Diurnal and circadian variations in intraocular pressure in goats exposed to different lighting conditions

ABSTRACT

The effect of constant light and constant darkness on intraocular pressure (IOP) in goats has not been investigated. We hypothesized that IOP variations would differ between goats kept under a cycle of 12 hours of light and 12 hours of darkness (LD), constant darkness (DD), and constant light (LL). To test this hypothesis, goats were exposed to these conditions for five days (LD, 30 goats; DD, 10 goats; LL, 10 goats). IOP was measured by applanation tonometry at 9 a.m. (beginning of photophase in LD) and 9 p.m. (beginning of scotophase in LD) on the fourth and fifth days of exposure. We found that changes in mean IOP from 9 a.m. to 9 p.m. differed significantly between groups (χ²(2) = 23.04, p < .0001). Most goats in LD showed a regular pattern of higher IOP in the morning and lower IOP in the evening, whereas those in DD and LL did not follow this pattern. In LD conditions, mean IOP was 2.4 mm Hg lower at 9 p.m. than at 9 a.m. (95% confidence interval for the difference (CI): ?2.8 to ?1.9 mm Hg, p < .0001). In DD conditions, mean IOP did not differ between 9 p.m. and 9 a.m. (CI: ?0.9 to 0.8 mm Hg, p = .90). In LL conditions, it was 0.6 mm Hg lower at 9 p.m. (CI: ?1.5 to 0.2 mm Hg, p = .12). Our results indicate that IOP in goats kept in LD is higher in the morning than in the evening, and that IOP variations are reduced in goats kept in DD and LL. These results suggest that exposure to alternating periods of light and darkness is important for maintaining rhythmic variations in IOP in this species.     

Intraocular pressure (IOP) in relation to four levels of daily geomagnetic and extreme yearly solar activity

The link between geomagnetic field activity (GMA), solar activity and intraocular pressure (IOP) in healthy individuals was investigated. The IOP of 485 patients (970 eyes) was recorded over three nonconsecutive years (1979, 1986, 1989) which were characterized by maximal solar activity (1979, 1989) or minimal solar activity (1986). The measurements were also correlated with four categories of GMA activity: quiet (level I⁰), unsettled (II⁰), active (III⁰), and stormy (IV⁰). Participants were also differentiated by age and sex. We found that IOP was lowest on days of level IV⁰ (stormy) GMA. The drop in IOP concomitant with a decrease in GMA level was more significant during periods of low solar activity and in persons over 65 years of age. There was a trend towards higher IOP values on days of levels II⁰ and IV⁰ GMA in years of high solar activity. Differences between the sexes and among individuals younger than 65 years were not significant. Our results show an interesting aspect of environmental influence on the healthy population.     

Low expression of GSTP1 in the aqueous humour of patients with primary open-angle glaucoma

Primary open-angle glaucoma (POAG) is characterized by irreversible neurodegeneration accompanied by visual field defects and high intraocular pressure. Currently, an effective treatment is not available to prevent the progression of POAG, other than treatments to decrease the high intraocular pressure. We performed proteomic analysis of aqueous humour (AH) samples from patients with POAG combined with cataract and patients with cataract to obtain a better understanding of the pathogenesis of POAG and explore potential treatment targets for this condition. Samples were collected from 10 patients with POAG combined with cataract and 10 patients with cataract. Samples from each group were pooled. A high-resolution, label-free, liquid chromatography-tandem mass spectrometry-based quantitative proteomic analysis was performed. In total, 610 proteins were identified in human AH samples from the two groups. A total of 48 up-regulated proteins and 49 down-regulated proteins were identified in the POAG combined with cataract group compared with the control group. Gene Ontology (GO) analysis revealed key roles for these proteins in inflammation, immune responses, growth and development, cellular movement and vesicle-mediated transport in the biological process category. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the down-regulated expression of glutathione S-transferase P (GSTP1) in the glutathione metabolism signalling pathway in the POAG combined with cataract group. Additionally, certain significantly differentially expressed proteins in the proteomic profile were verified by enzyme-linked immunosorbent assay (ELISA). GSTP1 levels were reduced in the human AH samples from the POAG combined with cataract group, based on the results of ELISA and proteomic profiling. Therefore, GSTP1, a redox-related marker, may be involved in the pathological process of POAG and may become a treatment target in the future.     

A pilot study to evaluate the levels of aqueous humor trace elements in open-angle glaucoma

BackgroundPrimary open angle glaucoma (POAG) is the most common form of chronic, progressive optic neuropathies characterized by slow degeneration of the retinal ganglion cells and their axons, resulting in visual field loss. Risk factors for this disease are elevated intraocular pressure (IOP), increased age, European and African ethnicity, family history, myopia and decreased corneal thickness. In addition, studies indicated that levels of trace elements are also significantly related to the POAG.MethodThe association between toxic and essential elements and POAG was explored in a population-based case–control study in the Sardinia Island (Italy). The aqueous humor levels of Al, Cd, Cu, Fe, Hg, Mn, Ni, Pb and Zn were measured in 25 POAG patients compared to 20 age- and gender-matched healthy controls by sector field inductively coupled mass spectrometry. Risk factors as gender, age and increased IOP were also explored.ResultsThe concentrations of Fe, Hg and Zn were significantly higher in POAG patients than in control subjects, showing these elements as possible determinants in POAG development or degeneration. Other findings were the increased Cu and Fe levels in glaucomatous patients with age less than 70 years. Levels of Ni were found elevated in POAG females. Mercury accumulated more in POAG females, in patients over 70 years and in those with higher levels of IOP in the left eye. Moreover, the positive associations CuFe and Mn-Zn may indicate synergistic effects of elements.ConclusionsAltogether, these findings suggested a multifactorial role in the risk for POAG disease. The present study documented the levels of trace elements in aqueous humor of Sardinian POAG patients for the first time.     

DNA damage evaluated by the comet assay in lymphocytes of children with Cs internal contamination caused by the Chernobyl accident

The comet assay is one of the most versatile and popular tools for evaluating DNA damage. Its sensitivity to low dose radiation has been tested in vitro, but there are limited data showing its application and sensitivity in chronic exposure situations. The influence of the internal contamination caused by the Chernobyl accident on the level of DNA damage was evaluated by the comet assay on lymphocytes of 56 Ukrainian children. The study was performed during 2003 on children with demonstrable ¹³⁷Cs internal contamination caused by food consumption. The children were selected for the study immediately after a ¹³⁷Cs whole body counter measurement of internal contamination. The minimal detectable amount of ¹³⁷Cs was 75 Bq. The control group included 29 children without detectable internal contamination, while in the exposed group 27 children with measured activity between 80 and 4037 Bq and committed effective dose between 54 and 3155 μSv were included. Blood samples were taken by a finger prick. The alkaline version of the comet assay was used, in combination with silver stained comets and arbitrary units (AU), for comet measurement. Factors such as disease, medical treatment, surface contamination of children's living location, etc., were considered in the study. Non-significant differences (p > 0.05) in DNA damage in control (9.0 ± 5.7 AU) versus exposed (8.5 ± 4.8 AU) groups were found. These results suggest that low doses of ¹³⁷Cs internal contamination are not able to produce detectable DNA damage under the conditions used for the comet assay in this study. Further studies considering effects of high exposure should be performed on chronically exposed people using this assay.     

New mutation in the myocilin gene segregates with juvenile-onset open-angle glaucoma in a Brazilian family

Mutations in the myocilin gene (MYOC) account for most cases of autosomal dominant juvenile-onset open-angle glaucoma (JOAG), an earlier and more severe form of POAG. We accessed seven members of a Brazilian JOAG family by clinical and molecular investigation. Four out of seven family members were diagnosed with JOAG. All of these patients presented high intraocular pressure and two of them were bilaterally blind. The disease onset varied from 20 to 30 years old. There was a nine-year-old family member who had not yet manifested the disease, although he was also a carrier of the mutation. Ophthalmologic examination included: evaluation of the visual field and optic disc, intraocular pressure measurement, and gonioscopy. The three exons and intron/exon junctions of the MYOC gene were screened for mutations through direct sequencing of PCR-amplified DNA fragments. Mutation screening revealed an in-frame mutation in the third exon of the MYOC gene: an insertion of six nucleotides between the cDNA positions 1187 and 1188 (c.1187_1188insCCCAGA, p.D395_E396insDP). This mutation presented an autosomal dominant pattern of inheritance, segregating with the disease in four family members for three generations, and it was absent in 60 normal controls. We also performed a computational structure modeling of olfactomedin-like domain of myocilin protein and conducted in silico analysis to predict the structural changes in the myocilin protein due to the presence of the mutation. These findings may be important for future diagnosis of other presymptomatic family members, as well as for the increase of the panel of MYOC mutations and their effects on phenotype.     

Effects of intravitreous sodium hydrosulfide on intraocular pressure and retinopathy in ocular hypertensive rats

We investigated the possible neuroprotectant and intraocular pressure (IOP) lowering effects of intravitreous injection of sodium hydrosulfide (NaSH) in a rodent model of experimental glaucoma. Glaucoma currently is treated by controlling IOP using medications and/or surgery. These methods are not entirely adequate for all patients. We divided 24 rats into three groups. For the control group, the right eye was treated with intravitreous saline. For the glaucoma group, ocular hypertension was induced by photocoagulating three episcleral veins and the limbal plexus of the right eye using an argon laser, then saline was injected into the vitreous of these eyes during the third week. For the NaSH group, rats were treated with intravenous NaSH 3 weeks after photocoagulation. IOP was measured each week during the 6 week experimental period. Coagulating the episcleral veins rapidly increased the IOP of rat eyes. Intravitreous injection of NaSH significantly reduced IOP. Intravitreous NaSH prevented degeneration of the retina and decreased the number of apoptotic cells. Intravitreous NaSH appeared to reduce IOP and to prevent IOP induced retinopathy in rats.     

布林佐胺与噻吗洛尔滴眼液对新生血管性青光眼患者眼压及血清和房水IL-6、PEDF和VEGF水平的影响

目的:探讨布林佐胺联合噻吗洛尔滴眼液对新生血管性青光眼(NVG)患者眼压及血清和房水中白细胞介素-6(IL-6)、色素上皮衍生因子(PEDF)、血管内皮生长因子(VEGF)水平的影响。方法:选取我院2014年6月～2016年12月择期行手术治疗的86例NVG患者,按照随机数字表法均分为两组。对照组术后采取噻吗洛尔滴眼液治疗,观察组在此基础上加用布林佐胺滴眼液治疗。记录比较两组临床疗效,治疗前后眼压及血清和房水中IL-6、PEDF和VEGF水平的变化及不良反应的发生情况。结果:术后6个月,观察组总有效率为95.3%,较对照组明显升高(79.1%,P0.05)。与术前对比,两组术后7天、6个月时24 h眼压峰值、平均眼压、眼压波动值、血清和房水中IL-6、VEGF水平均显著下降(P0.01),血清和房水中PEDF水平均显著上升(P0.01),且观察组以上眼压指标较对照组同期改善更为明显(P0.01)。对照组和观察组不良反应的发生率对比差异无统计学意义(7.0%vs 11.6%,P0.05)。结论:术后应用布林佐胺联合噻吗洛尔滴眼液治疗NVG患者更能有效降低眼压和控制其波动,调节机体血管生成促进/抑制因子平衡,提高治疗效果,且安全性高。     

曲伏前列素滴眼液治疗开角型青光眼的疗效及对血流动力学的影响

目的:探讨曲伏前列素滴眼液治疗开角型青光眼的疗效及对血流动力学的影响。方法:选择2013年3月~2015年12月在我院接受治疗的164例开角型青光眼患者为研究对象,按照随机数字表法分为对照组和试验组,每组82例,对照组给予马来酸噻吗洛尔滴眼,试验组给予曲伏前列素滴眼,12周后观察两组患者的降眼压效果和视力改变情况,彩色多普勒超声检测眼动脉(OA)、睫状后短动脉(SPCA)及视网膜中央动脉(CRA)的收缩期血流峰值速度(PSV)、舒张末期血流速度(EDV)和阻力指数(RI),并观察其不良反应。结果:两组患者治疗前和治疗后2周的眼压和视力比较,差异无统计学意义(P0.05)。治疗后,两组患者的眼压与治疗前比较均降低,视力与治疗前比较均提升,且试验组眼压降低及视力提升更显著,差异有统计学意义(P0.05);治疗6周和12周后,试验组患者的眼压低于对照组,视力高于对照组,差异有统计学意义(P0.05)。治疗12周后试验组患者OA、SPCA及CRA的EDV、PSV均高于对照组,而RI均低于对照组,差异有统计学意义(P0.05)。两组患者的不良反应主要为轻度异物感、轻度结膜充血、虹膜色素加深等,两组患者的不良反应发生率比较,差异无统计学意义(P0.05)。结论:曲伏前列素滴眼液治疗开角型青光眼可降低眼压,提高视力,改善眼部血流动力学指标,且安全性较好,值得临床推广应用。     

Seasonal changes of leaf surface contamination in beech, oak, and ginkgo in relation to leaf micromorphology and wettability

The leaf surfaces of beech, oak and ginkgo have been investigated with respect to contamination with particles during one growing season. Based on the observation that particles are removed from water-repellent leaves by rain (Lotus effect) the three species were selected because they differ in leaf surface micromorphology and wettability. Leaves of beech are smooth, lacked wax crystals and were ±wettable. Those of ginkgo were rough because their cells were convex and were densely covered by wax crystals, resulting in permanent water repellency. Leaves of oak were covered by waxes and were water repellent when young, but, a few weeks after leaf expansion had ceased the waxes were rapidly eroded. These differences in wettability resulted in different amounts of contamination. Ginkgo collected a very small number of particles during the whole vegetation period. In beech the contamination was significantly higher, but fairly constant, whereas oak leaves accumulated particles with age.     

Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma

Glaucoma is conventionally defined as a chronic optic neuropathy characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Although glaucoma is often associated with elevated intraocular pressure (IOP), significant IOP reduction does not prevent progression of the disease in some glaucoma patients. Thus, exploring IOP-independent mechanisms of RGC loss is important. We describe chronic systemic administration of aldosterone and evaluate its effect on RGCs in rat. Aldosterone was administered via an osmotic minipump that was implanted subcutaneously into the mid-scapular region. Although systemic administration of aldosterone caused RGC loss associated with thinning of the retinal nerve fiber layer without elevated IOP, the other cell layers appeared to be unaffected. After chronic administration of aldosterone, RGC loss was observed at 2 weeks in the peripheral retina and at 4 weeks in the central retina. However, administration of mineralocorticoid receptor blocker prevented RGC loss. These results demonstrate aldosterone is a critical mediator of RGC loss that is independent of IOP. We believe this rat normal-tension glaucoma (NTG) animal model not only offers a powerful system for investigating the mechanism of neurodegeneration in NTG, but can also be used to develop therapies directed at IOP-independent mechanisms of RGC loss.     

曲伏前列腺素滴眼液对原发性开角型青光眼患者眼压、血流动力学及ET-1、TIMP-2的影响

目的:探讨曲伏前列腺素滴眼液对原发性开角型青光眼(POAG)患者眼压、血流动力学及内皮素-1(ET-1)、基质金属蛋白酶-2抑制因子(TIMP-2)的影响。方法:选取2015年2月至2017年2月我院眼科收治的70例患者,按照随机数字表法分为对照组和观察组,每组各35例,对照组和观察组患者分别给予马来酸噻吗洛尔滴眼液和曲伏前列腺素滴眼液治疗,治疗周期为3个月。对比分析治疗前、治疗4周、8周及12周后两组患者的平均眼压(IOP)、昼夜IOP差,并对比治疗前、治疗12周后的睫状后动脉(PCA)、视网膜中央动脉(CRA)、收缩期峰值血流速度(PSV)、舒张末期血流速度(EDV)、血管阻力指数(RI)、血浆ET-1及房水TIMP-2的改善情况。结果:治疗前两组患者平均IOP、昼夜IOP差、PCA和CRA血流动力学、血浆ET-1及房水TIMP-2差异无统计学意义(P0.05);治疗4周、8周、12周后,两组平均IOP、昼夜IOP差明显低于治疗前,且治疗12周后观察组平均IOP、昼夜IOP差低于对照组,差异均有统计学意义(P0.05);治疗12周后,观察组PCA和CRA的PSV、EDV高于治疗前,RI低于治疗前,差异均有统计学意义(P0.05),且观察组PCA和CRA的PSV、EDV高于对照组,RI低于对照组,差异均有统计学意义(P0.05);治疗12周后,两组患者血浆ET-1和房水TIMP-2较治疗前显著下降,且观察组血浆ET-1和房水TIMP-2含量低于对照组,差异均有统计学意义(P0.05)。结论:曲伏前列腺素滴眼液治疗POAG患者,能够有效降低患者的眼压、血浆ET-1、房水TIMP-2水平,并改善患者PCA、CRA的血流动力学。     

Elemental composition of the sub-aquatic liverwort Pellia endiviifolia (Dicks.) Dum. in relation to heavy metal contamination

The concentrations of fifteen elements (B, Na, Mg, Al, P, K, Ca, Ti, Mn, Fe, Cu, Zn, Sr, Cd, Pb) in thalli of the sub-aquatic liverwort Pellia endiviifolia (Dicks.) Dum. collected from seven sites in Japan, were analyzed by inductively coupled plasma atomic emission spectrometer (ICP). The average concentration of major essential elements in the thalli was: 49 600 µg g^–1 K, 9 140 µg g^–1 Na, 6740 µg g^–1 Ca, 3 840 µg g^–1 P, and 3 060 µg g^–1 Mg. Thalli of P. endiviifolia from sites polluted by heavy metals (Cu, Zn, Pb) contained high concentrations of these elements (maxima 0.88% Cu, 0.55% Zn and 0.36% Pb in the older thallus), thus demonstrating the potentiality of this liverwort as an indicator for heavy metal contamination.     

Structural and ultrastructural analysis of gills and gut of Hexagenia rigida nymphs (ephemeroptera) in relation to contamination mechanisms

In the context of an experimental approach to organic and inorganic mercury bio-accumulation by burrowing mayfly nymphs-Hexagenia rigida-, gills and different parts of the gut were investigated by light and electron microscopes. In the gut, two regions were studied: (1) mesenteron (midgut) characterized by cells with microvilli and a peritrophic membrane throughout this part, a lot of fungal hyphae being found on it; (2) proctodeum (hindgut) characterized by macrovilli, the apical face of cells being covered by a thick layer of chitin; many bacteria were observed at the bottom of macrovilli. The stomodeum (foregut) is extremely short. The gills are made up of six pairs of lamellae fringed with long filaments which are arranged on both sides of the long axis. Gills are constituted by tracheae and tracheoles, with a large canal for haemolymph circulation; muscle masses and nerve bundles were also observed. This structural approach shows that the nymph interface with the external environment, at gill and gut barrier levels, are quite different. Links between this structural and ultrastructural analysis and contamination mechanisms, via the trophic or direct route, are discussed; gills and gut could be transfer routes for mercury absorption, but also target organs for metal accumulation.     

Blood pressure and heart rate variability are linked with hyperphosphatemia in chronic kidney disease patients

ABSTRACT

Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and is associated with cardiovascular disease (CVD), which has contributed to an increase in mortality of CKD patients. The onset of CVD often varies by time-of-day. Acute myocardial infarction or ventricular arrhythmia occurs most frequently during early morning. Blood pressure (BP) and heart rate circadian rhythms account for the diurnal variations in CVD. Preservation of normal circadian time structure from the cardiomyocyte level to the whole organ system is essential for cardiovascular health and CVD prevention. Independent risk factors, such as reduced heart rate variability (HRV) and increased BP variability (BPV), are particularly prevalent in patients with CKD. Analysis of HRV is an important clinical tool for characterizing cardiac autonomic status, and reduced HRV has prognostic significance for various types of CVD. Circadian BP rhythms are classified as extreme dipper, dipper, non-dipper or riser. It has been reported that nocturnal riser BP pattern contributes to cardiovascular threats. Previous studies have indicated that the circadian rhythm of serum phosphate in CKD patients is consistent with the general population, with the highest diurnal value observed in the early morning hours, followed by a progressive decrease to the lowest value of the day, which occurs around 11:00 am. Rhythm abnormalities have become the main therapeutic target for treating CVD in CKD patients. It has been reported that high levels of serum phosphate are associated with reduced HRV and increased BPV in CKD patients. However, the mechanisms related to interactions between hyperphosphatemia, HRV and BPV have not been fully elucidated. This review focuses on the evidence and discusses the potential mechanisms related to the effects of hyperphosphatemia on HRV and BPV.