Intraocular pressure in cats is lowered by drops of hornet venom

1. Nine cats were given an intravenous injection of the Oriental hornet (Vespa orientalis, Vespinae; Hymenoptera) venom sac extract (VSE) and seven cats had the same VSE administered as eye drops. 2. When injected intravenously, the hornet VSE decreased the intraocular pressure in both eyes sharply during the first 20 min and with a slower rate later on until the end of the 3 hr experiment. The intraocular pressure dropped to zero in some cases. 3. VSE eye drops decreased the intraocular pressure only in the treated eye, while in the second eye (left as a control) the intraocular pressure remained the same throughout the experiment. 4. The decrease in the intraocular pressure was sharp during the first 20 min and slowed down afterwards until the end of the experiment. 5. The intraocular pressure did not reduce to zero. 6. This study shows that the active components of the hornet venom which caused a decrease in the intraocular pressure can cross the cornea and exert a hypotensive effect in the eye.     

G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension

The tone of vascular smooth muscle cells is a primary determinant of the total peripheral vascular resistance and hence the arterial blood pressure. Most forms of hypertension ultimately result from an increased vascular tone that leads to an elevated total peripheral resistance. Regulation of vascular resistance under normotensive and hypertensive conditions involves multiple mediators, many of which act through G protein-coupled receptors on vascular smooth muscle cells. Receptors that mediate vasoconstriction couple with the G-proteins G(q)-G11 and G12-G13 to stimulate phosphorylation of myosin light chain (MLC) via the Ca2+/MLC kinase- and Rho/Rho kinase-mediated signaling pathways, respectively. Using genetically altered mouse models that allow for the acute abrogation of both signaling pathways by inducible Cre/loxP-mediated mutagenesis in smooth muscle cells, we show that G(q)-G11-mediated signaling in smooth muscle cells is required for maintenance of basal blood pressure and for the development of salt-induced hypertension. In contrast, lack of G12-G13, as well as of their major effector, the leukemia-associated Rho guanine nucleotide exchange factor (LARG), did not alter normal blood pressure regulation but did block the development of salt-induced hypertension. This identifies the G12-G13-LARG-mediated signaling pathway as a new target for antihypertensive therapies that would be expected to leave normal blood pressure regulation unaffected.     

汉防己甲素滴眼液对高眼压模型大鼠的降眼压作用

目的比较观察汉防己甲素滴眼液与0.5%噻吗心安滴眼液对高眼压模型大鼠及正常大鼠降眼压的作用。方法正常SD大鼠共分4组：不同浓度的汉防己甲素滴眼液组（0.1%、0.2%、0.3%）及阳性对照组0.5%噻吗心安,药物滴右眼各一滴,阴性对照组生理盐水滴左眼、测量滴药前24h和滴药后1、3、6、24、48、72h的眼压。应用倍频532激光对SD大鼠右眼上巩膜静脉以及小梁网所在区域实施光凝术建立高眼压大鼠模型。高眼压模型鼠共分5组：不同浓度的汉防己甲素滴眼液0.05%、0.1%、0.2%、0.3%及阳性对照组0.5%噻吗心安,右眼即模型眼滴用药物,左眼作为空白对照。测量术前后的眼压。结果汉防己甲素滴眼液对大鼠正常眼压无降压作用（P〉0.05）。对高眼压大鼠用药后24h、72h、1周后,0.3%汉防己甲素滴眼液组降低眼压的幅度与0.5%噻吗心安滴眼液降低眼压的幅度相似（P〉0.05）;0.05%、0.1%、0.2%汉防己甲素滴眼液组也有明显的降压作用,但与0.5%噻吗心安滴眼液相比,降压幅度低于后者（P〈0.05）。结论0.05%、0.1%、0.2%、0.3%汉防己甲素滴眼液均有降低大鼠高眼压的作用,其中0.3%浓度的汉防己甲素滴眼液降眼压效果与0.5%的噻吗心安类似。汉防已甲素滴眼液作为一种治疗青光眼的药物有着良好应用前景。     

Effects of the R(+)- and S(-)-isomers of beta-adrenoceptor blockers with intrinsic sympathomimetic activity, befunolol and carteolol, on rabbit intraocular pressure.

Effects of the R(+)- and S(-)-isomers of befunolol and carteolol, beta-adrenoceptors with intrinsic sympathomimetic activity, on the rabbit intraocular pressure were tested. The intraocular pressure was decreased by instillation of the R(+)- and S(-)-isomers of befunolol (0.1 and 0.3%) and of carteolol (1.0%) to the eye and attained the minimum level at 60 min. However, 0.3% of the R(+)- and S(-)-isomers of carteolol did not influence the pressure. The corresponding time courses for the intraocular pressure for the R(+)- and S(-)-isomers did not differ, suggesting that in the treatment of glaucoma, the therapeutic advantage of the R(+)-isomers of befunolol and carteolol may be similar to the S(-)-isomers.     

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。     

Carnitine reduces the lipoperoxidative damage of the membrane and apoptosis after induction of cell stress in experimental glaucoma

The pathological damage caused by glaucoma is associated to a high intraocular pressure. The ocular hypertone is most likely due to a defective efflux of aqueous humor from the anterior chamber of the eye. Ocular hypertension causes apoptotic death of retinal ganglion cells and overexpression of molecular markers typical of cell stress response and apoptosis. In this work, we report on the neuroprotective, antiapoptotic and antioxidant action of a natural substance, -carnitine. This compound is known for its ability to improve the mitochondrial performance. We analyze a number of cellular and molecular markers, typical of ocular hypertension and, in general, of the cell stress response. In particular, -carnitine reduces the expression of glial fibrillary acidic protein, inducible nitric oxide synthase, ubiquitin and caspase 3 typical markers of cell stress. In addition, the morphological analysis of the optic nerve evidenced a reduction of the pathological excavation of the optic disk. This experimental hypertone protocol induces a severe lipoperoxidation, which is significantly reduced by -carnitine. The overall interpretation is that mortality of the retinal cells is due to membrane damage.     

Sympathetic activation and nitric oxide function in early hypertension

The purpose of this study was to determine if tonic restrain of blood pressure by nitric oxide (NO) is impaired early in the development of hypertension. Impaired NO function is thought to contribute to hypertension, but it is not clear if this is explained by direct effects of NO on vascular tone or indirect modulation of sympathetic activity. We determined the blood pressure effect of NO synthase inhibition with N(ω)-monomethyl-l-arginine (L-NMMA) during autonomic blockade with trimethaphan to eliminate baroreflex buffering and NO modulation of autonomic tone. In this setting, impaired NO modulation of vascular tone would be reflected as a blunted pressor response to L-NMMA. We enrolled a total of 66 subjects (39 ± 1.3 yr old, 30 females), 20 normotensives, 20 prehypertensives (blood pressure between 120/80 and 140/90 mmHg), 17 hypertensives, and 9 smokers (included as "positive" controls of impaired NO function). Trimethaphan normalized blood pressure in hypertensives, suggesting increased sympathetic tone contributing to hypertension. In contrast, L-NMMA produced similar increases in systolic blood pressure in normal, prehypertensive, and hypertensive subjects (31 ± 2, 32 ± 2, and 30 ± 3 mmHg, respectively), whereas the response of smokers was blunted (16 ± 5 mmHg, P = 0.012). Our results suggest that sympathetic activity plays a role in hypertension. NO tonically restrains blood pressure by ～30 mmHg, but we found no evidence of impaired modulation by NO of vascular tone contributing to the early development of hypertension. If NO deficiency contributes to hypertension, it is likely to be through its modulation of the autonomic nervous system, which was excluded in this study.     

Regional variation of corneal stromal deformation measured by high-frequency ultrasound elastography

The cornea’s mechanical response to intraocular pressure elevations may alter in ectatic diseases such as keratoconus. Regional variations of mechanical deformation in normal and keratoconus eyes during intraocular pressure elevation have not been well-characterized. We applied a high-frequency ultrasound elastography technique to characterize the regional deformation of normal and keratoconus human corneas through the full thickness of corneal stroma. A cross-section centered at the corneal apex in 11 normal and 2 keratoconus human donor eyes was imaged with high-frequency ultrasound during whole globe inflation from 5 to 30 mmHg. An ultrasound speckle tracking algorithm was used to compute local tissue displacements. Radial, tangential, and shear strains were mapped across the imaged cross-section. Strains in the central (1 mm surrounding apex) and paracentral (1 to 4 mm from apex) regions were analyzed in both normal and keratoconus eyes. Additional regional analysis was performed in the eye with severe keratoconus presenting significant thinning and scarring. Our results showed that in normal corneas, the central region had significantly smaller tangential stretch than the paracentral region, and that within the central region, the magnitudes of radial and shear strains were significantly larger than that of tangential strain. The eye with mild keratoconus had similar shear strain but substantially larger radial strains than normal corneas, while the eye with severe keratoconus had similar overall strains as in normal eyes but marked regional heterogeneity and large strains in the cone region. These findings suggested regional variation of mechanical responses to intraocular pressure elevation in both normal and keratoconus corneas, and keratoconus appeared to be associated with mechanical weakening in the cone region, especially in resisting radial compression. Comprehensive characterization of radial, tangential, and shear strains through corneal stroma may provide new insights to understand the biomechanical alterations in keratoconus.     

Iridodialysis in a rhesus macaque: a case report

During routine physical examination, a five-year-old male rhesus macaque (Macaca mulatta) was observed to have gaps in the right iris. Ophthalmic examination revealed inferior and superior iridodialysis with an anterior cortical cataract. The optic nerve head and fundus were normal. Uninvolved areas of the iris and anterior-chamber angle were normal on the basis of results of gonioscopy. Tonometry revealed normal intraocular pressure. The cause of the iridodialysis in this monkey's eye was not known. The animal had been housed individually since arrival due to requirements of the research protocol. Although the concomitant cataract supports a traumatic cause, there was no history of cranial or other ocular injuries. Trauma from fighting through the cage walls, self-trauma or falling inside the cage while under sedation cannot be ruled out. Multiple hematologic evaluations disclosed no abnormalities. This animal did not manifest behavioral abnormalities or any indication of pain. Therefore, treatment was not initiated. Intraocular pressure continues to be monitored at least semiannually.     

Role of endogenous prostaglandins in regulating the tone of opossum lower esophageal sphincter in vivo.

The role of prostaglandins in maintenance of basal myogenic tone of the lower esophageal sphincter (LES) of opossum has been studied in vivo. Intra-arterial infusion of arachidonic acid decreased LES tone, and this was inhibited by intravenous indomethacin (IDM) or intra-arterial 5,8,11,14-eicosatetraynoic acid (ETA). Alone these drugs did not reduce LES tone except transiently. In addition they did not affect relaxation of the LES to distention of a balloon located proximal to it or inhibit the "off" contractions of esophageal body and LES pressure which followed balloon deflation. Spontaneous oscillations of LES pressure were increased with IDM. Thus prostaglandin synthesis plays no essential role in maintenance of resting LES tone or in functioning of non-adrenergic inhibitory nerves in the esophagus in vivo. Endogenous inhibitory prostaglandins might reduce LES tone if synthesized in increased amounts.     

Biomechanical adaptation of porcine carotid vascular smooth muscle to hypo and hypertension in vitro

Previous research in arterial remodeling in response to changes in blood pressure seldom included both hyper- and hypotension. To compare the effects of low and high pressure on arterial remodeling and vascular smooth muscle tone and performance, we have utilized an in vitro model. Porcine carotid arteries were cultured for 3 days at 30 and 170mmHg and compared to controls cultured at 100mmHg for 1 and 3 days. On the first and last day of culture, pressure-diameter and pressure-wall thickness curves were measured under normal smooth muscle tone using a high-resolution ultrasonic device. Last-day experiments included measurements where vascular smooth muscle was contracted or totally relaxed. From the data wall cross-sectional area, Hudetz elastic modulus and a contraction index related to the diameter reduction under normal smooth muscle tone were calculated. We found that although wall cross-sectional area (indicating wall mass) did not change much, Hudetz elastic modulus was significantly reduced in the 3-day hypotension group. Inspection of the wall contraction index suggests that this is due to a reduction in the vascular smooth muscle tone. Further, the peak of contraction index was found to be shifted to higher pressures in the 3-day 170mmHg group. We conclude that vascular smooth muscle performance adapts to both hypo- and hypertension at short time scales and can alter the biomechanics of the vascular wall in vitro.     

Differential regulation of insulin resistance and hypertension by sex hormones in fructose-fed male rats

Differences in gender are in part responsible for the development of insulin resistance (IR) and associated hypertension. Currently, it is unclear whether these differences are dictated by gender itself or by the relative changes in plasma estrogen and/or testosterone. We investigated the interrelationships between testosterone and estrogen in the progression of IR and hypertension in vivo in intact and gonadectomized fructose-fed male rats. Treatment with estrogen significantly reduced the testosterone levels in both normal chow-fed and fructose-fed rats. Interestingly, fructose feeding induced a relative increase in estradiol levels, which did not affect IR in both intact and gonadectomized fructose-fed rats. However, increasing the estrogen levels improved insulin sensitivity in both intact and gonadectomized fructose-fed rats. In intact males, fructose feeding increased the blood pressure (140 +/- 2 mmHg), which was prevented by estrogen treatment. However, the blood pressure in the fructose-fed estrogen rats (125 +/- 1 mmHg) was significantly higher than that of normal chow-fed (113 +/- 1 mmHg) and fructose-fed gonadectomized rats. Estrogen treatment did not affect the blood pressure in gonadectomized fructose-fed rats (105 +/- 2 mmHg). These data suggest the existence of a threshold value for estrogen below which insulin sensitivity is unaffected. The development of hypertension in this model is dictated solely by the presence or absence of testosterone. In summary, the development of IR and hypertension is governed not by gender per se but by the interactions of specific sex hormones such as estrogen and testosterone.     

Effect of the Na-K-2Cl cotransporter NKCC1 on systemic blood pressure and smooth muscle tone

Studies in rat aorta have shown that the Na-K-2Cl cotransporter NKCC1 is activated by vasoconstrictors and inhibited by nitrovasodilators, contributes to smooth muscle tone in vitro, and is upregulated in hypertension. To determine the role of NKCC1 in systemic vascular resistance and hypertension, blood pressure was measured in rats before and after inhibition of NKCC1 with bumetanide. Intravenous infusion of bumetanide sufficient to yield a free plasma concentration above the IC(50) for NKCC1 produced an immediate drop in blood pressure of 5.2% (P < 0.001). The reduction was not prevented when the renal arteries were clamped, indicating that it was not due to a renal effect of bumetanide. Bumetanide did not alter blood pressure in NKCC1-null mice, demonstrating that it was acting specifically through NKCC1. In third-order mesenteric arteries, bumetanide-inhibitable efflux of (86)Rb was acutely stimulated 133% by phenylephrine, and bumetanide reduced the contractile response to phenylephrine, indicating that NKCC1 influences tone in resistance vessels. The hypotensive effect of bumetanide was proportionately greater in rats made hypertensive by a 7-day infusion of norepinephrine (12.7%, P < 0.001 vs. normotensive rats) but much less so when hypertension was produced by a fixed aortic coarctation (8.0%), again consistent with an effect of bumetanide on resistance vessels rather than other determinants of blood pressure. We conclude that NKCC1 influences blood pressure through effects on smooth muscle tone in resistance vessels and that this effect is augmented in hypertension.     

The gaseous messenger carbon monoxide is released from the eye into the ophthalmic venous blood depending on the intensity of sunlight

Circadian and seasonal rhythms in daylight affect many physiological processes. In the eye, energy of intense visible light not only initiates a well-studied neural reaction in the retina that modulates the secretory function of the hypothalamus and pineal gland, but also activates the heme oxygenase (HO) to produce carbon monoxide (CO). This study was designed to determine whether the concentration of carbon monoxide (CO) in the ophthalmic venous blood changes depending on the phase of the day and differing extremely light intensity seasons: summer and winter. The concentration of CO in the venous blood flowing out from the nasal cavity, where heme oxygenase (HO) is expressed, but no photoreceptors, was used as a control. Sixteen mature males of a wild boar and pig crossbreed were used for this study. Samples of ophthalmic and nasal venous blood and systemic arterial and venous blood were collected repeatedly for two consecutive days during the longest days of the summer and the shortest days of the winter. The concentrations of CO in blood samples was measured using a standard addition method. During the longest days of the summer the concentration of CO in ophthalmic venous blood averaged 3.32 ± 0.71 and 3.43 ± 0.8 nmol/ml in the morning and afternoon, respectively, and was significantly higher than in the night averaging 0.89 ± 0.12 nmol/ml (p<0.001). During the shortest day of the winter CO concentration in ophthalmic venous blood was 1.11 ± 0.10 and 1.13 ± 0.14 nmol/ml during the light and nocturnal phase, respectively, and did not differ between phases, but was lower than in the light phase of the summer (p<0.01). The CO concentration in the control nasal venous blood did not differ between seasons and day phases and was lower than in ophthalmic venous blood during the summer (p<0.01) and winter (p<0.05). The results indicate that the gaseous messenger carbon monoxide is released from the eye into the ophthalmic venous blood depending on the intensity of sunlight.     

Role of endogenous prostaglandins in regulating the tone of opossum lower esophageal sphincter in vivo

The role of prostaglandins in maintenance of basal myogenic tone of the lower esophageal sphincter (LES) of opossum has been studied $\text{in vivo}$. Intra-arterial infusion of arachidonic acid decreased LES tone, and this was inhibited by intravenous indomethacin (IDM) or intra-arterial 5,8,11,14-eicosatetraynoic acid (ETA). Alone these drugs did not reduce LES tone except transiently. In addition they did not affect relaxation of the LES to distention of a balloon located proximal to it or inhibit the “off” contractions of esophageal body and LES pressure which followed balloon deflation. Spontaneous oscillations of LES pressure were increased with IDM. Thus prostaglandin synthesis plays no essential role in maintenance of resting LES tone or in functioning of non-adrenergic inhibitory nerves in the esophagus $\text{in vivo}$. Endogenous inhibitory prostaglandins might reduce LES tone if synthesized in increased amounts.     

Effect of carnosine on intraocular pressure

It has been demonstrated in experiments on non-anesthetized rabbits that conjunctival injection of carnosine (beta-alanyl 1-histidine) caused a decrease in normal intraocular pressure and reduced prostaglandin-induced ocular hypertension. The rapid onset of the pressure response and the absence of papillary dilation in rabbits treated with carnosine were observed. It is concluded that L-carnosine can be used as a potent drug for the prevention of reactive hypertension syndrome.     

Corneal thickness in congenital glaucoma

Central corneal thickness is very important measurement in glaucoma treatment because it influences the eye pressure measurements. A thinner cornea gives us artifactually lower intraocular pressure and a thicker cornea gives higher intraocular pressure reading, so it has to be corrected in both cases. The aim of this study is to compare central corneal thickness between congenital glaucoma patients and normal subjects. Prospective study included 27 patients with congenital glaucoma and 35 patients in control group. First group was subdivided in two subgroups: A--8 earlier operated patients, B--19 patients treated with topic therapy. Patients had no other corneal disorders, history of trauma, corneal surgery and they were not contact lens wearers. Measurements were performed by specular microscope Tomey EM 3000 on central corneas. This study showed that patients with congenital glaucoma have lower central corneal thickness than normal subjects. Also, the study showed that antiglaucomatous operation doesn't influence central corneal thickness. Central corneal thickness need to be a routine part of examination measurements because of need to correct intraocular pressure according to it, but also the thinner corneas values can suggest congenital glaucoma diagnosis beside the other parameters.     

Pressure balance and imbalance in the optic nerve chamber: The Beijing Intracranial and Intraocular Pressure (iCOP) Study

To determine the interdependence of intracranial pressure (ICP) and intraocular pressure (IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure (LCP), optic nerve subarachnoid space pressure (ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP (via shunting cerebrospinal fluid (CSF) from the ventricle) were recorded. At baseline, all examined pressures were different (ICP<LCP<ONSP), but correlated (P>0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient (TLPG) remained stable (ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined (ICP-IOP independent zone). The optic nerve pressure gradient (ONPG) and trans-optic nerve pressure gradient (TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.     

Intravenous methylprednisolone in the treatment of Graves' ophthalmopathy.

Eleven euthyroid patients with severe Graves'' eye disease were treated with intravenous methylprednisolone and followed up for six months or more by ophthalmological assessment, orbital computed tomography (CT), photographs, and antibody measurements. Papilloedema resolved in the single patient in whom it was present; visual acuity was abnormal in seven eyes initially and in only one eye after treatment; the intraocular pressure differential, which reflects muscle dysfunction, was initially abnormal in 18 eyes but showed a progressive and distinct improvement; nine patients showed substantial improvement in inflammatory signs. Exophthalmos improved early after treatment, but this improvement was not maintained. Orbital CT showed a pronounced reduction in the bulk of eye muscles after treatment in eight of nine patients. Autoantibodies to the thyroid stimulating hormone receptor declined. Adverse effects were trivial. Thus eight patients showed a clear response to intravenous methylprednisolone as judged by ophthalmic assessment and CT scan. The two patients who showed little response and one who had none all had a long history (more than a year) of ophthalmopathy. Results were better than those with oral steroids and adverse effects less. Treatment of Graves'' eye disease is more likely to be effective if given early; patients should be referred promptly to specialist centres, where treatment with intravenous methylprednisolone should be considered.