Alterations of aqueous humor Aβ levels in Aβ-infused and transgenic mouse models of Alzheimer disease

Alzheimer's disease (AD) is an ageing-related neurodegenerative disease characterized and diagnosed by deposition of insoluble amyloid-β (Aβ) plaques in the brain. The plaque accumulation in the brain directly affects reduced levels of Aβ in cerebrospinal fluid (CSF) and blood, as Aβ can freely transport the blood-brain barrier, and clinical investigations have suggested these two biofluids as promising samples for in vitro diagnosis. Given that the human eye structurally resembles the brain and Aβ accumulation often observed in the ocular region of AD patients, in this study, we examined aqueous humor Aβ as another possible surrogate biomarker. First, using the acute Aβ-infused AD mouse model by injecting Aβ to the CSF in intracerebroventricular region of normal ICR mice, we investigated whether Aβ concentration in the aqueous humor in AD models is positively correlated with the concentration in the CSF. Then, we examined the correlation of aqueous humor Aβ levels with increased plaque deposition in the brain and reduced Aβ levels in both CSF and blood in adult and aged 5XFAD Alzheimer transgenic mice. Collectively, the synthetic Aβ injected into CSF immediately migrate to the aqueous humor, however, the age-dependently reducing pattern of Aβ levels in CSF and blood was not observed in the aqueous humor.ope

Interleukin-22 Induces the Infiltration of Visceral Fat Tissue by a Discrete Subset of Duffy Antigen Receptor for Chemokine-Positive M2-Like Macrophages in Response to a High Fat Diet.

Interleukin-22 (IL-22) is a cytokine with important functions in host defense and inflammatory responses and has recently been suggested to play a role in immune-inflammatory system in the context of obesity and its metabolic consequences. The specific cellular targets and mechanisms of IL-22-mediated obesity are largely unknown however. We here identified a previously unknown subset of monocyte-derived Duffy antigen receptors for chemokines (DARC)+ macrophages in epididymal fat adipose tissue and found that they are preferentially recruited into the crown-like structures of adipose tissue in the mouse upon high fat diet-induced obesity. Importantly, DARC+ macrophages highly express the IL-22 receptor (IL-22Ra1). Exposure to recombinant IL-22 shifts macrophages to an alternative M2 polarization pathway and augments DARC expression via a STAT5b signaling axis. STAT5b directly binds to the DARC promoter and a STAT5 inhibitor abrogates the IL-22-mediated induction of DARC. These M2-like DARC+ subpopulations of monocytes/macrophages were elevated in obese db/db mice compared to WT lean mice. Furthermore, subsets of CD14+ and/or CD16+ monocytes/macrophages within human peripheral blood mononuclear cell populations express DARC and the prevalence of these subsets is enhanced by IL-22 stimuli. This suggested that IL-22 is a critical cytokine that promotes the infiltration of adipose tissue macrophages, that regulate inflammatory processes. Taken together, our present findings provide important insights into the molecular mechanism by which IL-22 signal modulates DARC expression in M2-like macrophages.ope

Cataract Surgery Practices in the Republic of Korea: A Survey of the Korean Society of Cataract and Refractive Surgery 2018

PURPOSE: To describe current cataract surgery practice patterns and changing trends among Korean ophthalmologists. METHODS: A survey of members of the Korean Society of Cataract and Refractive Surgery was performed in July 2018. One hundred and two (12.7%) of 801 questionnaires were returned for analysis. The data were analyzed using descriptive statistics and compared with previous surveys. RESULTS: Most of the respondents (75%) had been in practice for 6 or more years and performed an average of 31 cataract surgeries per month. The preferred method for cataract surgery was phacoemulsification (95%); 5% used a femtosecond laser. The use of topical anesthesia markedly increased from 69% (2012) to 80% (2018). The use of optical biometry exceeded that of ultrasound A-scan biometry. A multifocal intraocular lens was used by 76% of the respondents compared with 44% of the respondents in 2012. Topical nonsteroidal anti-inflammatory drugs were used by 70% of the respondents postoperatively. Most (59%) of these anti-inflammatory drugs were prescribed for 4 weeks. CONCLUSIONS: This survey provided a comprehensive update of the present cataract surgery practices in the Republic of Korea. The results emphasized the increasing use of premium intraocular lenses, optical biometry, and topical anesthesia.ope

Effects of Preservative-free 3% Diquafosol in Patients with Pre-existing Dry Eye Disease after Cataract Surgery: A Randomized Clinical Trial

Dry eye disease (DED) after cataract surgery has become a critical concern, and various therapeutic options have been developed. Recently, preservative-free diquafosol ophthalmic solution has been introduced; however, its therapeutic effect on DED after cataract surgery has not been reported. We investigated the efficacy of preservative-free diquafosol in patients with pre-existing DED after cataract surgery. We divided subjects who were diagnosed with DED and scheduled to undergo cataract surgery, into 3 groups (preservative-free diquafosol, group 1; preservative-containing diquafosol, group 2; preservative-free hyaluronate, group 3), and each eye drops was administered 6 times daily after surgery. Tear break up time (TBUT), Ocular Surface Disease Index (OSDI), corneal staining score, lid margin abnormality, and meibum quality improved over time in group 1. Groups 1 and 2 had significantly superior TBUT, meibomian gland dysfunction grade, and meibomian gland expressibility throughout the study period than group 3. Meibum quality of group 1 was significantly better than group 2 at 1 and 3 months after surgery. Preservative-free diquafosol showed better efficacy in treating DED after cataract surgery than preservative-containing diquafosol or preservative-free hyaluronate. Preservative-free diquafosol may serve as a reliable option for the management of patients with pre-existing DED after phacoemulsification.ope

Characterization of Circulating IL-7R Positive Cell Populations for Early Detection of Pancreatic Ductal Adenocarcinoma

Background: Pancreatic cancer is a high devastating disease with the lowest survival rate among all common cancers due to difficulties in early diagnosis. The purpose of this study was to identify and characterize the distinct subset of blood cell population elevated in peripheral blood mononuclear cells (PBMC) of pancreatic cancer to evaluate the potential markers for diagnosis of pancreatic cancer; (2) Methods: We analyzed differential gene expression in PBMC from normal individuals and pancreatic cancer patients utilizing transcriptome analysis. Flow cytometry analysis was applied to identify the discrete subset of interleukin-7 receptor (IL-7R) expressing cells in these cells. The expression of IL-7R during tumorigenesis was determined in syngeneic mouse model of pancreatic cancer in vivo; (3) Results: PBMC from pancreatic cancer patients expressed elevated IL-7R mRNA compared to healthy control individuals. IL-7R expressing cells rapidly appeared from the early stages of the onset of tumor formation in syngeneic pancreatic cancer mouse model in vivo. The discrete subset of IL-7R positive cells mainly consist of naive T, central memory T, and effector memory T cells; (4) Conclusions: Taken together, our present findings suggest that pancreatic cancer patients expressed higher level of IL-7R expression in PBMC that rapidly emerged from the onset of early pancreatic tumor formation in vivo than normal individuals. Thus, it can be used as a novel biological marker for early events of pancreatic cancer development.ope

A novel pro-lymphangiogenic function for Th17/IL-17

Th17 cells, in addition to their proinflammatory functions, have been recognized as potent inducers of angiogenesis in autoimmune diseases and malignancies. In the present study, we demonstrate distinct mechanisms by which IL-17 induces lymphangiogenesis. Using the mouse cornea micropocket and cell culture assays, our data demonstrate that IL-17 directly promotes growth of lymphatic vessels by inducing increased expression of prolymphangiogenic VEGF-D and proliferation of lymphatic endothelial cells. However, IL-17-induced growth of blood vessels is primarily mediated through IL-1β secretion by IL-17-responsive cells. Furthermore, in vivo blockade of IL-17 in a preclinical model of Th17-dominant autoimmune ocular disease demonstrates a significant reduction in the corneal lymphangiogenesis and in the progression of clinical disease. Taken together, our findings demonstrate a novel prolymphangiogenic function for Th17/IL-17, indicating that IL-17 can promote the progression and amplification of immunity in part through its induction of lymphangiogenesis.ope

Comparison of Contact Lens Corrected Quality of Vision and Life of Keratoconus and Myopic Patients

PURPOSE: To compare and analyze changes in vision quality, subjective symptoms, and psycho-social satisfaction in keratoconus and myopic patients following the wearing of contact lenses. METHODS: This study enrolled 25 keratoconus and 25 myopic patients with corrected vision over 0.8 according to the Snellen chart due to treatment with contact lenses. Patients were surveyed prior to the wearing of contact lenses, and again after three months of contact lens usage with a questionnaire about quality of vision and life. The changes in visual function, visual symptoms, and psycho-social well-being before and after contact lens usage were analyzed. RESULTS: The keratoconus patients' overall degree of satisfaction was higher than the overall degree of satisfaction of myopic patients, and the motivation for contact lens usage and purpose of contact lens treatment were different in the two groups. Keratoconus patients experienced greater changes in satisfaction, particularly in satisfaction during night activities, short-distance work, and the reading of fine print. Furthermore, they experienced fewer dry eye symptoms but greater foreign body sensations than patients with myopia following treatment with contact lenses. No statistically significant differences in social role functions existed between the two groups. Keratoconus patients had a lower expectation of visual acuity recovery before treatment with contact lenses (Mann-Whitney U-test, p = 0.049) compared to myopic patients, and more anxiety about vision loss following treatment (Wilcoxon signed-rank test, p = 0.018) compared to their level of anxiety about vision loss before treatment with contact lenses. CONCLUSIONS: Although the same treatment was applied, keratoconus and myopic patients experienced different types of discomfort and areas of improvement in contact lens corrected vision. Therefore, not only corrected vision, but also subsequent improvement and discomfort outcomes should be considered by patients when choosing contact lens treatment. For patients with mild keratoconus, contact lens treatment may be an efficacious first treatment modality.ope

Analysis of the Cause of Failure in the Correction of Childhood Myopia Using Orthokeratologic Lenses

Purpose: To investigate the cause of failure in the correction of childhood myopia using orthokeratologic (Ortho-K) lenses. Methods: The failure group was 29 patients who stopped wearing the lenses for various reasons, while the success group was 29 patients who bought lenses more than twiceand wore them for two years and more. Statistical analyses were performed to identify significant differences between the groups. Results: Among the failure group, failure to continuously wear the Ortho-K lenses was attributed to undercorrection (19 patients), corneal erosion (2 patients), and sleep disorders (1 patient). Initial spherical diopter and initial spherical equivalent diopter showed statistical diffence between the success group and failure group. Of these two factors, as the initial spherical equivalent diopter increased, the chance of failure to use Ortho-K lens increased. According to a logistic multiple regression analysis, the odds of failure of using Ortho-K lens increased by 1.59 when the initial spherical diopter increased by 1. If the absolute value of the initial spherical diopter was over 6.24, the chance of failure increased by 80%. Conclusions: The failure of continuously wearing Ortho-K lenses due to undercorrection was found to be the major cause of failure in the correction of childhood myopia. The initial spherical diopter and initial spherical equivalent diopter were significant factors influencing the undercorrection. From these results, we predict that the odds of failure of continuously wearing Ortho-K lenses increases along with increases in the initial spherical diopter. In conclusion, clinicians should be warned concerning the odds of failure due to low initial spherical diopter.ope

Corneal Lymphangiogenesis: Current Pathophysiological Understandings and Its Functional Role in Ocular Surface Disease

The cornea is a transparent and avascular tissue that plays a central role in light refraction and provides a physical barrier to the external environment. Corneal avascularity is a unique histological feature that distinguishes it from the other parts of the body. Functionally, corneal immune privilege critically relies on corneal avascularity. Corneal lymphangiogenesis is now recognized as a general pathological feature in many pathologies, including dry eye disease (DED), corneal allograft rejection, ocular allergy, bacterial and viral keratitis, and transient corneal edema. Currently, sizable data from clinical and basic research have accumulated on the pathogenesis and functional role of ocular lymphangiogenesis. However, because of the invisibility of lymphatic vessels, ocular lymphangiogenesis has not been studied as much as hemangiogenesis. We reviewed the basic mechanisms of lymphangiogenesis and summarized recent advances in the pathogenesis of ocular lymphangiogenesis, focusing on corneal allograft rejection and DED. In addition, we discuss future directions for lymphangiogenesis research.ope

SIRT1 Protects Against Particulate Matter-Induced Oxidative Stress in Human Corneal and Conjunctival Epithelial Cells

Purpose: Sirtuin1 (SIRT1) as a hot therapeutic target for oxidative stress-associated diseases that has been extensively studied. This study aimed to determine the changes in SIRT1 expression in particulate matter (PM)-induced corneal and conjunctival epithelial cell damage and explore potential drugs to reduce PM-associated ocular surface injury. Methods: Immortalized human corneal epithelial cells (HCECs) and human conjunctival epithelial cells (HCjECs) were exposed to an ambient PM sample. Cytotoxicity was evaluated by water-soluble tetrazolium salt-8 assay. SIRT1 expression was measured by Western blot analysis. Reactive oxygen species (ROS) production, cell apoptosis, mitochondrial function, and cell senescence were assessed by using 2',7'-dichlorofluorescein diacetate assay, annexin V apoptosis assay, tetramethylrhodamine ethyl ester assay, and senescence β-galactosidase staining, respectively. Results: PM-induced cytotoxicity of HCECs and HCjECs occurred in a dose-dependent manner. Increased ROS production, as well as decreased SIRT1 expression, were observed in HCECs and HCjECs after 200 µg/mL PM exposure. In addition, PM induced oxidative stress-mediated cellular damage, including cell apoptosis, mitochondrial damage, and cell senescence. Interestingly, SRT1720, a SIRT1 activator, increased SIRT1 expression and decreased ROS production and attenuated PM-induced cell damage in HCECs and HCjECs. Conclusions: This study determined that SIRT1 was involved in PM-induced oxidative stress in HCECs and HCjECs and found that ROS overproduction may a key factor in PM-induced SIRT1 downregulation. The SIRT1 activator, SRT1720, can effectively upregulate SIRT1 expression and inhibit ROS production, thereby reversing PM-induced cell damage. This study provides a new potential target for clinical treatment of PM-associated ocular surface diseases.ope