Personal exposure monitoring of fine and coarse particulate matter using exposure assessment models for elderly residents in Hong Kong.

This study investigated the determinants of personal exposures (PE) to coarse (PM2.5-10) and fine particulate matter (PM2.5) for elderly communities in Hong Kong. The mean PE PM2.5 and PM2.5-10 were 23.6 ± 10.8 and 13.5 ± 22.1 µg/m3, respectively during the sampling period. Approximately 76% of study subjects presented statistically significant differences between PE and ambient origin for PM2.5 compared to approximately 56% for PM2.5-10, possibly due to the coarse-size particles being more influenced by similar sources (road dust and construction dust emissions) compared to the PM2.5 particles. Individual PE to ambient (P/A) ratios for PM2.5 all exceeded unity (≥1), suggesting the dominant influences of non-ambient particles contributed towards total PE values. There were about 80% individual P/A ratios (≤1) for PM2.5-10, implying possible effective infiltration prevention of larger size particulate matter particles leading to dominant influences from the outdoor sources. The higher concentration of NO3- and SO42- in PM2.5-10 compared to PM2.5 suggests possible heterogeneous reactions of alkaline minerals leading to the formation of NO3- and SO42- in PM2.5-10 particles. The PE and ambient OC/EC ratios in PM2.5 (8.8 ± 3.3 and 10.4 ± 22.4, respectively) and in PM2.5-10 (6.0 ± 1.9 and 3.0 ± 1.1, respectively) suggest possible secondary formed OC from surrounding rural areas. Heterogeneous distributions (COD >0.2) between the PE and ambient concentrations were found for both the PM2.5 and PM2.5-10 samples. The calibration coefficient as the association between personal and surrogate exposure measure of PE to PM2.5 (0.84) was higher than PM2.5-10 (0.52). The findings further confirm that local sources were the dominant contributor to the coarse particles and these coefficients can potentially be used to estimate different PE to PM2.5 and PM2.5-10 conditions. A comprehensive understanding of the PE to determinants in coarse particles is essential to further reduce potential exposure misclassification.

Effects of long-term indoor air purification intervention on cardiovascular health in elderly: a parallel, double-blinded randomized controlled trial in Hong Kong.

Ambient fine particulate matter (PM2.5) is a leading environmental risk factor globally, and over half of the associated disease burden are caused by cardiovascular disease. Numerous randomized controlled trials (RCT) have investigated the short-term cardiovascular benefits of indoor air purifiers (IAPs), but major knowledge gaps remain on their longer-term benefits. In this 1-year, randomized, double-blinded, parallel controlled trial of 47 elderly (ntrue-purification = 24; nsham-purification = 23) aged ≥70 years, true-purification reduced household PM2.5 levels by 28% and maintained lower exposure throughout the year compared to the sham-purification group. After 12 months of intervention, a significant reduction of diastolic blood pressure was found in the true-purification versus sham-purification group (-4.62 [95% CI: -7.28, -1.96] mmHg) compared to baseline measurement prior to the intervention, whereas systolic blood pressure showed directionally consistent but statistically non-significant effect (-2.49 [95% CI: -9.25, 4.28] mmHg). Qualitatively similar patterns of associations were observed for pulse pressure (-2.30 [95% CI: -6.57, 1.96] mmHg) and carotid intima-media thickness (-10.0% [95% CI: -24.8%, 4.7%]), but these were not statistically significant. Overall, we found suggestive evidence of cardiovascular benefits of long-term IAPs use, particularly on diastolic blood pressure. Evidence on other longer-term cardiovascular traits is less clear. Further trials with larger sample sizes and long-term follow-up are needed across diverse populations to evaluate the cardiovascular benefits of IAPs.

Characteristics and sources of oxygenated VOCs in Hong Kong: Implications for ozone formation.

To investigate the characteristics of oxygenated volatile organic compounds (OVOCs) and their potential contribution to ozone (O3) generation, we conducted 3-h high-resolution observations during the summertime of 2022 and the wintertime of 2021. This study focused on a total of 28 OVOCs in five different chemical classes, which were encompassed at two representative sites in Hong Kong, including a roadside and an urban area. During the summertime, the total concentrations of quantified OVOCs (∑OVOCs) were 45 ± 12 and 63 ± 20 µg m-3 at the roadside and urban sites, respectively, whereas the ∑OVOCs decreased by 31 ± 11 % and 38 ± 13 %, respectively, during the wintertime. Among the classes of OVOCs, carbonyls and alcohols were the two predominant at both sites, with relatively higher concentration levels of acetone, methanol, butanaldehyde, and acrolein. The sources of OVOCs have significant spatial and temporal characteristics. Spatially, OVOCs were predominately attributed to primary emission and background at the roadside site, whereas they were a combination of primary emission, secondary formation, and background at the urban site. Temporally, background sources dominated the summertime OVOCs, while the contribution of primary emissions increased for the wintertime OVOCs. The O3 formation potential (OFP) for the OVOCs was calculated. The OFPs were 67 ± 16 and 119 ± 31 µg m-3 at the roadside and urban sites during the summertime, whereas the winter OFPs declined 30 % at the roadside and 38 % at the urban site. The background sources of carbonyls and alcohols at the roadside and of carbonyls and acrylates in the urban area were the major contributors to the summer OFP. Controlling the OVOC sources from local non-combustion sources such as gasoline-fuel evaporation and volatile chemical-containing products could lead to a reduction of OVOCs in the background and subsequently mitigate the OFP. This is beneficial for local O3 reduction in Hong Kong and surrounding regions.

Hong Kong-Macau Severe Hives and Angioedema Referral Pathway.

Background: Urticaria (defined as the presence of hives, angioedema, or both) can be caused by a variety of etiologies ranging from more common conditions such as chronic spontaneous urticaria (CSU) to rarer conditions such as hereditary angioedema (HAE). Specialist referral may be necessary in cases of severe urticaria or HAE, but access to specialist services remains limited in certain regions, such as the Greater Bay Area (GBA) of China. To address this, the Hong Kong-Macau Severe Hives and Angioedema Referral Pathway (SHARP) was initiated by the Hong Kong Institute of Allergy and Macau Society of Dermatology to promote multidisciplinary collaboration and regional exchange of expertise in the diagnosis and management of severe urticaria. Methods: A nominated task force of dermatologists and immunologists who manage patients with severe urticaria formulated the consensus statements (CS) using the Delphi method. The consensus was defined a priori as an agreement of ≥80%. Results: A total of 24 CS were formulated, including four statements on classifications and definitions, seven statements on diagnosis, and 13 statements on management and referral. The definitions for acute/chronic urticaria and severe CSU were stated. Unnecessary investigations and inappropriate medications were discouraged. The characteristics and recommended approach to suspected bradykinergic angioedema were specified. Stepwise treatment options using second-generation antihistamines, omalizumab, or cyclosporin for patients with CSU were addressed, and the importance of access to HAE-specific medications was emphasized. Furthermore, an integrated referral pathway for patients with severe hives and angioedema was constructed. Conclusion: The SHARP provides guidance for the management and specialist referral of patients with severe hives and angioedema in Hong Kong and Macau.

Inhibition of microRNA-328 Increases Ocular Mucin Expression and Conjunctival Goblet Cells.

We previously reported anti-miR-328 therapy for dry eye disease (DED). Since decreased mucin secretion is a risk factor for DED, we aimed to explore whether anti-miR-328 affects mucin expression and goblet cells. MiR-328 was increased in goblet cells when they were under desiccating stress or treated with benzalkonium chloride (BAC), both of which are risk factors for DED. Based on bioinformatics tool results, miR-328 was predicted to directly target the transcription factor CREB1 that has been known to promote the expression of mucin5AC. The inhibitory effect of miR-328 on CREB1 was confirmed by the transfection assay. A miR-328 binding site on the CREB1 gene was confirmed by the luciferase assay. Furthermore, anti-miR-328 increased CREB1 and mucin5AC in cultured goblet cells according to qPCR, Western blot, and IF staining experiments. Anti-miR-328 increased mucin5AC secretion from the cultured goblet cells based on an ELISA assay for the cultured medium. Finally, impression cytology data revealed anti-miR-328 increased conjunctival goblet cells in the DED rabbits induced by BAC. In conclusion, anti-miR-328 increases CREB1 expression leading to an increase in mucin5AC production and secretion. Furthermore, anti-miR-328 also increases conjunctival goblet cells. These results warrant the further development of anti-miR-328 therapy for DED.

miR-328-3p Affects Axial Length Via Multiple Routes and Anti-miR-328-3p Possesses a Potential to Control Myopia Progression.

Purpose: We previously reported miR-328-3p as a novel risk factor for myopia through a genetic association study of the PAX6 gene. In the present study, we first explored the effects of miR-328-3p on other myopia-related genes, and then tested whether anti-miR-328-3p may be used for myopia control. Methods: The luciferase report assay and transient transfection were used to confirm miR-328-3p target genes. The chromatin immunoprecipitation (ChIP) assay was used to investigate retinoic acid receptor on the miR-328-3p promoter. Mice and pigmented rabbits were induced to have myopia by the form deprivation method, and then anti-miR-328-3p oligonucleotide was topically instilled to the myopic eyes. The axial length was measured to assess the therapeutic effect of anti-miR-328-3p. A toxicity study using much higher doses was conducted to assess the safety and ocular irritation of anti-miR-328-3p. Results: The report assay and transfection of miR-328-3p mimic confirmed that miR-328-3p dose-dependently decreased both mRNA and protein expression of fibromodulin (FMOD) and collagen1A1 (COL1A1). We subsequently showed that FMOD promoted TGF-ß1 expression, and overexpression of FMOD increased the phosphorylation levels of p38-MAPK and JNK. The ChIP study showed that retinoic acid binds to miR-328-3p promoter and up-regulates miR-328-3p expression. In myopic animal studies, anti-miR-328-3p was as effective as 1% atropine and had a dose-dependent effect on suppressing axial elongation. In the toxicity study, anti-miR-328-3p did not cause any unwanted effects in the eyes or other organs. Conclusions: Micro (mi)R-328-3p affects myopia development via multiple routes. anti-miR-328-3p possesses a potential as a novel therapy for myopia control.

Fine particulate matter measured by satellites predicts the risk of age-related macular degeneration in a longitudinal cohort study.

Although studies have revealed that ambient particulate matter (PM) has detrimental effects on the ocular surface, there have been limited reports detailing the effect of ambient PM on the posterior segment of the eye. A large-scale longitudinal cohort study evaluating the association between fine PM, especially PM2.5, and the retina could elucidate the risk of ambient pollutants for retinal diseases. We investigated the association between PM2.5 and the development of age-related macular degeneration (AMD). We conducted a population-based cohort study of 4,284,128 participants in Taiwan between 2001 and 2011. PM2.5 was continuously measured by satellites and subsequently assigned to each geographic district along with its postcode. A time-dependent Cox proportional-hazard model was used to assess the overall effects of average PM2.5. We used distributed lag non-linear models to evaluate the dose-response relationship between PM2.5 and AMD development. The annual mean of PM2.5 exposure was 34.23 ± 7.17 µg/m3. The PM2.5 concentrations were highest in spring, followed by those in winter, autumn, and summer. Twelve thousand ninety-five new AMD cases were reported during the study period. After adjusting for covariates, the AMD risk increased by 19% (95% confidence interval 1.13-1.25) for a 10 µg/m3 PM2.5 increase. The present study demonstrated that chronic exposure to PM2.5 increases the risk of AMD. Almost half of the Taiwanese live in a polluted area where the PM2.5 levels are higher than the World Health Organization recommended air quality guideline of 10 µg/m3 had a 1.4-fold risk, which significantly increases concern about their visual health and social burden.

MicroRNA Therapy for Dry Eye Disease.

Purpose: We tested the role of microRNA-328 in dry eye disease (DED). Benzalkonium chloride (BAC) has been used to induce DED in animal models. We first demonstrated that both BAC and hyperosmotic stress induced overexpression of miR-328 in corneal cells and then tested whether anti-miR-328 could be a new therapy. Methods: BAC was instilled to both eyes of 41 rabbits and 19 mice from day 0 to 21 to induce DED. Animals of each species were divided to receive topical instillation of saline or anti-miR-328 eye drops between day 8 and 21. The DED signs were assessed by corneal fluorescein staining, histological examination, apoptosis of corneal cells, and inflammatory cytokines in rabbit eyes. For mice, only corneal fluorescein staining was assessed for the therapeutic effects. The corneal fluorescein staining scores ranged from 0 of no staining to 4 of coalescent. Results: For the rabbits, the staining score was significantly reduced (P = 0.038) after the 14-day anti-miR-328 treatment (n = 42 eyes), but the score was not improved by saline treatment (n = 40 eyes). Furthermore, rabbit eyes treated with anti-miR-328 had thicker corneal epithelium (P = 9.4 × 10-5), fewer apoptotic cells in corneal epithelium (P = 0.002), and stroma (P = 0.029) compared with the saline-treated eyes. Anti-miR-328 was more effective than saline to reduce the block of orifices of Meibomian glands, although such an effect was only marginally significant (P = 0.059). Similarly, anti-miR-328 was more effective than saline in reducing corneal staining in mouse eyes (P = 0.005). Conclusion: Overexpression of miR-328 may contribute to DED. Anti-miR-328 protects corneal cells and promotes re-epithelialization for DED treatment.

Collagen has a unique SEC24 preference for efficient export from the endoplasmic reticulum.

SEC24 is mainly involved in cargo sorting during COPII vesicle assembly. There are four SEC24 paralogs (A-D) in vertebrates, which are classified into two subgroups (SEC24A/B and SEC24C/D). Pathological mutations in SEC24D cause osteogenesis imperfecta with craniofacial dysplasia in humans. sec24d mutant fish also recapitulate the phenotypes. Consistent with the skeletal phenotypes, the secretion of collagen was severely defective in mutant fish, emphasizing the importance of SEC24D in collagen secretion. However, SEC24D patient-derived fibroblasts show only a mild secretion phenotype, suggesting tissue-specificity in the secretion process. Using Sec24d KO mice and cultured cells, we show that SEC24A and SEC24B also contribute to endoplasmic reticulum (ER) export of procollagen. In contrast, fibronectin 1 requires either SEC24C or SEC24D for ER export. On the basis of our results, we propose that procollagen interacts with multiple SEC24 paralogs for efficient export from the ER, and that this is the basis for tissue-specific phenotypes resulting from SEC24 paralog deficiency.

Craniofacial Diseases Caused by Defects in Intracellular Trafficking.

Cells use membrane-bound carriers to transport cargo molecules like membrane proteins and soluble proteins, to their destinations. Many signaling receptors and ligands are synthesized in the endoplasmic reticulum and are transported to their destinations through intracellular trafficking pathways. Some of the signaling molecules play a critical role in craniofacial morphogenesis. Not surprisingly, variants in the genes encoding intracellular trafficking machinery can cause craniofacial diseases. Despite the fundamental importance of the trafficking pathways in craniofacial morphogenesis, relatively less emphasis is placed on this topic, thus far. Here, we describe craniofacial diseases caused by lesions in the intracellular trafficking machinery and possible treatment strategies for such diseases.

Investigating factors influencing tourists' environmentally responsible behavior with extended theory of planned behavior for coastal tourism in Thailand.

Marine litter is one of the most significant marine environmental pollutants in coastal destinations around the world. Tourists' improper behavior in disposing of litter is a major contributor. The formation of tourists' environmentally responsible behavior (ERB) has thus become important in preventing and mitigating marine litter problems. This study aims to investigate factors affecting tourists' ERB using the extended theory of planned behavior (TPB). A questionnaire survey was conducted on Libong Island, Thailand between December 2019 and March 2020. A total of 876 respondents were surveyed. The empirical findings show that extended TPB with environmental awareness and environmental background can explain tourists' ERB. Recommendations for the formation of coastal tourists' ERB include (i) raising public awareness; (ii) promoting government administration; and (iii) elevating the quality of coastal attractions.

Robust hetero-MoO3/MoO2@N-doped carbon nanobelts decorated with oxygen deficiencies as high-performance anodes for potassium/sodium storage.

Hetero-MoO3/MoO2@N-doped carbon nanobelt anodes (h-MoO3/MoO2@NC) with long lifespan and superior rate capability were proposed by a simple in situ reduction tactic, in which pristine MoO3 was transformed into heterogeneous MoO3/MoO2. The hetero-MoO3/MoO2 architecture significantly improves the electronic conductivity and affords abundant oxygen deficiencies. Meanwhile, the synergistic effect of internal MoO3/MoO2 heterostructure and outer N-doped carbon layer (NC) accomplishes a balance of sustainable potassium/sodium storage and ultra-durable structure stability. In potassium ion batteries, the anodes steadily maintain a reversible capacity of 283 mAh g-1 after 6000 cycles at 0.5 A g-1 and 153 mAh g-1 after 1000 cycles under 2 A g-1, as well as an impressive rate capability of 131 mAh g-1 at 3 A g-1. In sodium ion batteries, the anodes purchase a steady capacity of 152 mAh g-1 even after 10,000 cycles at 2 A g-1, and 190 mAh g-1 after 5000 cycles at 0.5 A g-1. Moreover, the h-MoO3/MoO2@NC composite possesses a prominent pseudocapacitive effect and good thermal adaptability (-10 to 50 °C) in both KIBs and SIBs. The results indicate that the h-MoO3/MoO2@NC composite would be an auspicious material for potassium/sodium storage and other ion batteries.

PDE4B Proposed as a High Myopia Susceptibility Gene in Chinese Population.

Myopia is the most common cause of refractive error worldwide. High myopia is a severe type of myopia, which usually accompanies pathological changes in the fundus. To identify high myopia susceptibility genes, DNA-pooling based genome-wide association analysis was used to search for a correlation between single nucleotide polymorphisms and high myopia in a Han Chinese cohort (cases vs. controls in discovery stage: 507 vs. 294; replication stage 1: 991 vs. 1,025; replication stage 2: 1,021 vs. 52,708). Three variants (rs10889602T/G, rs2193015T/C, rs9676191A/C) were identified as being significantly associated with high myopia in the discovery, and replication stage. rs10889602T/G is located at the third intron of phosphodiesterase 4B (PDE4B), whose functional assays were performed by comparing the effects of rs10889602T/T deletion of this risk allele on PDE4B and COL1A1 gene and protein expression levels in the rs10889602T/Tdel/del, rs10889602T/Tdel/wt, and normal control A549 cell lines. The declines in the PDE4B and COL1A1 gene expression levels were larger in the rs10889602T/T deleted A549 cells than in the normal control A549 cells (one-way ANOVA, p < 0.001). The knockdown of PDE4B by siRNA in human scleral fibroblasts led to downregulation of COL1A1. This correspondence between the declines in rs10889602 of the PDE4B gene, PDE4B knockdown, and COL1A1 protein expression levels suggest that PDE4B may be a novel high myopia susceptibility gene, which regulates myopia progression through controlling scleral collagen I expression levels. More studies are needed to determine if there is a correlation between PDE4B and high myopia in other larger sample sized cohorts.

Real-Time Monitoring of the Effects of Personal Temperature Exposure on the Blood Oxygen Saturation Level in Elderly People with and without Chronic Obstructive Pulmonary Disease: A Panel Study in Hong Kong.

Few studies have investigated the short-term effect of personal temperature exposure on blood oxygen saturation (SpO2). We conducted this longitudinal panel study with real-time monitoring of SpO2 and environmental exposure for 3 continuous days for 20 patients with chronic obstructive pulmonary disease (COPD) and 20 healthy volunteers in Hong Kong, to explore the time course (from minutes to hours) of change in SpO2 in response to temperature in elderly people. We employed a generalized additive mixed model to evaluate the acute effects of personal temperature exposure on changes in SpO2 and risk of oxygen desaturation while adjusting for seasonality, environmental co-exposures, and personal characteristics. We observed a concurrent decline in SpO2 by 0.27% (95% confidence interval [CI]: 0.22-0.32%) and an increase in the risk of oxygen desaturation by an OR of 1.14 (95% CI, 1.10-1.18) associated with a 1 °C increase in personal temperature, and the association lasted over several hours. Results showed that the decline in SpO2 in elderly people was associated with an increase in personal temperature exposure within minutes to hours, particularly in women and male patients with COPD. Temperature-induced oxygen desaturation may play a pivotal role in COPD exacerbation.

Time course of blood oxygen saturation responding to short-term fine particulate matter among elderly healthy subjects and patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) often experience deteriorating gaseous exchange which in turn may result in declines in blood oxygen saturation (SpO2). Increasing evidence has also shown that elevated levels of fine particulate matter (PM2.5) may contribute to COPD pathogenesis. However, the acute effects of PM2.5 on SpO2 among COPD patients remain unclear, especially for its time course. Therefore, we conducted this panel study with 3-day real-time monitoring for personal PM2.5 exposure and concurrent SpO2 of 39 participants (20 COPD patients, 19 healthy participants), aged 60 to 90 years, in Hong Kong to explore the acute effects of personal PM2.5 exposure on SpO2 (within minutes to hours). We applied a linear mixed effect model to examine the associations between personal PM2.5 and SpO2, while adjusting for temporal trend, personal characteristics, weather conditions, and co-exposure to gaseous pollutants (ambient ozone, nitrogen dioxides, carbon monoxide, and atmospheric pressure). We found that short-term exposure to PM2.5 might result in acute declines of SpO2 within minutes, and the effects would last for several hours. An interquartile range increase of personal PM2.5 exposure (17.2 µg/m3) was associated with -0.19% (95% CI: -0.26% to -0.12%) changes of concurrent SpO2 for all participants. The most significant decline was observed at lag0-3 h, and then became insignificant at lag0-12 h. At lag0-1 h, estimated mean changes of SpO2 were -0.40% (95% CI: -0.55% to -0.24%) for COPD patients and -0.09% (95% CI: -0.23% to 0.06%) for healthy participants. Compared with healthy participants, the effects of PM2.5 exposure on SpO2 for COPD patients were slightly stronger and more acute. Reducing PM2.5 concentrations might be a useful approach to improve health status and reduce exacerbations for COPD patients.

Consequences of mutations in the genes of the ER export machinery COPII in vertebrates.

Coat protein complex II (COPII) plays an essential role in the export of cargo molecules such as secretory proteins, membrane proteins, and lipids from the endoplasmic reticulum (ER). In yeast, the COPII machinery is critical for cell viability as most COPII knockout mutants fail to survive. In mice and fish, homozygous knockout mutants of most COPII genes are embryonic lethal, reflecting the essentiality of the COPII machinery in the early stages of vertebrate development. In humans, COPII mutations, which are often hypomorphic, cause diseases having distinct clinical features. This is interesting as the fundamental cellular defect of these diseases, that is, failure of ER export, is similar. Analyses of humans and animals carrying COPII mutations have revealed clues to why a similar ER export defect can cause such different diseases. Previous reviews have focused mainly on the deficit of secretory or membrane proteins in the final destinations because of an ER export block. In this review, we also underscore the other consequence of the ER export block, namely ER stress triggered by the accumulation of cargo proteins in the ER.

Platinum-based combination chemotherapy triggers cancer cell death through induction of BNIP3 and ROS, but not autophagy.

These days, cancer can still not be effectively cured because cancer cells readily develop resistance to anticancer drugs. Therefore, an effective combination of drugs with different mechanisms to prevent drug resistance has become a very important issue. Furthermore, the BH3-only protein BNIP3 is involved in both apoptotic and autophagic cell death. In this study, lung cancer cells were treated with a chemotherapy drug alone or in combination to identify the role of BNIP3 and autophagy in combination chemotherapy for treating cancer. Our data revealed that various combinational treatments of two drugs could increase cancer cell death and cisplatin in combination with rapamycin or LBH589, which triggered the cell cycle arrest at the S phase. Cells with autophagosome and pEGFP-LC3 puncta increased when treated with drugs. To confirm the role of autophagy, cancer cells were pre-treated with the autophagy inhibitor 3-methyladenine (3-MA). 3-MA sensitized cancer cells to chemotherapy drug treatments. These results suggest that autophagy may be responsible for cell survival in combination chemotherapy for lung cancer. Moreover, BNIP3 was induced and localized in mitochondria when cells were treated with drugs. The transfection of a dominant negative transmembrane deletion construct of BNIP3 (BNIP3ΔTM) and treatment of a reactive oxygen species (ROS) inhibitor suppressed chemo drug-induced cell death. These results indicate that BNIP3 and ROS may be involved in combination chemo drug-induced cell death. However, chemo drug-induced autophagy may protect cancer cells from drug cytotoxicity. As a result, inhibiting autophagy may improve the effects of combination chemotherapy when treating lung cancer.

Traffic-related air pollutants increase the risk for age-related macular degeneration.

The aim of this study was to investigate whether ambient nitrogen dioxide (NO2) and carbon monoxide (CO) increase the risk for age-related macular degeneration (AMD). This is a longitudinal population-based study using the data on Taiwan National Health Insurance Program between year 2000 and 2010. From the nationwide dataset, we enrolled subjects aged 50 or older and the annually total NO2 and CO exposure was calculated from 1998 to 2010 for each subject. The Cox proportional hazard regression was used to estimate the HRs with adjustment for other variables. A total of 39,819 AMD-free residents were enrolled, and 1442 participants developed AMD during the 11 -year follow-up. Compared with the lowest exposure quartile, the highest quartile of each air pollutant was associated with an increased risk for AMD. The adjusted HR was 1.91 (95% CI 1.64 to 2.23, p<0.001) for the highest NO2 quartile, and was 1.84 (95% CI 1.5 to 2.15, p<0.001) for the highest CO quartile. In this study, chronic exposure to the highest quartile of ambient NO2 or CO significantly increases the risk for AMD.

HOXA9 is a novel myopia risk gene.

PURPOSE: A recent meta-analysis revealed PAX6 as a risk gene for myopia. There is a link between PAX6 and HOXA9. Furthermore, HOXA9 has been reported to activate TGF-ß that is a risk factor for myopia. We speculate HOXA9 may participate in myopia development. METHODS: The Singapore GUSTO birth cohort provides data on children's cycloplegic refraction measured at age of 3 years and their methylation profile based on the umbilical cord DNA. The HOXA9 expression levels were measured in the eyes of mono-ocular form deprivation myopia in mice. The plasmid with the mouse HOXA9 cDNA was constructed and then transfected to mouse primary retinal pigment epithelial (RPE) cells. The expression levels of myopia-related genes and cell proliferation were measured in the HOXA9-overexpressed RPE cells. RESULTS: A total of 519 children had data on methylation profile and cycloplegic refraction. The mean spherical equivalent refraction (SE) was 0.90D. Among 8 SE outliers (worse than -2D), 7 children had HOXA9 hypomethylation. The HOXA9 levels in the retina of myopic eyes was 2.65-fold (p = 0.029; paired t-test) higher than the uncovered fellow eyes. When HOXA9 was over-expressed in the RPE cells, TGF-ß, MMP2, FGF2 and IGF1R expression levels were dose-dependently increased by HOXA9. However, over-expression of HOXA9 had no significant influence on IGF1 or HGF expression. In addition, HOXA9 also increased RPE proliferation. CONCLUSION: Based on the human, animal and cellular data, the transcription factor HOXA9 may promote the expression of pro-myopia genes and RPE proliferation, which eventually contribute to myopia development.