拉坦前列素对青光眼治疗作用

拉坦前列素（latanoprost)是一种新的苯基替代前列腺素衍生物，它的作用机制是通过调节房水经巩膜－脉胳膜通道来达到降压，它与睫状肌上的FP受体结合后调节此通道的房水流出，另外，前列腺素（PGs)本身对细胞骨架有收缩作用，因此，它很有可能也在较大地影响着小梁网的房水流量从而降低眼压。     

前列腺素对眼压及青光眼的影响

近年来关于前列腺素的研究进展十分迅速,已知前列腺素(Prostaglandins简称PG_s)是具有很强生物活性的脂类自体活性物质,是细胞功能的局部调节介质。早期实验表明:前列腺素是眼部炎症的主要调节物,它参与人和动物的外伤性炎症反应和免疫性炎症反应过程,包括血-房水屏障的破坏、血管通透性增强、房水闪光、房水蛋白含量升高等炎症现象及瞳孔缩小与眼压升高。因此人们的注意力多集中到使用PG_s合成抑制剂来预防或减轻眼部炎症方面。而这些自体括性物质在正常眼前部生理作用以及其衍生物(同分异构体)的治疗作用在很大程度上却被忽视了。近年来的许多实验已证明局部应用适当剂量的PG_s或其衍生物能有效地降低数种实验动物的眼压,其降压效果明显地优于常规使用的抗青光眼类药物,而这些低剂量的PG_s并未引起明显的炎症反应与副作用。现将PG_s对眼压的调节作用和相关的调节机理及其治疗作用前景综述如下:     

环核苷酸与房水动力过程

小梁、睫状突供养血管和Schlemm管均有肾上腺素能神经分布。人眼睫状突、睫状体和虹膜的β受体各占虹膜睫状体β受体的1/3,小梁也有β受体分布。睫状上皮可能存在密度较高的多巴胺受体和ANP受体。正常房水中的肾上腺素,去甲肾上腺素、前列腺素、ANP和12(R)-HETE,可能是调节眼压的局部因素。cAMP和cGMP可能通过cAMP信号系统和IP_3-Ca~(2+)信号系统的相互作用,共同参与调节房水动力过程。依赖cAMP的蛋白激酶被激活后,能增强vimentin微丝等细胞骨架蛋白磷酸化,促进睫状体通道开放,调节房水分泌速率和流出易度。     

房水的葡萄膜巩膜排出通道

房水的葡萄膜巩膜排出通道是房水排出途径的重要组成部分，随着拟前列腺素药物在抗青光眼治疗中的应用，其临床重要性重新引起了人们的注意。对有关房水的葡萄膜巩膜排出通道的研究进行综述，重点介绍房水葡萄膜巩膜排出的测量技术和方法，正常值，生理学基础，药理学基础（主要包括胆碱能类药物、肾上腺素、前列腺素及其衍生物对房水葡萄膜巩膜排出的影响和机制）。     

人眼房水流通中Schlemm管的作用

房水以非常低的流速(2.0μl/min)经过房水通道。但是,这种低流量却能在一个很短的距离(<1mm)内产生很大的压力下降(pressuredrop)。正常眼压力下降约6mmHg左右。但是,青光眼压力下降可达40mmHg之多。为了更好地理解房水流出通道以及它与眼内压升高及青光眼的关系,作者研究了Sehlemm管在正常眼压力下降中的作用。许多研究着眼于证实房水通道中的流出阻力的主要部位。灌注试验表明随着眼压逐渐升高、房水流出阻力呈近于直线性变化。可能产生阻力的部位为:(1)角巩膜小梁网部;(2)邻管网部;(3)Schlemm管内壁的内皮细胞;(4)Schlemm管本身;(5)集合管和房水静脉。由于     

消炎痛与阿托品的散瞳协同作用

前列腺素(prostaglandins,PGs)参与眼外伤手术后的炎症反应,前列腺素E_1(PGE)_1在其中超重要作用。它使瞳孔缩小和房水蛋白渗出增加,给术中造成一定的困难,致术后一系列不良反应。尽管术前应用阿托品和肾上腺素等药能使瞳孔散大,但往往不能达到理想的要求。据报导,消炎痛能通过抑制PGs合成而抑     

水通道蛋白1与房水的产生及排出的关系

目的研究水通道蛋白(AQP1)在房水的产生、排出及调节机制中的作用.方法运用免疫组织化学法测定人眼房水的产生及排出通路相关组织中AQP1的表达.结果在睫状体非色素上皮、小梁网内皮细胞、Schlemm's管内皮细胞及虹膜基质中有AQP1的表达.结论证实了AQP1在房水的产生及排出通路组织细胞中的表达,为房水的正常代谢及青光眼发病机制的研究提供了分子生物学基础.     

前列腺素衍生物类药物降眼压的作用机制

病理性眼压升高是青光眼主要的危险因素,目前针对青光眼的手术及药物治疗都旨在降低眼压.前列腺素衍生物因具有降眼压作用而成为治疗青光眼的首选药物.现有的研究表明,前列腺素衍生物类药物主要是通过增加房水从葡萄膜巩膜通道外流来降低眼压的,最新的研究发现贝美前列腺素还可以通过增加房水从小梁网通道外流来降低眼压.目前关于前列腺素衍生物类药物降眼压作用机制仍然在不断地了解、观察、研究中.     

水通道蛋白l与房水的产生及排出的关系

目的 研究水通道蛋白(AQPI)在房水的产生、排出及调节机制中的作用。方法 运用免疫组织化学法测定人眼房水的产生及排出通路相关组织中AQPl的表达。结果 在睫状体非色素上皮、小梁网内皮细胞、Schlemm‘‘‘‘s管内皮细胞及虹膜基质中有AQPl的表达。结论 证实了AQPI在房水的产生及排出通路组织细胞中的表达，为房水的正常代谢及青光眼发病机制的研究提供了分子生物学基础。     

前列腺素治疗青光眼研究的新进展

前列腺素(PG)早期一直被认为是眼内刺激性炎症反应的媒介。直至1977年,局部小剂量应用被发现具有良好的降低眼压的作用,其后大量的动物实验和临床试用证实了有多种前列腺素具有良好的降眼压作用,其中以PGF_2。效果为佳。房水动力学的研究也揭示了PG降眼压的部分机理。研究结果显示了前列腺素适用于青光眼治疗,也是青光眼药物治疗中重大发展之一。     

Aqueous flow through the iris-lens channel: estimates of differential pressure between the anterior and posterior chambers

PURPOSE: To explore the hypothesis that differential pressure between the anterior and posterior chambers arises from the dynamics of aqueous flow across the iris-lens channel. METHODS: Navier-Stokes equations of fluid dynamics were derived and evaluated numerically for a viscous homogeneous isotropic fluid (aqueous) passing through the iris-lens channel, which is a spherical disc-shaped region conforming to the lens curvature while maintaining a separation distance (channel height) over a certain disc width (channel length). The effect of iridotomy was assessed using Poiseuille flow dynamics. RESULTS: In the absence of measured values, ranges of anatomic and physiological variables were used for calculations. The magnitude of the posterior to anterior pressure difference was greater with increases in channel length or aqueous flow and with decreases in channel height or pupil diameter. With a nominal channel length of 0.5 mm, aqueous outflow of 2.2 microl/min, and pupil diameter of 1 mm, the pressure difference increased from 0.9 to 10 mm Hg when the channel height decreased from 7 to 3 microm. A channel height of 10 microm or greater reduced the pressure difference below 1 mm Hg for the full range of other channel parameters considered. A 50-microm iridotomy reduced the pressure difference below 1 mm Hg. CONCLUSIONS: The flow of aqueous through the iris-lens channel is driven by the pressure differential between the posterior and anterior chambers. Viscous forces within the aqueous govern the magnitudes of the flow resistance and the pressure differential. The geometry and dimensions of a specific iris-lens channel will determine whether the pressure differential is of clinical significance.     

Effect of body position on intraocular pressure and aqueous flow

The relationship between intraocular pressure and the rate of aqueous humor formation was studied in human subjects. Intraocular pressure was altered by changing the subject's gravity-dependent body position. Aqueous humor flow was measured fluorophotometrically. An average change of intraocular pressure of 2.4 +/- 1.2 mmHg and 11.2 +/- 2.7 mmHg was recorded in subjects whose body position was alternated +/- 15 degrees from horizontal and +/- 50 degrees from horizontal. No change of the rate of fluorescein clearance was observed for the milder change of position. A small change of fluorescein clearance was noted in response to the steeper change of position. Changing intraocular pressure seems not to induce compensatory changes in aqueous flow. Therefore we conclude that aqueous formation is relatively pressure-insensitive, a conclusion one would draw from clinical instances of angle-closure glaucoma or as in other systems of secretion, such as the toad bladder or the cerebrospinal fluid, where alterations in pressure do not necessarily influence flow. If there is a regulator of aqueous flow it is not responsive to the changes in intraocular pressure brought about in this study. If aqueous flow regulates intraocular pressure or compensates for changes in intraocular pressure, the signal is not small changes in pressure.     

Correlation of aqueous humor ascorbate with intraocular pressure and outflow facility in hereditary buphthalmic rabbits

The hypotensive effect of ascorbate on intraocular pressure has been reported following topical application, oral administration, or anterior chamber infusion in animals. The present report describes the correlation of aqueous humor ascorbate concentration with intraocular pressure as well as outflow facility in vivo. Low aqueous ascorbate level was seen in buphthalmic eyes with high intraocular pressure and low outflow facility. The opposite correlation was observed in normal eyes. Ascorbate concentration in the anterior chamber of the rabbit eye is apparently related to the alteration of outflow facility and the movement of fluid in the anterior chamber.     

Comparative evaluation of the tolerability of proxofelin and clofelin and their effects on the eye in patients with glaucoma

Tolerance and effects of proxofelin (1% proxodolole and 0.25% clofelin) and clofelin were compared in 39 patients (50 eyes) with primary open-angle glaucoma by open and double-blind methods. Intraocular pressure, ocular hydrodynamics, arterial pressure, and heart rate were examined before and on day 28 of treatment. The hypotensive effect of proxofelin was more expressed than that of clofelin, the drugs decreasing intraocular pressure by 37 and 27% of the initial value, respectively. Proxofelin decreased ophthalmic tone, significantly increasing the coefficient of fluid discharge easiness by 50% and decreasing the production of aqueous humor by 51.9%, while clofelin slightly (14%) increased the coefficient of fluid discharge easiness and decreased intraocular pressure mainly at the expense of suppressing aqueous humor secretion. Hence, the combined drug is preferable in comparison with the monopreparation. Moreover, proxofelin was well tolerated by the patients, which differs it favorably from clofelin.     

Use of triamcinolone acetonide particles to visualize aqueous outflow.

Using triamcinolone acetonide suspension within the anterior chamber allows visualization of fluid outflow for glaucoma surgeries where aqueous egress from the eye is desired for pressure control. Dilute non-preserved triamcinolone acetonide particles can be injected into the anterior chamber at the end of intraocular surgeries to assess fluid outflow and to provide an anti-inflammatory effect at the end-target tissue.     

The role of ciliary blood flow and ultrafiltration in aqueous humor formation

The purpose of this paper is to discuss the role played by transepithelial ultrafiltration in the formation of aqueous humor. Much of the discussion is based on published data. To give weight to conclusions some experiments were performed on rabbits, cats and monkeys. It is shown in rabbits that the normal difference in mean pressure between ciliary and femoral arteries of about 17 mmHg is reduced to about 12 mmHg when the animal is bled to a femoral arterial pressure of 50 mmHg. It is most likely, then, that in previous studies in monkeys ciliary arterial and mean hydrostatic capillary pressures were lowered to levels that precluded transepithelial ultrafiltration but with little effect on the rate of aqueous humor formation. Neostigmine at a dose of 3 μg/ml perfused through the anterior chamber is demonstrated to cause a transient increase in inflow of aqueous humor from the posterior chamber. No marked permanent change in aqueous humor formation was observed. Previous studies have shown that neostigmine causes pronounced vasodilatation in the ciliary processes. Thus, there is no obligatory positive correlation between ciliary blood flow and rate of aqueous humor formation.In rabbits and cats labeled albumin introduced into the anterior chamber does not pass, or passes very poorly, through the iris into the ciliary processes in vivo but in freshly killed animals labeled material enters the processes. The results demonstrate that there is no functional barrier between the anterior chamber and the ciliary processes. From data for permeability of iris-ciliary processes preparations and data for the albumin turnover in the tissue fluid of the ciliary processes it is possible to calculate an approximate value for the transepithelial difference in hydrostatic pressure. The value is less than the oncotic pressure of the tissue fluid. It is concluded that in rabbits transepithelial ultrafiltration is most unlikely to contribute positively to aqueous humor formation.     

Prostaglandins F2alpha and E2 in aqueous humor of patients with cataract surgery.

To understand the role of prostaglandins F(2alpha) and E(2) in aqueous humor under the normal condition, their concentrations were measured by enzyme immunoassay in aqueous fluid obtained from either eye of 60 patients during cataract surgery and correlated with clinical factors as the age and intraocular pressure. The concentrations of prostaglandin F(2alpha) in the aqueous of all patients were below the level of detection. The concentrations of prostaglandin E(2) in the aqueous were below the level of detection in 37 patients while ranged from 9 to 48 pg/mL (median, 31) in 23 patients. The levels of prostaglandin E(2) did not have correlation with the age of the patients or the intraocular pressure of the eyes. In conclusions, the concentrations of prostaglandin E(2) were apparently higher than the concentrations of prostaglandin F(2alpha) in the aqueous. This study could not prove the relationship between prostaglandin levels and the intraocular pressure or the age.     

Hydrodynamics of aqueous humor in chronic simple glaucoma : Mechanisms of pressure normalization by an artificial outflow system

To help elucidate the interplay of physical forces, in particular pressure and flow, controlling the distribution and absorption of aqueous humor in subconjunctival tissue, a recently published computational model was considered where the fluid production in the eye, its removal via the trabecular/uveoscleral pathways and a surgical pathway are taken into account. The target quantity is the intraocular pressure. The surgical outflow pathway is linked to a fluid bleb that is positioned below the subconjunctival tissue and is modeled as a porous medium. The computational study was conducted on the basis of the geometry and relevant parameters characterizing fluid production, the surgically formed fluid pathway as well as absorption by the subconjunctival vessels, the hydraulic and geometrical characteristics of the bleb and the outflow facility. Clinical observations can be physically interpreted on the basis of parametric studies.     

Corneal hydration and metabolically dependent transcellular passive transfer of water

A theoretical model of the fluid pump in the corneal endothelium of the rabbit is presented. It is proposed that the stromal and aqueous surfaces of the endothelial cells have different solute reflection coefficients and that an adequate solute concentration is maintained in the cells by a mechanism dependent on metabolic energy. The model does not require transendothelial active transport of either solute or water. However, it requires the net volume flow observed through the isolated endothelium from stroma to aqueous to occur across the cells. Two situations are possible: (1) that the osmolarity of the cells is lower than the aqueous solution in conjunction with the aqueous side of the cells having the larger reflection coefficient; (2) that the osmolarity of the cells is higher than that in the stromal solution in conjunction with the stromal side of the cells having the higher reflection coefficient. A consequence of these requirements is that in case 1 the hydrostatic pressure within the endothelial cell must be less than the hydrostatic pressure in the stromal solution. In case 2 the intracellular hydrostatic pressure must be greater than the hydrostatic pressure of the aqueous solution.In vivo when the eye is closed there is zero net volume flow across the endothelium. There will be an anteriorly directed volume flow through the intercellular channels equal in magnitude to the posteriorly directed flow across the cells. This will produce a circulation of volume flow across the endothelium.When the eye is opened evaporation will take place across the epithelium, resulting in a net volume flow from the aqueous fluid into the stromal fluid. While the volume flow through the intercellular channels should remain anteriorly directed, the volume flow across the endothelial cells may be either anteriorly or posteriorly directed, depending on the values of pressures, concentrations and reflection coefficients.Two independent theoretical estimates of the net volume flow across the isolated endothelium can be made and compared with experimental results. These estimates are 3·35 μl/hr/cm² and 2·56 μl/hr/cm². They are in good agreement with the average experimental value of 6·5 μl/hr/cm²(Maurice, 1972).     

Steroid-induced glaucoma after laser in situ keratomileusis associated with interface fluid

PURPOSE: To report the ocular manifestations and clinical course of eyes developing interface fluid after laser in situ keratomileusis (LASIK) surgery from a steroid-induced rise in intraocular pressure. DESIGN: Retrospective, noncomparative interventional case series. PARTICIPANTS/INTERVENTION: We examined six eyes of four patients who had diffuse lamellar keratitis develop after uneventful myopic LASIK surgery and were treated with topical corticosteroids. PRINCIPAL OUTCOME MEASURE: Slit-lamp findings, intraocular pressure measurements, and visual field loss. RESULTS: All eyes had a pocket of fluid develop in the lamellar interface between the flap and the stromal bed associated with a corticosteroid-induced rise in intraocular pressure. However, because of the interface fluid, intraocular pressure was normal or low by central corneal Goldmann applanation tonometry in all eyes. The elevated intraocular pressure was diagnosed by peripheral measurement in several cases after months of elevated pressure. All six eyes had visual field defects develop. Three eyes of two patients had severe glaucomatous optic neuropathy and decreased visual acuity develop as a result of undiagnosed steroid-induced elevated intraocular pressure. CONCLUSIONS: A steroid-induced rise in intraocular pressure after LASIK can cause transudation of aqueous fluid across the endothelium that collects in the flap interface. The interface fluid leads to inaccurately low central applanation tonometry measurements that obscure the diagnosis of steroid-induced glaucoma. Serious visual loss may result.