Current updates for hyperuricemia and gout in age-related macular degeneration.

The escalating prevalence of metabolic syndrome poses a significant public health challenge, particularly among aging populations, with metabolic dysfunctions contributing to pro-inflammatory states. In this review, we delved into the less recognized association between hyperuricemia (HUA), a manifestation of metabolic syndrome and a primary risk factor for gout, and age-related macular degeneration (AMD), a sight-threatening ailment predominantly affecting the elderly. In recent years, inflammation, particularly its involvement in complement pathway dysregulation, has gained prominence in AMD pathophysiology. The contradictory role of uric acid (UA) in intercellular and intracellular environments was discussed, highlighting its antioxidant properties in plasma and its pro-oxidant effects intracellularly. Emerging evidence suggests a potential link between elevated serum uric acid levels and choroid neovascularization in AMD, providing insights into the role of HUA in retinal pathologies. Various pathways, including crystal-induced and non-crystal-induced mechanisms, were proposed to indicate the need for further research into the precise molecular interactions. The implication of HUA in AMD underscores its potential involvement in retinal pathologies, which entails interdisciplinary collaboration for a comprehensive understanding of its impact on retina and related clinical manifestations.

Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy.

The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial-mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.

Klotho Null Mutation Indirectly Leads to Age-Related Lacrimal Gland Degeneration in Mutant Mice.

The Klotho null mutation is known to lead to accelerated aging in many organs, but its effects on tear secretion and lacrimal gland (LG) senescence have not been addressed. This study investigated whether the Klotho null mutation would lead to a dry eye status and the outcome of LG without Klotho function. The Klotho (-/-) mutant mice showed reduced LG size and tear volume on the 8th week, as compared to their littermates (+/+, +/-). Hematoxylin-Eosin and Masson's trichrome staining were performed to determine morphological changes and collagen deposition. Traits of LG aging, including acinar atrophy, thickened capsules, and more collagen depositions, were observed. Immunohistochemical detections for Klotho, α-SMA, MDA, 8-OHdG, vasoactive intestinal polypeptide (VIP), tyrosine hydroxylase (TH), MMP-2, MMP-9, and FGF-23 were performed and compared among the three genotypes (+/+, +/-, -/-) at 6 and 8 weeks of age for mechanism analyses. Unexpectedly, the Klotho protein was not detected in the LG of all the three genotypes, indicating indirect effects from the Klotho null mutation. Further analyses showed abundant MDA and 8-OHdG detected in the Klotho (-/-) LG on the 8th week, indicating elevated oxidative stress. In addition, both sympathetic and parasympathetic neural transducing activities, as represented by TH and VIP expression, respectively, and α-SMA were increased in LGs with Klotho mutations. Furthermore, MMP-2 and MMP-9 expression were elevated, with FGF-23 expression being decreased on the 8th week in the Klotho (-/-) LG. In conclusion, characteristics of age-related LG degeneration were found in the Klotho null mutant mice. These traits support the use of Klotho mutant mice as a model of age-related dry eye disease.

Preventative Effects of Cordyceps cicadae Mycelial Extracts on the Early-Stage Development of Cataracts in UVB-Induced Mice Cataract Model.

Cataracts, a prevalent age-related eye condition, pose a significant global health concern, with rising rates due to an aging population and increased digital device usage. In Taiwan, cataract prevalence is particularly high, reaching up to 90% among individuals aged 70 and above. The lens of the eye absorbs short-wave light, which can lead to oxidative stress in lens epithelial cells and contribute to cataract formation. Exposure to ultraviolet (UV) light further exacerbates the risk of cataracts by generating reactive oxygen species. Heat-shock proteins (HSPs), involved in protein maintenance and repair, have been linked to cataract development. Cordyceps cicadae (C. cicadae), a traditional Chinese medicine, has a long history of use and is known for its pharmacological effects. N6-(2-hydroxyethyl) adenosine (HEA), a bioactive compound found in C. cicadae, exhibits anti-inflammatory, immunomodulatory, and neuroprotective properties. Previous studies have shown that C. cicadae mycelial extracts improve dry eye disease and reduce intraocular pressure in animal models. Additionally, C. cicadae possesses antioxidant properties, which are beneficial for combating cataract formation. In this study, we aim to evaluate the preventive efficacy of C. cicadae mycelial extracts in UV-induced cataract development. By investigating the ameliorative effects of C. cicadae on eye diseases and its potential role in ocular health improvement, we hope to uncover new options for cataract prevention and provide insights into the mechanisms of action. The findings of this research could provide a novel approach for nutritional supplements targeting cataract prevention, offering potential benefits in the field of ocular health.

Diagnosis of Photokeratitis by Tear Ferning Using a Novel Set of SK Grading Criteria in a UVB-Induced Mouse Model.

Purpose: Current ocular surface diagnostic methods may not totally meet and implement the clinical demands for early and precise treatments. The tear ferning (TF) test has been known as a quick, simple, and inexpensive procedure. This study aimed to validate the TF test as an alternative method for early determination of photokeratitis status. Methods: The tear sample was collected from the UVB-induced photokeratitis eyes and processed for TF formation. The TF patterns were graded by both the Masmali and a Sophie-Kevin (SK) grading criteria, a new set of criteria modified from the Masmali grading, for differential diagnoses. In addition, the TF test results were correlated with three clinical ocular surface indicators, including tear volume (TV), tear film break-up time (TBUT), and cornea staining, to evaluate the diagnostic capacity. Results: Differential diagnosis between the normal and the photokeratitis status was achieved by the TF test. The SK grading reflected earlier photokeratitis status than the Masmali grading criteria. The TF results were strongly correlated with the three clinical ocular surface indicators, particularly for the TBUT and cornea staining. Conclusions: The TF test was proven to have a capacity to distinguish photokeratitis from the normal status at an early stage by using the SK grading criteria. It is therefore potentially useful for photokeratitis diagnosis in the clinical settings. Translational Relevance: The TF test may fulfill the demands of precise and early diagnosis to facilitate in time the intervention for photokeratitis.

Klotho Null Mutation Involvement in Adenosine A2B Receptor-Related Skeletal Muscle Degeneration.

Klotho is known for its age-suppressing function and has been implicated in sarcopenia pathology. It has recently been proposed that the adenosine A2B receptor plays a crucial role in skeletal muscle energy expenditure. However, the association between Klotho and A2B remains elusive. In this study, Klotho knockout mice, aged 10 weeks, and wild-type mice, aged 10 and 64 weeks, were used for comparison in indicators of sarcopenia (n = 6 for each group). PCR was performed to confirm the mice genotypes. Skeletal muscle sections were analyzed using hematoxylin and eosin staining as well as immunohistochemistry staining. The skeletal muscle cross-sectional area was significantly reduced in Klotho knockout mice and wild-type mice, aged 64 weeks, when compared with wild-type mice, aged 10 weeks, with a decreased percentage of type IIa and IIb myofibers. Likely impaired regenerative capacity, as reflected by the reduction of paired box 7 (Pax7)- and myogenic differentiation protein 1 (MyoD)-positive cells, was also observed in Klotho knockout mice and aged wild-type mice. 8-Hydroxy-2-deoxyguanosine expression was enhanced with Klotho knockout and aging, indicating higher oxidative stress. Adenosine A2B signaling was impaired, with a lower expression of the A2B receptor and the cAMP-response element binding protein in Klotho knockout and aged mice. The present study provides the novel finding that sarcopenia involves adenosine signaling under the influence of Klotho knockout.

Efficacy of Cordyceps cicadae (Ascomycota) Mycelium Supplementation for Amelioration of Dry Eye Symptoms: A Randomized, Double-Blind Clinical Pilot Study.

Dry eye disease (DED), a multifactorial inflammatory ocular surface disorder, affects up to 50% of individuals over 50 years old worldwide and is one of the most common reasons for seeking ophthalmologic care. Generally, topical eye drops or oral drugs are administered to treat DED; however, the use of preservatives in eye drops or the adverse effects of oral drugs are disadvantageous for long-term therapy. Cordyceps cicadae, a traditional Chinese medicinal fungus, possesses anti-inflammatory effects without evident toxicity and is obtainable at low price. Our previous study demonstrated that C. cicadae mycelium effectively ameliorates dry eye symptoms in the benzalkonium chloride (BAC)-induced mouse dry eye model by increasing tear volume and tear film breakup time (TBUT). However, the effects of C. cicadae mycelium for human dry eye amelioration remains unknown. Thus, the present study investigated the mitigation of dry eye conditions and related discomforts through oral supplementation of fermented C. cicadae mycelium. A total of 70 healthy individuals were recruited and randomly allocated to receive a daily oral dose of 1,050 mg preparation in sachet containing either freeze-dried C. cicadae mycelium powder with 0.3 mg of adenosine and 1.5 mg of HEA per gram or placebo for 90 days. The participants were subjected to anthropometric measurements, dry eye questionnaires (DEQ), Schirmer's tests, intraocular pressure (IOP) measurements, tear film breakup time (TBUT) tests, tear osmolality measurements, and tear electrolyte analysis prior to and right after completion of the study. The results showed a significantly increased TBUT as well as a significant decrease in tear osmolarity, in parallel with the decrease of tear electrolytes, especially Na+ and Cl ions. Although significant increase of tear volume was not observed, the increased TBUT suggests mitigation of dry eye through improvement of tear quality. Therefore, C. cicadae mycelium supplementation may be used for dry eye alleviation as a novel therapeutic intervention.

Short-Term Hyperuricemia Leads to Structural Retinal Changes That Can be Reversed by Serum Uric Acid Lowering Agents in Mice.

Purpose: Metabolic disorders have been implicated in ocular diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Recently, hyperuricemia (HUA) has been proposed as another risk factor for AMD, although no cause-and-effect experimental data have been published. In this study, we investigated whether HUA would initiate AMD or related retinal damages in hyperuricemic mice. Methods: HUA was induced in male ICR mice by dietary supplements of uric acid and oxonic acid potassium salt, with or without treatments by allopurinol or benzbromarone for various durations. Serum uric acid and angiotensin II concentrations were measured by enzyme-linked immunosorbent assay (ELISA) at regular intervals. The retinal damages were assessed by hematoxylin and eosin staining, immunostaining, and TUNEL assay. The cause-and-effect of HUA was compared among the study groups. Results: The results showed that the total thickness of photoreceptor inner and outer segments, as well as the thickness of the photoreceptor outer segment alone, were reduced under HUA. Furthermore, HUA elevated serum angiotensin II, which indicated activation of the renin-angiotensin system (RAS), leading to higher matrix metalloproteinase-2 (MMP-2) expression, and glial activation in the ganglion cell layer. HUA also led to the reduction of retinal pigment epithelium gap junction protein connexin-43 and apoptosis. Uric acid lowering agents, allopurinol or benzbromarone, were effective in ameliorating the impairments. Conclusions: HUA may pose as a causative factor of retinal injuries. The reduction of serum uric acid may reduce the detrimental effects caused by HUA.

Safety Assessment of HEA-Enriched Cordyceps cicadae Mycelium: A Randomized Clinical Trial.

Objective:Cordyceps cicadae, a medicinal fungus, is assessed as having many functions: anti-cancer, anti-fatigue, anti-aging, immune-boosting, renal and liver protection. Since the industrial production of C. cicadae mycelium consistently manufactures bioactive compounds superior to wild fruiting bodies, there is a need to confirm the toxicity of liquid fermented C. cicadae mycelium. Studies showed the toxicity evaluation of C. cicadae mycelium in animal models, but safety reports in clinical studies are scarce. As such, a safety assessment of oral N6-(2-hydroxyethyl) adenosine (HEA-enriched) C. cicadae mycelium in humans is provided here.Method: After 49 participants ingested granules of 1.05 g of freeze-dried C. cicadae mycelium once a day for 3 months, their blood samples were collected at the beginning and end of the experiment for analysis.Results: There were no significant differences between the initial and final measurements in renal and liver function. Also, there was no influence on blood electrolytes as well as blood lipid levels. In clinical observation, there were also no side effects or adverse feelings mentioned by participants.Conclusion: These results suggested that HEA-enriched C. cicadae mycelium produced by liquid fermentation is safe and can be developed as a functional health food.

Establishment of a Tear Ferning Test Protocol in the Mouse Model.

Purpose: Analysis of ferning formation after tear drop desiccation on a glass slide has been applied as a simple method to examine tear normality and is referred to as the tear ferning (TF) test. Despite use of the TF test in clinical settings and in some animals, thus far no TF test protocol has been developed for the mouse model. This study aimed to establish a mouse TF test protocol that can be used for dry eye research using the mouse as the study model. Methods: Tear samples were collected from 24 healthy mice after repeated flushes with 2, 5, 10, or 20 µL wash solutions, either 0.9% NaCl saline or sterile water, on the ocular surface. After sample collection, TF tests were performed at variable drop volumes (2-20 µL), at a relative humidity of either 46% ± 2% or 53% ± 2%, and with temperature fixed at 24°C ± 2°C for comparison. Moreover, the influence of osmolarity (between 280 and 360 mOsm/L) and pH values (6.5-8.0) and the effect of centrifugation (4000 rpm, 10 minutes) on ferning formation were examined. Reproducibility and ferning storage stability were also determined. Results: An optimized protocol was established with relative humidity at 46% ± 2% and drop aliquot at 2 µL, using 0.9% NaCl saline as the wash solution. Using sterilized water as the wash solution did not result in any crystalloid formation. Centrifugation did not aid ferning formation in any of the samples. Higher osmolarity increased ferning formation from grades between 0 to 1 to grades between 2 to 3, but pH values that varied between 6.5 and 8.0 did not affect ferning formation. The established mouse TF test protocol also displayed reproducibility and storage stability. Conclusions: A TF test protocol for the mouse model was established that could be used for comparative analyses under various ocular surface disease conditions. Translational Relevance: This mouse TF test protocol will facilitate the application of basic research into the mouse model to clinical care.

Prevention of Early Alzheimer's Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study.

OBJECTIVE: To investigate the efficacy and safety of three H. erinaceus mycelia (EAHE) capsules (350 mg/capsule; containing 5 mg/g erinacine A active ingredient) per day for the treatment of patients with mild Alzheimer's Disease (AD). METHODS: This study comprised a 3-week no-drug screening period, followed by a 49-week double-blind treatment period with 2-parallel groups in which eligible patients were randomized to either three 5 mg/g EAHE mycelia capsules per day or identical appearing placebo capsules. Cognitive assessments, ophthalmic examinations, biomarker collection, and neuroimaging were followed throughout the study period. RESULTS: After 49 weeks of EAHE intervention, a significant decrease in Cognitive Abilities Screening Instrument score was noted in the placebo group, a significant improvement in Mini-Mental State Examination score was observed in the EAHE group and a significant Instrumental Activities of Daily Living score difference were found between the two groups. In addition, EAHE group achieved a significantly better contrast sensitivity when compared to the placebo group. Moreover, only the placebo group observed significantly lowered biomarkers such as calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor and significantly elevated alpha1-antichymotrypsin and amyloid-beta peptide 1-40 over the study period. Using diffusion tensor imaging, the mean apparent diffusion coefficient (ADC) values from the arcuate fasciculus region in the dominant hemisphere significantly increased in the placebo group while no significant difference was found in the EAHE group in comparison to their baselines. Moreover, ADC values from the parahippocampal cingulum region in the dominant hemisphere significantly decreased in the EAHE group whereas no significant difference was found in the placebo group when compared to their baselines. Lastly, except for four subjects who dropped out of the study due to abdominal discomfort, nausea, and skin rash, no other adverse events were reported. CONCLUSION: Three 350 mg/g EAHE capsules intervention for 49 weeks demonstrated higher CASI, MMSE, and IADL scores and achieved a better contrast sensitivity in patients with mild AD when compared to the placebo group, suggesting that EAHE is safe, well-tolerated, and may be important in achieving neurocognitive benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04065061.

A Murine Model of Acute Allergic Conjunctivitis Induced by Continuous Exposure to Particulate Matter 2.5.

Purpose: Several pieces of epidemiologic evidence have indicated PM2.5 (particulate matter with a diameter of 2.5 µm or less) as a causing factor of allergic conjunctivitis, but without experimental elucidation of mechanism. In the present study, PM2.5 in solution was directly applied to the mouse ocular surface to elucidate whether PM2.5 might cause allergic conjunctivitis, and its underlying mechanisms were analyzed. Methods: ICR mice were challenged for 18 consecutive days with eye drops containing PM2.5 at 3.2, 6.4, and 12.8 mg/mL in 0.9% NaCl saline, along with the controls prepared in parallel without PM2.5 and another control group treated with both PM2.5 at 12.8 mg/mL and artificial tears. On day 19, the whole eyes and meibomian glands were harvested for histopathological analyses and assessment of clinical scoring, tear volume, tear breakup time, and tear ferning. Furthermore, goblet cells by periodic acid Schiff stain and infiltrated eosinophils by Giemsa stain were quantified and compared among study groups. Results: Clinical scoring showed more eyelid edema, tearing, and scratching behaviors, with longer tear breakup time under the influence of increased PM2.5 concentrations. Tear ferning assay showed less tear crystal formation and decreased crystal branches after exposure to PM2.5. In addition, higher goblet cell density in the upper palpebral conjunctiva and extensive eosinophil infiltration in the entire conjunctiva and in the meibomian glands were induced by PM2.5. Conclusions: These results demonstrate that PM2.5 can induce symptoms similar to clinical allergic conjunctivitis and that the murine acute allergic conjunctivitis model can be induced by direct exposure to PM2.5.

Comparison of Renal Function and Other Predictors in Lacto-Ovo Vegetarians and Omnivores With Chronic Kidney Disease.

Objective Vegetarian diets have been shown to increase the risk of certain nutritional deficiencies, such as iron. As a number of patients with chronic kidney disease (CKD) in Taiwan are lacto-ovo vegetarians, the aim of this study was to investigate the effects of different proportions and sources of protein in lacto-ovo vegetarian and omnivorous diets, as well as the influence of adequate dietary protein intake, on renal function and nutritional status of Taiwanese patients with stage 3 to stage 5 CKD. Methods This is a cross-sectional study. In total, 100 outpatients with stage 3 to stage 5 CKD were enrolled in this study, including 40 lacto-ovo vegetarians and 60 omnivores. Subjects were divided into the lacto-ovo vegetarian group and omnivorous group based on dietary protein patterns. The indicators of renal function included estimated glomerular filtration rate (eGFR), creatinine, and blood urea nitrogen (BUN). Albumin, hemoglobin (Hb), and red blood cell count (RBC) measurements served as nutritional indicators. The levels of dietary energy and protein, as well as protein sources (plant or animal), were also analyzed. Results The levels of serum phosphate and triglycerides were significantly lower in the lacto-ovo vegetarian group than in the omnivore group, suggesting that lacto-ovo vegetarian diets have both phosphate-lowering and lipid-lowering effects, which could reduce the development of hyperphosphatemia and dyslipidemia. However, since all groups consumed higher than the recommended amounts of protein diet intake, no significant differences were observed in other renal function indices between the two groups. Conclusion Although a larger cohort study is necessary, the findings of this study could help patients with CKD to make healthier food choices and be used to support future medical nutritional therapies.

Effects of Reductants on Phytoextraction of Chromium (VI) by Ipomoea aquatica.

Reductants are often used to reduce Cr(VI) in chemical treatments, yet the effects of the reductants on Cr(VI) phytoremediation are not fully understood. This study investigates the effects of different reductants on Cr(VI) phytoremediation by Ipomoea aquatica in simulated solution with 3 mg L(-1) of Cr(VI), pH0 of 6, and an incubation time of 5 days. Results indicate that the applications of S2O3(2-), Fe0, and Fe2+ at low doses notably increased root Cr concentrations, which were obviously higher than that those in the control (Cr6+ alone). However, high reductant concentrations decreased bioaccumulation of Cr in the roots and shoots of the plant. Statistical results indicate that Cr concentrations were significantly and negatively correlated with Fe concentrations in the roots and shoots of the plant (p<0.05). This suggest that Fe accumulation inhibited Cr accumulation in the plant. A Cr(VI) concentration of 3 mg L(-1) caused short, brown lateral roots with tip necrosis, leaf chlorosis, and noticeable shoot wilting. The leaf necrosis and shoot wilting is caused by oxidative damage of lateral roots by Cr(VI) rather than by the reactive oxygen species generated by the oxidative stress. Addition of the reductants effectively reduced these plant injuries.

Dietary α-lipoic acid prevents UVB-induced corneal and conjunctival degeneration through multiple effects.

PURPOSE: This study investigated the effects of dietary α-lipoic acid (α-LA) against ultraviolet B (UVB)-induced corneal and conjunctival degeneration in a mouse model. METHODS: Female CBA mice were randomly divided into five study groups, including blank control, UVB without α-LA, and UVB with dietary α-LA at 1, 10, and 100 mg/kg body weight. Following UVB exposure, corneal surfaces were assessed along with immunohistochemistry for nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), malondialdehyde (MDA) accumulation, and P63⁺ basal cell distribution. Matrix metalloproteinase (MMP)-2 and MMP-9 activities were determined by gelatin zymography. ELISA assay was performed to confirm the findings of immunohistochemistry for NF-κB, COX-2, and MDA, along with the levels of TNF-α and IL-6. Tear production and goblet cell density were determined after tear strip assay and periodic acid Schiff staining, respectively. RESULTS: The results showed that UVB irradiation caused corneal surface damage, polymorphonuclear leukocyte infiltration, and loss of P63⁺ basal cells. Dietary α-LA ameliorated the UVB-induced corneal damage while simultaneously reducing MDA accumulation and maintaining P63⁺ basal cell survival. NF-κB-p65, COX-2, TNF-α, IL-6, and MMP-9 activity were all reduced by dietary α-LA. In addition, α-LA helped to reverse aqueous tear reduction, conjunctival squamous epithelium metaplasia, and goblet cell loss after UVB exposure. CONCLUSIONS: Dietary α-LA can prevent UVB-induced corneal damage and can be used as a prophylactic agent prior to excessive UVB exposure.

Assessment of ultraviolet B-blocking effects of weekly disposable contact lenses on corneal surface in a mouse model.

PURPOSE: Weekly disposable soft contact lenses have been widely used recently, but their shield effects against ultraviolet (UV) irradiation remain to be evaluated. This study investigated the bioprotective effects of several weekly soft contact lenses against UVB irradiation on the corneal surface in a mouse model. METHODS: Fifty ICR mice were randomly divided into five groups: (1) blank control, (2) exposed to UVB without contact lens protection, (3) exposed to UVB and protected with Vifilcon A contact lenses, (4) exposed to UVB and protected with Etafilcon A contact lenses, and (5) exposed to UVB and protected with HEMA+MA contact lenses. The exposure to UVB irradiation was performed at 0.72 J/cm²)/day after anesthesia for a 7-day period, followed by cornea surface assessment for smoothness, opacity, and grading of lissamine green staining. Tissue sections were prepared for hematoxylin and eosin staining and immunohistochemical detection by using antibodies against myeloperoxidase, cytokeratin-5, P63, Ki-67, nuclear factor-kappa B (p65), cyclooxygenase-2, Fas L, and Fas. RESULTS: The results showed impaired corneal surface with myeloperoxidase+ polymorphonuclear leukocyte infiltration into the stroma after UVB exposure, in contrast to the intact status of the blank controls. The corneas with Etafilcon A and HEMA+MA contact lenses maintained more cells positive for cytokeratin-5, P63, and Ki-67 compared to those with Vifilcon A or without contact lens protection. Furthermore, less proinflammatory factors, including nuclear factor-kappa (p65), cyclooxygenase-2, Fas L, and Fas, were induced in the corneas protected by Etafilcon A and HEMA+MA. CONCLUSIONS: This study demonstrated various protective effects of weekly disposable contact lenses against UVB irradiation. The mouse model used in the present study may be used extensively for in vivo assessment of UV shield efficacy.

Characterising visual deficits in children of an urban elementary school in Taiwan.

PURPOSE: The aim was to screen children from Grades 1 to 6 in an urban elementary school in Central Taiwan for visual deficits and associated parameters and, as an extension, to examine the acceptance of cycloplegic therapy as well as the lag in optimal vision correction. METHODS: Of 900 students in one school, 731 participated in the study, with parental consent. Data from 694 students, who had also completed a vision correction history were analysed. In addition to body height and weight, the screening included vision, non-cycloplegic autorefraction and distance retinoscopy, axial length and functional testing. RESULTS: There was a decrease in students with vision of 1.0 or better from 55.8 per cent in Grade 1 to 20.0 per cent in Grade 6. The decreases between Grades 2 and 3 and Grades 5 and 6 were significant. These trends were in general agreement with those based on refractive error and axial length. The students had abnormal functional findings including: stereoscopic vision, 9.2 per cent; cover tests, 14.1 per cent; pupillary responses, 13.8 per cent; and less commonly in extraocular muscular functions (3.0 per cent) and colour vision (5.2 per cent). A full 40 per cent of students received cycloplegic therapy with 25 per cent dropping out for various reasons. These cases were generally associated with lower vision and higher myopia. A lag between subnormal vision and optical correction was also observed with 55.1 per cent apparently not optimally corrected. Other parameters, including body height, weight and body mass index were not correlated with vision or refractive error. CONCLUSIONS: Age-dependent increase in the prevalence of myopia appears to continue despite the common practice of topical cycloplegic therapy in Taiwan. Timely correction of the refractive error is also lacking. While maintaining a visual acuity of 1.0 or better for all students at all times is not possible, this lag might be shortened by more frequent screening and/or direct provision of optical aids.

Macrophage migration inhibitory factor induces ICAM-1and thrombomobulin expression in vitro.

Macrophage migration inhibitory factor (MIF) is an important cytokine in the modulation of inflammatory and immune responses, but its role in coagulation remains to be elucidated. In this study, we investigated the potential role of MIF in coagulation through its influence on two factors, thrombomodulin (TM) and intercellular adhesion molecule-1 (ICAM-1). Recombinant human MIF was added to human microvascular endothelial cell line (HMEC-1) to investigate its influence on the expression of TM and ICAM-1. The results showed that both TM and ICAM-1 were induced with MIF addition in a dose-dependent and time-dependent manner. The expression of ICAM-1 and TM was increased as MIF doses were increased, with the highest expression seen at 12 hr after 400 ng/ml of MIF treatment. Besides, anti-MIF antibody treatment reduced the TM expression in HMEC-1 cells. In conclusion, our data support a role of MIF as an important factor in the regulation of coagulation.

Curcumin alleviates eosinophilic meningitis through reduction of eosinophil count following albendazole treatment against Angiostrongylus cantonensis in mice.

Angiostrongylus cantonensis (A. cantonensis) is the most common cause of parasitic eosinophilic meningitis worldwide. By using an animal model of BALB/c mice infected with A. cantonensis, previous studies indicated that the anthelmintic drug, albendazole, could kill A. cantonensis larvae and prevent further infection. However, the dead larvae will induce severe immune responses targeting at brain tissues. To alleviate the detrimental effects caused by the dead larvae, we administered curcumin, a traditional anti-inflammatory agent, as a complementary treatment in addition to albendazole therapy, to determine whether curcumin could be beneficial for treatment. The results showed that although curcumin treatment alone did not reduce worm number, combined treatment by albendazole and curcumin helped to reduce eosinophil count in the cerebrospinal fluid, better than using albendazole alone. This alleviating effect did not affect albendazole treatment alone, since histological analysis showed similar worm eradication with or without addition of curcumin. Nevertheless, curcumin treatment alone and combined albendazole-curcumin treatment did not inhibit MMP-9 expression in the brain tissue. In conclusion, curcumin, when used as a complementary treatment to albendazole, could help to alleviate eosinophilic meningitis through suppression of eosinophil count in the cerebrospinal fluid.