Integrated metabolomics and transcriptomic analysis reveals metabolic changes of flavor compounds of Camellia assamica host plant after parasitized by Viscumarticulatum.

Tea is one of the most popular beverages, it has many health benefits and flavor properties due to the presence of numerous secondary metabolites. Camellia assamica is also a main source of tea, which is mainly planted in the regions of southwest China. In this study, a non-targeted and targeted metabolomics analysis and sensory evaluation on tea leaves with and without mistletoe (Viscum articulatum) was carried out using liquid chromatography-mass spectrometry. RNA-seq-based transcriptomic analysis was conducted in parallel on the same samples, subsequently gene expression and metabolic differentiation were also investigated. Tea leaves with mistletoe presented much lower contents of (-)-catechin, (-)-epicatechin, (-)-gallocatechin gallate and (-)-epicatechin gallate, but significantly higher levels of free amino acids including Arg, Asp, GABA and Gln than that without mistletoe. Transcriptomic analysis also confirmed the main differentially expressed genes (DEGs) containing phenylpropanoid and flavonoid biosynthesis were down-regulated, but genes of amino acid biosynthesis were up-regulated. qRT-PCR analysis further revealed that the relative expression of CsCHS, CsC4H, CsANS, CsLAR, and CsF3H was hindered, while CsglyA and CsilvE expression was increased.

CsRVE1 promotes seasonal greening of albino Camellia sinensis cv. Huangkui by activating chlorophyll biosynthesis.

Seasonal greening is a crucial survival strategy for albino tea cultivars, during which dysfunctional chloroplasts recover and chlorophyll biosynthesis increases in albino leaves. However, the regulatory mechanisms of seasonal greening in albino tea plants remain unclear. Here, we report that CsRVE1, a nuclear-located Myb-like transcription factor, can positively modulate the seasonal greening of albino Camellia sinensis cv. Huangkui leaves by activating the expression of genes involved in light harvesting and chlorophyll biosynthesis. The transcriptional expression of CsRVE1 increased during seasonal greening and was tightly correlated with increases in the expression of genes involved in light harvesting (CsLhcb) and chlorophyll biosynthesis (CsCHLH, CsHEMA1 and CsCAO). In vivo and in vitro molecular analyses showed that CsRVE1 can directly bind to the promoters of CsLhcb, CsCHLH and CsPORA, eventually leading to chlorophyll accumulation in tea leaves. Furthermore, transient suppression of CsRVE1 in tea leaves led to a decrease in target gene expression. In contrast, the overexpression of CsRVE1 in Arabidopsis led to chlorophyll increases and the activation of AtLhcb, AtPORA, AtCHLH, etc. These results identify CsRVE1 as an important promoter of seasonal greening that functions by regulating genes involved in chlorophyll biosynthesis in albino tea plants and shed new light on the regulatory mechanisms of leaf phenotypes in plants.

[Characteristics of Soil Carbon, Nitrogen, Phosphorus, and Ecological Stoichiometry in Vegetable Fields and Orchard in the Coastal Area of Fuzhou].

The soil ecological stoichiometric characteristics of different agricultural land use types have a certain indicator function for characterizing the level of soil nutrient supply and are of great significance to the management of nutrient resources in farmland ecosystems. In order to reveal the soil carbon (C), nitrogen (N), and phosphorus (P) contents and their ecological stoichiometric characteristics in different vegetable fields and orchard agricultural land use types, this study took vegetable fields (taro field and jicama field) and orchards (citrus tree orchard, watermelon field, and pear tree orchard) as the research objects in the coastal area of Fuzhou City. The contents of soil C, N, and P and their ecological stoichiometric characteristics in different vegetable fields and orchard agricultural land uses were measured and analyzed. The soil C and N contents were in the order of orchard>vegetable field (P<0.05). The C content in the citrus tree orchard was the highest (4.44 g·kg-1), and the N content in the watermelon field was the highest (1.46 g·kg-1). The soil P content was vegetable field>orchard (P<0.05), and the jicama field had the highest P content (0.19 g·kg-1). The soil carbon and nitrogen ratio (C/N), carbon and phosphorus ratio (C/P), and nitrogen and phosphorus ratio (N/P) were orchard>vegetable field (P<0.05). Among them, the citrus tree orchard had the highest C/N (7.40) and C/P (61.43), and the watermelon field had the highest N/P (10.27). Soil N content was significantly and negatively correlated with bulk density and conductivity (r=-0.49, r=-0.28, P<0.05), and there was a significant and positive correlation with soil water content (r=0.61, P<0.05). C/P and C/N were significantly and positively correlated with SOM (r=0.71, r=0.64, P<0.01). In the process of crop planting and management in the coastal area of Fuzhou City, it is necessary to reasonably add nitrogen fertilizer to compensate for the N limitation, and slow-release nitrogen fertilizer is better for promoting the sustainable supply of nitrogen nutrients in the growth and development of crops.

UV-B regulates seasonal greening of albino leaves by modulating CsHY5-inhibiting chlorophyll biosynthesis in Camellia sinensis cv. Huangkui.

Seasonal greening is crucial for albino plants but the underlying regulatory mechanism is unclear, especially concerning light regulation as one of the most important environmental factors for light-sensitive albino tea plants. Here, we report that the UV-B signal regulates the seasonal greening process of albino leaves by modulating CsHY5-inhibiting chlorophyll biosynthesis in Camellia sinensis cv. Huangkui. Reduction of solar UV-B in plantation promoted the seasonal greening of albino 'HK' leaves by inhibiting CsHY5 transcription and activating genes involved in light-harvesting CsLhlb and the chlorophyll biosynthetic pathway (CsCHLH, CsHEMA1, and CsPORA), leading to enrichment of chlorophyll accumulation and recovery of dysfunctional chloroplasts. In contrast, indoor supplementary UV-B exposure reduced chlorophylls by activating CsHY5 but inhibiting chlorophyll biosynthetic genes. In vivo and in vitro molecular analyses showed that CsHY5 can directly bind to the promoters of CsLhlb, CsCHLH, CsHEMA1, and CsPORA. These results indicate that CsHY5 acts as a repressor for the seasonal greening of the albino tea plants in response to the UV-B signal. This is the first study that investigates the regulatory role of the CsHY5-mediated UV-B signal in regulating the seasonal greening of the albino tea plant, which improves our understanding of light regulation in leaf phenotypes of higher plants.

Effects of nitrogen-enriched biochar on subtropical paddy soil organic carbon pool dynamics.

Agronomic management practices present an opportunity to improve the sustainability of crop production, including reductions of greenhouse gas emissions through impacts on soil organic carbon (SOC) dynamics. We investigated the impacts of contrasting application rates of nitrogen (N)-enriched biochar (4 and 8 t ha-1) on the concentrations of total and active SOC, microbial biomass carbon (MBC), soil aggregates, and the carbon (C) pool management index (CPMI) as an indicator of soil quality in tillering and mature subtropical early and late rice in China. Soil salinity and soil bulk density increased, and soil water content generally decreased under the application of N-enriched biochar at 4 t ha-1. Following the application of the biochar, there were greater soil concentrations of SOC and lower concentrations of dissolved organic-C and active labile organic­carbon, indicating reduced mineralization and enhanced stocks of stable-C. Biochar application (4 and 8 t ha-1) led to lower soil Ca-SOC concentrations and greater soil Fe(Al)-SOC concentrations. Concentrations of Fe(Al)-SOC were greater under the application of N-enriched biochar at 4 t ha-1, indicating the bonding capacity of iron­aluminum oxide and organic carbon provided by biochar improved levels of SOC fixation. The composition of soil aggregates under each treatment was mainly micro-aggregates (<0.25 mm). The greater soil content of macro-aggregates (>0.25 mm) increased under amendment with 4 t of biochar ha -1 and the greater SOC content led to greater soil aggregate stability. Levels of C pool activity, C pool index, and CPMI reduced following application of the biochar, while C pool activity index increased slightly, indicating an increase in soil quality. These results indicate that the application of N-enriched biochar during rice cultivation may lead to reductions in SOC mineralization and C emissions and increases in soil C sink capacity, due to greater SOC pool stability, thus improving the sustainability of paddy rice production.

Transcriptome analysis in contrasting maize inbred lines and functional analysis of five maize NAC genes under drought stress treatment.

Drought substantially influences crop growth and development. NAC (NAM, ATAF1/2, and CUC2) transcription factors (TFs) have received much attention for their critical roles in drought stress responses. To explore the maize NAC genes in response to drought stress, the transcriptome sequencing data of NAC TFs in two maize inbred lines, the drought tolerance line H082183 and the sensitive line Lv28, were used to screen the differentially expressed genes (DEGs). There were 129 maize NAC protein-coding genes identified, of which 15 and 20 NAC genes were differentially expressed between the two genotypes under MD and SD treatments, respectively. Meanwhile, the phylogenetic relationship of 152 non-redundant NAC family TFs in maize was generated. The maize NAC family proteins were grouped into 13 distinct subfamilies. Five drought stress-responsive NAC family members, which were designed as ZmNAP, ZmNAC19, ZmNAC4, ZmJUB1(JUBGBRUNNEN1), and ZmNAC87, were selected for further study. The expression of ZmNAP, ZmNAC19, ZmNAC4, ZmJUB1, and ZmNAC87 were significantly induced by drought, dehydration, polyethylene glycol (PEG) stress, and abscisic acid (ABA) treatments. The overexpressing Arabidopsis of these five NAC genes was generated for functional characterization, respectively. Under different concentrations of NaCl, D-mannitol stress, and ABA treatments, the sensitivity of ZmNAP-, ZmNAC19-, ZmNAC4-, ZmJUB1-, and ZmNAC87-overexpressing lines was significantly increased at the germination stage compared to the wild-type lines. The overexpression of these five NAC members significantly improved the drought stress tolerance in transgenic Arabidopsis. Yeast two-hybrid screening analysis revealed that ZmNAP may cooperatively interact with 11 proteins including ZmNAC19 to activate the drought stress response. The above results inferred that ZmNAP, ZmNAC19, ZmNAC4, ZmJUB1, and ZmNAC87 may play important roles in the plant response to drought stress and may be useful in bioengineering breeding and drought tolerance improvement.

Vitamin D supplementation induces CatG-mediated CD4+ T cell inactivation and restores pancreatic ß-cell function in mice with type 1 diabetes.

Type 1 diabetes (T1D) is a chronic autoimmune disease accompanied by the immune-mediated destruction of pancreatic ß-cells. In this study, we aimed to explore the regulatory effects of vitamin D (VD) supplementation on pancreatic ß-cell function by altering the expression of bioinformatically identified cathepsin G (CatG) in T1D mice. A T1D mouse model was established in nonobese diabetic (NOD) mice, and their islets were isolated and purified. Pancreatic mononuclear cells (MNCs) were collected, from which CD4+ T cells were isolated. The levels of interleukin (IL)-2, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the supernatant of mouse pancreatic tissue homogenate were assessed using ELISA. Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelin (TUNEL) staining were conducted to evaluate the effects of VD supplementation on pancreatic tissues of T1D mice. The pancreatic ß-cell line MIN6 was used for in vitro substantiation of findings in vivo. VD supplementation reduced glucose levels and improved glucose tolerance in T1D mice. Furthermore, VD supplementation improved pancreatic ß-cell function and suppressed immunological and inflammatory reactions in the T1D mice. We documented overexpression of CatG in diabetes tissue samples, and then showed that VD supplementation normalized the islet immune microenvironment through downregulating CatG expression in T1D mice. Experiments in vitro subsequently demonstrated that VD supplementation impeded CD4+ T activation by downregulating CatG expression and thereby enhanced pancreatic ß-cell function. Results of the present study elucidated that VD supplementation can downregulate the expression of CatG and inhibit CD4+ T cell activation, thereby improving ß-cell function in T1D.NEW & NOTEWORTHY We report that vitamin D (VD) supplementation downregulates CatG expression and inhibits CD4+ T cell activation, thereby improving ß-cell function in type 1 diabetes (T1D). This study deepens our understanding of the pathogenesis of T1D and clarifies molecular events underlying the alleviatory effect of VD for immunotherapy against T1D.

Ambient Ultraviolet B Signal Modulates Tea Flavor Characteristics via Shifting a Metabolic Flux in Flavonoid Biosynthesis.

Tea leaves contain an extraordinarily high level of flavonoids that contribute to tea health benefits and flavor characteristics, but the regulatory mechanism of ambient ultraviolet B (UV-B) on tea flavonoid enrichment remains unclear. Here, we report that ambient UV-B modulates tea quality by inducing a metabolic flux in flavonoid biosynthesis. UV-B absence decreased bitter- and astringent-tasting flavonol glycosides (kaempferol-7-O-glucoside, myricetin-3-O-glucoside, and quercetin-7-O-glucoside) but increased non-galloylated catechins. Conversely, supplementary UV-B increased flavonols and decreased catechins in tea leaves. These responses were achieved via CsHY5, which mediates the UV-B-induced MYB12 activation and binds to the promoters of flavonoid biosynthetic genes (CsFLS, CsLARa, and CsDFRa), leading to flavonoid changes. Transcriptomic data indicated that UV-B-induced tea flavonoid regulation is responsive to multiple biotic and abiotic environmental stresses. These findings improve our understanding of light-regulated tea astringency and bitterness underlying shading effects and seasonal light changes and provide novel insights into tea cultivation management and processing.

Lentiviral vector-mediated expression of C3 transferase attenuates retinal ischemia and reperfusion injury in rats.

AIMS: Our previous study showed that intravitreal delivery of self-complementary AAV2 (scAAV2)-mediated exoenzyme C3 transferase (C3) can attenuate retinal ischemia/reperfusion (I/R) injury. The current study investigated the neuroprotective effects of lentivirus (LV)-mediated C3 transgene expression on rat retinal I/R injury. MAIN METHODS: The LV encoding C3 and green fluorescent protein (GFP) together (LV-C3-GFP) or GFP only (LV-GFP) was intravitreally injected to SPRAGUE-DAWLEY rats. On day 5 post-intravitreal injection, eyes were evaluated by slit-lamp examination. The GFP expression on retina was confirmed by in vivo and ex vivo assessments. RhoA GTPase expression in retina was examined by western blot. Retinal I/R injury was generated by transiently increasing intraocular pressure (110 mmHg, 90 min). Eyes were then enucleated, and retinas processed for morphological analysis and TdT-dUTP terminal nick-end labeling (TUNEL) assay. KEY FINDINGS: No obvious inflammatory reactions or surgical complications were observed after intravitreal injection of LV vectors. There was a significant decrease of total RhoA GTPase level in the retina treated with LV-C3-GFP. Compared to the blank control group, LV-C3-GFP and LV-GFP did not affect the retinal thickness, cell density in ganglion cell layer (GCL), or numbers of apoptotic cells in retinal flat-mounts. In the LV-GFP-treated retinas, I/R decreased the retinal thickness and GCL cell density and increased apoptotic retinal cell numbers. LV-C3-GFP significantly protected against all these degenerative effects of I/R. SIGNIFICANCE: This study indicated that LV-mediated C3 transgene expression exhibits neuroprotective effects on the retinal I/R injury and holds potential as a novel neuroprotective approach targeting certain retinopathies.

The role of non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A PRISMA-compliant article.

BACKGROUND: Given the huge burden of atrial fibrillation (AF) and AF-related stroke in Asia, stroke prevention represents an urgent issue in this region. We herein performed a network meta-analysis to examine the role of non-vitamin K antagonist oral anticoagulants (NOACs) in Asian patients with AF. METHODS: A systematic search of the publications was conducted in PubMed and Embase databases for eligible studies until July 2019. The odds ratios (ORs) and 95% confidence intervals (CIs) were regarded as the effect estimates. The surface under the cumulative ranking area (SUCRA) for the ranking probabilities was calculated. RESULTS: A total of 17 studies were included. For comparisons of NOACs vs warfarin, dabigatran (OR = 0.77, 95% CI 0.68-0.86), rivaroxaban (OR = 0.72, 95% CI 0.65-0.81), apixaban (OR = 0.56, 95% CI 0.49-0.65), but not edoxaban reduced the risk of stroke or systemic embolism, wheres dabigatran (OR = 0.56, 95% CI 0.41-0.76), rivaroxaban (OR = 0.66, 95% CI 0.50-0.86), apixaban (OR = 0.49, 95% CI 0.36-0.66), and edoxaban (OR = 0.34, 95% CI 0.24-0.49) decreased the risk of major bleeding. In reducing the risk of stroke or systemic embolism, apixaban and rivaroxaban ranked the best and second best (SUCRA 0.2% and 31.4%, respectively), followed by dabigatran (50.2%), edoxaban (75.2%), and warfarin (93.0%). In reducing the risk of major bleeding, edoxaban, and apixaban ranked the best and second best (1.5% and 30.8%, respectively), followed by dabigatran (48.4%), rivaroxaban (69.2%), and warfarin (100%). CONCLUSION: NOACs were at least as effective as warfarin, but more safer in Asians with AF. Apixaban was superior to other NOACs for reducing stroke or systemic embolism, while edoxaban showed a better safety profile than other NOACs.

Author Correction: Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2Y1 and P2Y12 receptors.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2Y1 and P2Y12 receptors.

Many hemorheologic Traditional Chinese Medicines (TCMs) that are widely-used clinically lack molecular mechanisms of action. We hypothesized that some of the active components of hemorheologic TCMs may function through targeting prothrombotic P2Y1 and/or P2Y12 receptors. The interactions between 253 antithrombotic compounds from TCM and these two G protein-coupled P2Y receptors were evaluated using virtual screening. Eleven highly ranked hits were further tested in radioligand binding and functional assays. Among these compounds, salvianolic acid A and C antagonized the activity of both P2Y1 and P2Y12 receptors in the low µM range, while salvianolic acid B antagonized the P2Y12 receptor. These three salvianolic acids are the major active components of the broadly-used hemorheologic TCM Danshen (Salvia militorrhiza), the antithrombotic molecular mechanisms of which were largely unknown. Thus, the combination of virtual screening and experimental validation identified potential mechanisms of action of multicomponent drugs that are already employed clinically.

Evaluation of the photooxidation efficiency of As(III) applying the UVC/oxalate technique.

In this study, the photooxidation capacity of UVC/Oxalate (Ox) was evaluated using As(III) as a typical pollutant. The results show that the direct oxidation amount of As(III) induced by UVC in water was negligible, but the presence of Ox remarkably accelerated the oxidation rate of As(III). Under UVC irradiation, 50 µM As(III) can be completely oxidized to As(V) in the case of Ox concentration above 300 µM within 60 min. As(III) oxidation was found greatly related with the photodecomposition of Ox. Much more Ox can be mineralized in more acidic solution. At the same time, the photooxidation of As(III) was significantly favored at decreased initial pH from 8.0 to 3.0. In this reaction system, the role of oxygen was indispensable for Ox photodecomposition and As(III) photooxidation, which can be ascribed to its special roles as a precursor of reactive superoxide and an electron acceptor. In oxygen-present atmosphere, the in situ production of H2O2 was detected during the photolysis of Ox and its photolysis product, i.e., OH primarily contributed to the oxidation of As(III). However, the photodecomposition of Ox and photooxidation of As(III) were significantly inhibited in the anaerobic environment. In general, the homogeneous photolysis of Ox in many commonly practiced UVC oxidation processes can be also proposed as a supplementary method of generating highly oxiditive species in aerobic condition.

Antiviral Activity of a Cloned Peptide RC28 Isolated from the Higher Basidiomycetes Mushroom Rozites caperata in a Mouse Model of HSV-1 Keratitis.

An Escherichia coli-expressed peptide with a molecular weight of 28.26, derived from the complementary DNA of antiviral protein RC28 isolated from the mushroom Rozites caperata (=Cortinarius caperatus), demonstrated potent antiviral activity against herpes simplex virus-1 in Vero cells and in a herpes simplex virus-1 mouse keratitis model. Plaque assays in Vero cells showed that the peptide reduced viral yields by at least 1.2 logs; in the animal model the cloned peptide delayed the occurrence of stromal keratitis and alleviated the severity of the disease. We believe this is the first report of a cloned mushroom peptide with antiviral activity for the prevention and treatment of a viral disease.

Implication of ICP0 translocation and peroxisome functions in the inhibition of HSV-1 by the antiviral protein RC28 from the higher Basidiomycetes mushroom Rozites caperata.

RC28 an antiviral protein of MW 28.25 kD isolated from the edible mushroom Rozites caperata (RC) (=Cortinarius caperatus), was tested for its ability to block HSV-1 functions. The protein blocked the translocation of the immediate early protein ICP0 from the nucleus to the cytoplasm. Target studies using an array of yeast proteins revealed that the protein binds preferentially to some yeast peroxisome proteins. An antagonist of the peroxisome proliferator nuclear receptor complex (PPAR) [2-chloro-5-nitro-(N-pyridyl) benzamide (MW 277.7)] was inhibitory to both HSV-1 and HSV-2 at EC50 values of 5.8 and 10 µM, respectively. Prevention of the cytoplasmic functions of ICP0 and perturbations of peroxisomal metabolism utilized by HSV-1 are likely antiviral targets of the mushroom protein.

Haloemodin as novel antibacterial agent inhibiting DNA gyrase and bacterial topoisomerase I.

Drug-resistant bacterial infections and lack of available antibacterial agents in clinical practice are becoming serious risks to public health. We synthesized a new class of haloemodins by modifying a traditional Chinese medicine component, emodin. The novel haloemodin exerts strong inhibitory activity on bacterial topoisomerase I and DNA gyrase, and not on the topoisomerases of human origin. In principle, it shows remarkable antibacterial activities against laboratory and clinically isolated Gram-positive bacteria, including vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus. We further expanded its antibacterial spectrum into against Gram-negative bacteria with the assistance of polymyxin B nonapeptide, which helps haloemodin to penetrate through the bacterial outer membrane. Finally, the therapeutic effect of haloemodin in vivo was confirmed in curing S. aureus-induced keratitis on rabbit model. With distinctive structural difference from the antibiotics we used, the haloemodins are of value as promising antibacterial pharmacophore, especially for combat the infections caused by drug-resistant pathogens.

Release of phosphorous impurity from TiO2 anatase and rutile nanoparticles in aquatic environments and its implications.

Phosphorus-bearing materials as an additive have been popularly used in nanomaterial synthesis and the residual phosphorus within the nanoparticles (NPs) can be of an environmental concern. For instance, phosphorus within pristine commercial TiO2 NPs greatly influences the surface charge and aggregation behavior of the host TiO2 in aquatic environments; however, it is unknown whether and how fast phosphorus is released. In this study, we focus on the phosphorus release kinetics from five types of TiO2 NPs (i.e., 5, 10, and 50 nm anatase and 10 × 40, 30 × 40 nm rutile) under the influence of varying solution chemistries. The 50 nm anatase has the highest quantity of P (8.05 g/kg) and most leachable P dissolves within the first 2 h (i.e., 5.01 g/kg), which presents a potential pollutant source of P. Higher pH favors the phosphorus release (release order: pH 11.2 > pH 8.2 > pH 2.4), while variations in the environmentally relevant ionic strengths (0.01 M NaCl + 0.01 M NaHCO3 and 0.04 M NaCl + 0.01 M NaHCO3) and the presence of dissolved natural organic matter (10 mg/L) do not affect release rate greatly. X-ray Absorption Near Edge Structure results suggest that phosphate adsorbed on the pristine 50 nm anatase desorbs, and some dissolved phosphate again re-sorbs as a surface precipitate. The findings from this research may have important environmental implications such as accidental release of TiO2 NPs and other nanomaterials that are synthesized using phosphorus containing chemicals as an ingredient.

A novel MYOC heterozygous mutation identified in a Chinese Uygur pedigree with primary open-angle glaucoma.

PURPOSE: To characterize the clinical features of a Chinese Uygur pedigree with primary open-angle glaucoma (POAG) and to identify mutations in two candidate genes, trabecular meshwork inducible glucocorticoid response (MYOC/TIGR) and human dioxin-inducible cytochrome P450 (CYP1B1). METHODS: Twenty one members from a Chinese Uygur family of four generations were included in the study. All participants underwent complete ophthalmologic examinations. Five were diagnosed as POAG, four as glaucoma suspects, and the rest were asymptomatic. Molecular genetic analysis was performed on all subjects included in the study. All exons of CYP1B1 and MYOC were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. The variations detected were evaluated in available family members as well as 102 normal controls. Possible changes in structure and function of the protein induced by amino acid variance were predicted by bioinformatics analysis. RESULTS: Elevated intraocular pressure and late-stage glaucomatous cupping of the optic disc were found in five patients of this family. A novel heterozygous missense mutation c.1151 A>G in exon 3 of MYOC was found in all five patients diagnosed as POAG and four glaucoma suspects, but not in the rest of the family members and 102 normal controls. This mutation caused an amino acid substitution of aspartic acid to glycine at position 384 (p. D384G) of the MYOC protein. This substitution may cause structural and functional changes of the protein based on bioinformatics analysis. No mutations were found in CYP1B1. CONCLUSIONS: Our study suggests that the novel mutation D384G of MYOC is likely responsible for the pathogenesis of POAG in this pedigree.

Is low dose of estrogen beneficial for prevention of glaucoma?

Glaucoma, as characterized by accelerated retinal ganglion cell (RGC) death and cupping of optic nerve head (ONH), is one of the leading causes of blindness worldwide. Elevated intraocular pressure (IOP) is generally considered as a major risk factor in the pathogenesis of glaucoma. Previous studies showed that glaucoma caused decrease in collagen and elastin density in several ocular tissues, such as lamina cribrosa, peripapillary sclera and cornea, and resulted in reduced elasticity and compliance of these tissues. It is known that estrogen has protective effects against glaucoma, yet the underlying mechanism still remains obscure. Prior researches have provided evidences showing that the estrogen receptors (ERs) express in a variety of the ocular tissues. Estrogen activates the synthesis of collagen fiber and improves the compliance of these tissues. This leads to a reasonable postulation that increased estrogen may result in a higher content of the collagen fibers and enhanced flexibility of the whole eye, which would therefore decrease IOP. Particularly, the increase in the amounts of collagen fibers at lamina cribrosa improves its compliance, which in turn relieves its compression on RGC axons. Therefore, even at the same IOP level, the softening of cribriform foramina yields a more flexible environment for the RGCs to survive. We therefore hypothesize that estrogen at proper dosage can be considered as a potential therapy for glaucoma since it is able to prevent the eye from glaucomatous damage and lower IOP, especially for those menopausal women with glaucoma.

Role of cerebrospinal fluid in glaucoma: pressure and beyond.

Glaucoma is the second leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is characterized by optic disc cupping and visual field impairment. Though the elevated intraocular pressure (IOP) is thought to be the major risk factor for POAG, about 50% of the POAG patients have normal IOP, called 'normal-tension' glaucoma. Besides, many POAG patients still experience visual field loss and/or optic disc cupping even though the IOP has been well controlled. The mechanisms underlying the pathogenesis of POAG remain unclear. Extensive studies have shed lights on the mechanisms that may be involved in the etiopathology and/or the optic neuropathic manifestations of POAG. In this article, we noticed that the changes in the cerebrospinal fluid, particularly that existing in the subarachnoid space of the optic nerve, appear to be actively involved in the pathogenesis of POAG.