammation, apoptosis, and oxidation, suggesting that PCE may have the potential to preserve eye health.