Cholesterol homeostasis regulated by ABCA1 is critical for retinal ganglion cell survival.

Genome-wide association studies have suggested a link between primary open-angle glaucoma and the function of ABCA1. ABCA1 is a key regulator of cholesterol efflux and the biogenesis of high-density lipoprotein (HDL) particles. Here, we showed that the POAG risk allele near ABCA1 attenuated ABCA1 expression in cultured cells. Consistently, POAG patients exhibited lower ABCA1 expression, reduced HDL, and higher cholesterol in white blood cells. Ablation of Abca1 in mice failed to form HDL, leading to elevated cholesterol levels in the retina. Counting retinal ganglion cells (RGCs) by using an artificial intelligence (AI) program revealed that Abca1-deficient mice progressively lost RGCs with age. Single-cell RNA sequencing (scRNA-seq) revealed aberrant oxidative phosphorylation in the Abca1-/- retina, as well as activation of the mTORC1 signaling pathway and suppression of autophagy. Treatment of Abca1-/- mice using atorvastatin reduced the cholesterol level in the retina, thereby improving metabolism and protecting RGCs from death. Collectively, we show that lower ABCA1 expression and lower HDL are risk factors for POAG. Accumulated cholesterol in the Abca1-/- retina causes profound aberrant metabolism, leading to a POAG-like phenotype that can be prevented by atorvastatin. Our findings establish statin use as a preventive treatment for POAG associated with lower ABCA1 expression.

Effects of Different Methods of Air Disinfection of Computed Tomography Rooms Dedicated to COVID-19 Cases.

OBJECTIVE: To monitor the number of bacterial colonies in the air of computed tomography (CT) room for COVID-19 using different disinfection methods and to identify the most effective method for disinfection and protection of equipment. METHODS: Three methods for disinfection using ultraviolet germicidal irradiation (group A), plasma circulation air sterilizer (group B), and ultraviolet germicidal irradiation plus plasma circulation air sterilizer (group C) were utilized to sanitize the air in the CT room dedicated to COVID-19 cases. Single-factor ANOVA was used to evaluate and compare the disinfection effect of the three air disinfection methods; an air microbial sampler was used to sample and measure the number of bacteria in the air of the machine room. RESULTS: The number of bacteria in the air immediately after disinfection was significantly lower than before disinfection (p < 0.01). All three disinfection methods met the disinfection requirement. No significant differences in the number of air bacteria in the machine room immediately after disinfection were observed among the three methods (p > 0.05). In addition, the effect of disinfection after 2 h was compared, and the number of bacteria in group C after 2 h was significantly lower than that in group A and group B. CONCLUSIONS: All three disinfection methods have significant disinfection effects. In addition, using ultraviolet disinfection lamps combined with a plasma air disinfection machine to sterilize the air in CT machine room has the best disinfection effect for the longest duration. Therefore, we recommend the combined disinfection method (ultraviolet disinfection lamps plus plasma air disinfection), as well as formulating relevant disinfection management norms, which should thus be the method to use during pandemics.

Problems and solutions of personal protective equipment doffing in COVID-19.

The progress of the coronavirus disease 2019 (COVID-19) pandemic is still severe. While everyone has been striving very hard to combat the pandemic, some healthcare professionals have shown varying degrees of infection symptoms and even died. The Chinese Army Medical Aid Team arrived in Wuhan on January 25, 2020, and quickly entered the battle against the pandemic after a short and rigorous training. As one of the earliest medical teams to enter the pandemic area, researchers have been exploring effective infection control measures that are currently in practice. Through observation and research, it has been noticed that layers of protective equipment have a hidden danger of infection while protecting the safety of the personnel. The members of each medical team have typically focused on the standard use of personal protective equipment (PPE). However, after a long period of intensive diagnosis and treatment in clinics and due to physical exertion and tiredness, problems such as improper operation are prone to occur during the tedious PPE doffing, thereby producing a relatively high risk of infection. This study primarily analyzes PPE doffing procedures, existing problems, and measures for improvement to explore methods to improve PPE donning and doffing and reduce the risk of infection.

Evaluation of the association between five genetic variants and primary open-angle glaucoma in a Han Chinese population.

PURPOSE: A large genome-wide association study showed that five new variants, {EPDR1 (rs3816415), CHAT (rs1258267), GLIS3 (rs736893), FERMT2 (rs7494379), and DPM2-FAM102A (rs3739821)}, were associated primary angle-closure glaucoma (PACG). Considering the shared clinical features between primary open-angle glaucoma (POAG) and PACG, this study was conducted to investigate the association of these genetic variants with POAG in a Han Chinese population. METHODS: A total 799 POAG patients and 799 controls are enrolled in this case-control study. All individuals were genotyped for the five single-nucleotide polymorphisms (SNPs) using ABI SNaPshot method. Four genetic models (homozygous, heterozygous, dominant, and recessive) were applied to further evaluate the possible correlation between the five SNPs and POAG. RESULTS: In our study, rs736893 in the GLIS3 gene was found to be associated with POAG (Bonferroni corrected p = .001, OR = 1.282, 95% CI = 1.103-1.491). Rs736893-AA and rs736893-AA/AG carriers showed an increase risk for POAG compared with rs736893-GG carriers (corrected p = .028, OR = 1.605, 95% CI = 1.137-2.267; corrected p = .012, OR = 1.349, 95% CI = 1.108-1.642; respectively) in homozygous and dominant models. For rs3816415 in the EPDR1 gene, rs3816415-AG and rs3816415-AA/AG carriers have a marginally lower risk than rs3816415-GG carriers (corrected p = .036, OR = 0.710, 95% CI = 0.548-0.919; corrected p = .04, OR = 0.718, 95% CI = 0.557-0.925) in heterozygous and dominant models. CONCLUSION: Our findings indicated that GLIS3 (rs736893) was associated with POAG in this Chinese population. Further genetic epidemiologic studies and functional work are necessary to reveal their pathogenesis with POAG.

Genome-wide analysis identified 17 new loci influencing intraocular pressure in Chinese population.

Intraocular pressure (IOP) is a major risk factor for glaucoma. Genetic determinants of intraocular pressure can provide critical insights into the genetic architecture of glaucoma and, as a result, open new avenues for therapeutic intervention. We performed a genome-wide association study and replication analysis of 8,552 Chinese participants. In the genome-wide association study, we identified 51 loci that surpassed the significance of P<9×10-7, and we formally replicated these loci. A combined discovery and replication meta-analysis identified 21 genome-wide loci that surpassed the genome-wide significance of P<5×10-8, including 4 previously reported loci: rs145063132 (7p21.2, ETV1/DGKB), rs548030386 (7q31.2, ST7 near CAV1/CAV2), rs7047871 (9p24.2, GLIS3), and rs2472494 (9q31.1, ABCA1/SLC44A1). Of the 17 newly identified loci, five were reported to have ocular related phenotypes: PTCH2 (rs7525308 in 1p34.1), LRIF1/DRAM2 (rs1282146 in 1p13.3), COLEC11 (rs201143466 in 2p25.3), SPTBN1 (rs4514918 in 2p16.2), and CRK (rs11078446 in 17p13.3). The genetic loci identified in this study not only increase our understanding of the genes involved in intraocular pressure but also provide important genetic markers to improve future genetic screening and drug discovery for intraocular pressure disorders.

Association of catalase polymorphisms with primary open-angle glaucoma in a Chinese population.

PURPOSE: Many genes have been associated with primary open-angle glaucoma (POAG). This study was conducted to investigate whether catalase (CAT) polymorphisms play a significant role in POAG in a Chinese population. METHODS: A cohort of 416 unrelated POAG patients and 997 unrelated control subjects was included in this case-control association study. CAT functional single-nucleotide polymorphisms (SNPs), including rs1001179, rs7943316, and rs769217, were genotyped by SNaPshot method. The genotype and allele frequencies were evaluated using the χ2 tests. The linkage disequilibrium (LD) and haplotype block structure association were examined using the program Haploview (Broad Institute, Cambridge, MA). RESULTS: There was a statistically significant difference for CAT functional SNP rs769217 between POAG cases and controls in the allelic model (p = 0.004, OR = 1.27, 95% CI 1.08-1.49). At this SNP, the allele frequency of the C allele in POAG cases was 0.587, which was higher than that in controls (0.528). However, no association was found for rs1001179 and rs7943316 with POAG. Pairwise LD analysis showed high LD between rs769217 and rs7943316 (D' = 0.857, r2 = 0.252, confidence bounds 0.71-0.93). After the association analysis for haplotype block structure generated from rs769217 with rs7943316, the data showed no significant association between the cases and controls. CONCLUSIONS: This study showed that CAT functional SNP rs769217 was significantly associated with POAG, implying that the CAT gene variants may play a role in the pathogenesis of POAG in the Chinese population.

Effects of dexamethasone and HA1077 on actin cytoskeleton and ß-catenin in cultured human trabecular meshwork cells.

AIM: To investigate the effects of dexamethasone (DEX) and 1-(5-isoquinolinesulfonyl)-homopiperazine (HA1077) on actin cytoskeleton and ß-catenin in cultured human trabecular meshwork (HTM) cells. METHODS: The HTM cells were separated from human eyeball and cultured in vitro. They were divided into control group, DEX (1×10-6 mol/L) group, HA1077 (3×10-5 mol/L) group, and DEX (1×10-6 mol/L) and HA1077 (3×10-5 mol/L) group. Actin cytoskeleton and ß-catenin in HTM cells of the four groups were examined by immunofluorescence and Western blot analyses. RESULTS: In DEX group, there were reorganization of actin cytoskeleton and formation of cross linked actin networks (CLANs), which were partially reversed in DEX and HA1077 group. DEX treatment also induced an increased expression of ß-catenin, which was obviously reduced in DEX and HA1077 group. Meanwhile, the cultured HTM cells in HA1077 group had lower expression of ß-catenin than that in the control group. CONCLUSION: Our results show that HA1077 can reverse the changes of actin organization and expression of ß-catenin induced by DEX in cultured HTM cells, suggesting that HA1077 may play an important role in increasing outflow and reducing intraocular pressure.

Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma.

We performed a genome-wide association study for primary open-angle glaucoma (POAG) in 1,007 cases with high-pressure glaucoma (HPG) and 1,009 controls from southern China. We observed genome-wide significant association at multiple SNPs near ABCA1 at 9q31.1 (rs2487032; P = 1.66 × 10(-8)) and suggestive evidence of association in PMM2 at 16p13.2 (rs3785176; P = 3.18 × 10(-6)). We replicated these findings in a set of 525 HPG cases and 912 controls from Singapore and a further set of 1,374 POAG cases and 4,053 controls from China. We observed genome-wide significant association with more than one SNP at the two loci (P = 2.79 × 10(-19) for rs2487032 representing ABCA1 and P = 5.77 × 10(-10) for rs3785176 representing PMM2). Both ABCA1 and PMM2 are expressed in the trabecular meshwork, optic nerve and other ocular tissues. In addition, ABCA1 is highly expressed in the ganglion cell layer of the retina, a finding consistent with it having a role in the development of glaucoma.