Reliable measurement of mouse intraocular pressure by a servo-null micropipette system.

PURPOSE. To develop a reliable technique for measuring intraocular pressure (IOP) in the mouse. METHODS. An electrophysiologic approach-the servo-null micropipette system (SNMS)-for measuring hydrostatic pressure was adapted for the mouse eye. Fine-tipped (5 microm in diameter) micropipettes were advanced across the cornea with a piezoelectric micromanipulator, and the IOP was continuously monitored for up to 46 minutes. RESULTS. The micropipette tip was visualized in the anterior chamber. With the SNMS, the IOP of black Swiss outbred mice under ketamine anesthesia was 17.8 +/- 0.4 mm Hg, higher than values previously estimated in inbred mouse strains by a larger bore microneedle manometric technique. After withdrawal of the micropipette, a second penetration led to a similar level of IOP. Hypotonic solutions increased and hypertonic solutions decreased IOP. Drugs that decrease inflow (acetazolamide, timolol) or increase outflow facility (pilocarpine, latanoprost) in primates and humans lowered steady state IOP in the mouse. The transient initial increase in IOP produced by pilocarpine reported in other animals was also observed in the mouse. Xylazine-ketamine anesthesia lowered IOP substantially in comparison with systemic anesthesia with either ketamine or tribromoethanol alone. CONCLUSIONS. The SNMS is the first reliable, reproducible method for measuring mouse IOP. The mouse IOP is sensitive not only to drugs known to reduce aqueous humor inflow but also to drugs that increase aqueous humor outflow facility in the eyes of primates and humans. The development of the SNMS is an enabling step in the use of the mouse for glaucoma research, including molecular genetics, molecular pharmacology, and the search for novel antiglaucoma drugs.     

青光安颗粒剂对自发性青光眼模型小鼠的降眼压作用及房水动力学的影响

背景 研究表明青光眼的眼压增高与转化生长因子-β(TGF-β)促进小梁网细胞外基质的堆积以及黏附分子CD44导致房水排出阻力增加有关.传统中药青光安颗粒剂是中医临床上常用的降眼压药物,其是否通过小梁网通路发挥作用尚不清楚.目的 研究青光安颗粒剂对自发性青光眼模型DBA/2J小鼠房水动力学的影响及其作用机制.方法 选取10只眼压正常的3月龄雌性DBA/2J小鼠作为对照组,采用计算机随机数字分配法将20只9月龄自发性眼压升高的DBA/2J小鼠随机分为高眼压组和青光安组,青光安组小鼠采用2.5 g/kg复方青光安颗粒剂灌胃,每天2次,连续15d,对照组和高眼压组小鼠以相同剂量生理盐水灌胃.采用经前房注入/抽吸系统进行眼压测量,分别以2.5、5.0 μl/min的速率继续灌注,计算房水流畅系数(C)值和房水流出阻力(R)值.将3月龄DBA/2J小鼠60只按计算机随机数字分配法分为高剂量青光安组、中剂量青光安组、低剂量青光安组和空白对照组,每组各15只,分别用25.00、12.50和6.25g/kg青光安颗粒剂灌胃,空白对照组用等容量生理盐水灌胃,给药后7d麻醉条件下提取各组小鼠含青光安药物血清和空白对照动物血清,然后收集各组小鼠含小梁网巩膜组织进行培养,采用纤连蛋白(FN)、层黏连蛋白(LN)和神经元特异性烯醇化酶(NSE)免疫组织化学染色鉴定小梁网细胞.终质量浓度为0、5、10、20、50和100 ng/ml的TGF-β处理小梁网细胞24h,采用MTT比色法检测各组细胞活性;用不同质量浓度含药血清培养经20 ng/mlTGF-β处理的小梁细胞,分别于培养后24、48和72 h采用ELISA法检测细胞上清液中TGF-β2受体质量浓度,采用Western blot法检测各组小梁网细胞中CD44蛋白的相对表达量.结果 对照组、高眼压组和青光安组小鼠在2.5 μl/min和5.0μl/min灌注速率下眼压明显不同,高眼压组小鼠眼压值明显高于青光安组和对照组,青光安组小鼠C值较高眼压组明显降低(1.08±0.36 vs.2.35±1.34),R值明显增加(1.05±0.47 vs.0.64±0.55),差异均有统计学意义(均P＜0.01).原代培养的细胞呈长梭形,FN、LN和NSE均呈阳性表达.5、10和20 ng/ml TGF-β处理组细胞活力值明显低于0 ng/ml TGF-β处理组细胞,差异均有统计学意义(均P＜0.05).与空白对照组比较,TGF-β组小梁网细胞上清液中TGF-β2受体质量浓度和细胞中CD44蛋白相对表达量均明显升高,差异均有统计学意义(均P＜0.01);细胞培养后24、48和72 h TGF-β+高剂量含药血清组细胞上清液中TGF-β2受体质量浓度和细胞中CD44相对表达量均明显低于TGF-β组和TGF-β+低剂量含药血清组,差异均有统计学意义(均P＜0.01).结论 青光安颗粒剂通过影响房水动力学因素达到降低青光眼眼压的作用.青光安含药血清能明显降低体外培养的鼠小梁网细胞中TGF-β2受体和CD44的表达.     

DBA/2J小鼠房水引流通道中色素颗粒分布及其与眼压关系的实验研究

目的 探讨色素性青光眼动物模型DBA/2J小鼠房水引流通道中色素颗粒形态、大小、数量与眼压之间的关系。设计实验研究。研究对象9周龄雄性DBA/2J小鼠20只(40眼)。方法 定期监测眼压和眼前节变化,12、20、28、36周龄随机各取3只(6眼),按眼压正常与否分成正常眼压和高眼压组。光镜观察不同眼压组房水引流通道结构及其内色素颗粒的分布。透射电镜观察前房和小梁网内色素颗粒的形态,用Image软件随机测量100个色素颗粒的直径,并比较不同眼压组小梁网内色素颗粒直径的差异。主要指标眼压,前房和小梁网内色素颗粒的直径。结果 DBA/2J小鼠从20周龄起出现虹膜色素颗粒脱失、播散,虹膜基质萎缩伴透照缺损。12和20周龄小鼠均未出现高眼压,28和36周龄分别有36.4%和75%的小鼠眼压升高。不同周龄间眼压差异有统计学意义(χ²=37.82,P<0.001)。与正常眼压组相比,高眼压组虹膜厚度变薄,前房内和虹膜前、后表面富含色素颗粒的细胞堆积,前房角变窄,小梁网内大量色素颗粒沉积。DBA/2J小鼠前房内色素颗粒的形状为圆形,平均直径(0.44±0.12μm);或椭圆...     

Cochlin deposits in the trabecular meshwork of the glaucomatous DBA/2J mouse

Cochlin deposits were observed in the trabecular meshwork (TM) of 8-month-old glaucomatous DBA/2J mice, coincident with the reported onset of increased intraocular pressure and optic nerve damage. An age-dependent increase in cochlin was observed up to 10 months of age and was paralleled by a decrease in type II collagen. Similar expression patterns exist in the TM of humans with primary open-angle glaucoma. Cochlin deposits, absent in non-glaucomatous mouse and human TM, may disrupt the TM extracellular matrix and obstruct aqueous humor circulation. Studies of DBA/2J mice offer promise for understanding the role cochlin may play in glaucoma.     

Studies on the circadian rhythm of IOP in rabbits: correlation with aqueous inflow and cAMP content

We investigated the relationship of aqueous humor inflow rate and cyclic AMP concentrations to the spontaneous and dramatic changes in IOP associated with onset of darkness in our previously described model of circadian rhythm of intraocular pressure. After onset of darkness, rabbits entrained in an environment with a daily alternating cycle of 12 hours light and 12 hours darkness (12L:12D) showed an 85% increase in outflow pressure, a nearly 60% increase in aqueous inflow rate and an 80% increase in aqueous cAMP. Animals desynchronized by an unpredictable light cycle showed no increase in IOP or inflow rate when measured at the same time intervals as were the entrained animals. Thus, the IOP, aqueous inflow rate and aqueous cAMP are all seen to change in the same direction in a pharmacologically unperturbed rabbit eye. Previous pharmacological studies in rabbits have correlated an increase in cAMP with a decrease in IOP and aqueous inflow.     

晚期青光眼的房水动力学变化

目的：观察晚期青光眼高眼压对睫状体功能的损害作用及对角膜透明性的影响。方法：应用扫描荧光光度计及Ｓｃｈｉｏｔｚ电子眼压计分别测定１５只正常眼和１５只晚期原发性青光眼眼压、房水排出率和房水流畅系数,并观察角膜的透明性。结果：晚期青光眼眼房水排出率显著下降,下降程度与眼压水平及病程成正比。房水排出率降低至０．８μｌ／ｍｉｎ。角膜出现水肿混浊,房水排出率下降愈甚,角膜透明性改变愈明显。结论：持续高眼压将     

Investigating the effect of ciliary body photodynamic therapy in a glaucoma mouse model

PURPOSE: To investigate the morphologic and functional effects of verteporfin ciliary body photodynamic therapy (PDT) in a murine glaucoma model and normal mouse eyes. METHODS: A glaucomatous mouse strain, DBA/2J and a normal control mouse strain (C57BL/6) were used in the study. Verteporfin was injected intravenously at doses of 1.0 (DBA/2J) or 2.0 or 4.0 (C57BL/6) mg/kg. Transscleral irradiation of the ciliary body was performed with light at a wavelength of 689 nm delivered through an optical fiber, with irradiance of 1800 mW/cm2 and fluence of 100 J/cm2. Laser irradiation was applied for 360 degrees of the corneoscleral limbus in C57BL/6 normal mice and for 180 degrees in DBA/2J mice. Retreatment was performed in C57BL/6 normal mice that had been treated with 2.0 mg/kg of verteporfin at post-PDT day 7. One eye of each animal was treated, and the fellow eye served as the control. The morphologic effect of PDT on the ocular structures was assessed by light and electron microscopy. The IOP was measured using an applanation tonometer with a fiber-optic pressure sensor. Surviving retinal ganglion cells (RGCs) in DBA/2J mice eyes were retrogradely labeled with a neurotracer dye at 12 weeks after PDT. RESULTS: In all groups, almost all ciliary body blood vessels in the treated area were thrombosed 1 day after PDT. In DBA/2J mice, ciliary epithelium and stroma were severely damaged 1 day after PDT. The mean IOP in treated eyes was significantly reduced compared with that in the control eyes in all groups. The reduction of mean IOP in DBA/2J mouse eyes persisted for 7 weeks, although the mean IOP in normal mouse eyes treated with 2 or 4.0 mg/kg verteporfin returned to the level of the fellow control eyes by 7 and 17 days after treatment, respectively. The mean number of RGCs in the DBA/2J treated eyes was significantly higher than in control eyes. CONCLUSIONS: Ciliary body PDT resulted in morphologic changes in the ciliary body, significant reduction of IOP, and prevention of ganglion cell loss in a mouse glaucoma model. These results suggest that ciliary body PDT is a more selective cyclodestructive technique with potential clinical application in the treatment of glaucoma.     

Neuronal nitric oxide synthase (nNOS) positive retinal amacrine cells are altered in the DBA/2NNia mouse, a murine model for angle-closure glaucoma

PURPOSE: To characterize retinal amacrine cell changes in eyes of DBA/2NNia (DBA) mice that develop an inherited angle-closure glaucoma. METHODS: DBA and non-glaucomatous C57BL/6J mice of different age groups (2 to 23 months of age) were studied and compared. Morphologic investigations included NADPH-diaphorase staining of retinal whole mounts and fluorescence immunohistochemistry of cryosections with antibodies against neuronal nitric oxide synthase (nNOS), tyrosin hydroxylase (TH), gamma aminobutyric acid (GABA), and vesicular acetylcholine transporter (VAChT). RESULTS: Immunohistochemistry of amacrine cell subpopulations in the retinae of DBA mice revealed no significant staining differences in the two mouse strains at all ages using antibodies against TH, GABA, and VAChT. However, staining with nNOS and NADPH diaphorase revealed significant differences between the DBA strain and the C57BL/6J mice. With the onset of elevated IOP and glaucoma beginning at around 6 months in the DBA mice, the total number of NOS positive amacrine cells continuously decreased from 1000 cells at 6 months of age down to 480 cells in animals older than 20 months of age, but did not decline in age-matched C57 mouse retinas. CONCLUSION: We previously described a parafoveal loss of nNOS positive amacrine cells in the monkey glaucoma model. The fact that there is also a significant decrease of nNOS amacrine cells in the glaucomatous mouse eye indicates a specific response of nNOS positive amacrine cells in glaucomatous retinopathy.     

青光眼动物模型DBA／2J小鼠的眼部特征及组织学观察

目的评价不同月龄DBA／2J小鼠的眼压、眼部特征及组织学变化。方法清洁级DBA／2J小鼠36只,3、5、7、9、11、14月龄各6只,3、9、14月龄的C57BL／6J小鼠各6只为对照。分别对实验鼠行眼前节照相,前房微管法眼压测量。用尼氏染色法对鼠视网膜切片进行染色并在光学显微镜下行视网膜神经节细胞（RGCs）计数,光学显微镜下对视网膜冰冻切片行视盘的形态学观察。结果鼠眼前节检查表明,DBA／2J小鼠从5月龄始逐渐发生虹膜色素播散、虹膜萎缩,虹膜透照可见瞳孔变形。眼压从7月龄开始升高,9月龄眼压升至高峰,14月龄降至对照组水平。各月龄DBA／2J小鼠眼压间的差异有统计学意义（F=27．600,P〈0．05）,各月龄C57BL／6J小鼠眼压间的差异无统计学意义（F=0．249,P=0．781）。DBA／2J鼠RGCs数量从7月龄开始减少,9～11月龄减少明显,各月龄DBA／2J鼠RGCs计数间的差异有统计学意义（F=23．594,P=0．000）,各月龄C57BL／6J小鼠RGCs计数的差异无统计学意义（F=1．816,P=0．211）。DBA／2J小鼠视盘凹陷于9～14月龄开始逐渐加深,而各月龄C57BL／6J小鼠的视盘形态无明显变化。结论随月龄的增长,DBA／2J小鼠眼前节病变逐渐加重,表现出继发性青光眼的相关形态学改变。DBA／2J小鼠是研究青光眼发病机制和视神经保护较好的动物模型。     

Effect of latanoprost on outflow facility in the mouse

PURPOSE: To assess the early effect of latanoprost on outflow facility and aqueous humor dynamics in the mouse. METHODS: Aqueous humor dynamics in NIH Swiss White mice were assessed with an injection and aspiration system, using fine glass microneedles. A single 200-ng (4 microL) dose of latanoprost was applied to one eye 2 hours before measurement. The fellow eye served as a control. Intraocular pressure (IOP) was measured by using an established microneedle procedure. Outflow facility (C) was determined by constant-pressure perfusion measurements obtained at two different IOPs. Aqueous humor flow (Fa) was determined by a dilution method using rhodamine-dextran. Conventional and uveoscleral outflow (Fc and Fu) were calculated by the Goldmann equation. RESULTS: Average IOP, Fa, and C of control eyes were 15.7 +/- 1.0 mm Hg, 0.144 +/- 0.04 microL/min (mean +/- SD, n = 8), and 0.0053 +/- 0.0014 microL/min per mm Hg (n = 21), respectively. Average IOP, Fa, and C of treated eyes were 14.0 +/- 0.8 mm Hg, 0.138 +/- 0.04 microL/min (n = 8 for each), and 0.0074 +/- 0.0016 microL/min per mm Hg (n = 21), respectively. The differences between treated and control eyes were significant for IOP and total outflow facility only. CONCLUSIONS: These data indicate that the early hypotensive effect of latanoprost in the mouse eye is associated with a significant increase in total outflow facility. Alterations in the aqueous dynamics induced by latanoprost can be measured reproducibly in the mouse and may provide a useful model for further determining the mechanism by which latanoprost reduces IOP and alters outflow facility.     

Aqueous humor dynamics in mice

PURPOSE: To assess aqueous humor dynamics in mouse eyes. METHODS: Aqueous humor dynamics of NIH Swiss White mouse were assessed with an injection and aspiration system, using fine glass microneedles. Intraocular pressure (IOP) was measured by a microneedle connected to a pressure transducer. Episcleral venous pressure (EVP) was measured by gradually lowering intracameral pressure until blood reflux into Schlemm's canal was observed. Outflow facility (C) was determined based on constant pressure perfusion measurements obtained at two different IOPs. Aqueous volume (V(a)) was determined by direct measurement of aspirated aqueous humor. Aqueous humor production (F(a)) was measured by the dilution method with rhodamine-dextran. Conventional and uveoscleral outflow (F(c) and F(u), respectively), as well as the turnover rate of aqueous humor, were also calculated. RESULTS: IOP and EVP were 15.7 +/- 2.0 and 9.5 +/- 1.2 mm Hg, respectively (n = 20). F(a) was 0.18 +/- 0.05 microL/min (mean +/- SD; n = 8). C was 0.0051 +/- 0.0006 microL/min per mm Hg (n = 8). Estimated F(c) and F(u) were 0.032 and 0.148 microL/min, respectively. F(c) was 18% of F(a). F(u) was 82% of F(a). V(a) was 5.9 +/- 0.5 microL (n = 8). The calculated turnover rate of aqueous humor was 2.5%. CONCLUSIONS: The mouse eye has similar aqueous production and aqueous humor turnover rate as the human eye. The presence of both conventional and uveoscleral outflow suggests that the mouse is a useful model system for further investigations of the biology of aqueous dynamics.     

Hsp27 phosphorylation in experimental glaucoma

PURPOSE: The role of heat shock proteins (Hsp) in injury response has been well established, but it is now becoming apparent that the phosphorylation state of Hsp27 may be a critical determinant of its ability to act in a protective capacity. In this study, the expression of Hsp27 and its phosphorylation were evaluated in an experimental glaucoma model in Brown Norway rats and in a spontaneous model of glaucoma in the DBA/2J mouse. METHODS: The intraocular pressure (IOP) of one eye was elevated by injecting 1.9 M saline into the episcleral vein, as previously described in Brown Norway rats. IOP was measured in awake Brown Norway rats before surgery and every other day after saline injection. After 10 days of elevated IOP, the retinas were either removed for Western blot analysis or fixed for immunohistochemistry (IHC). IOP measurement in 7-month-old female DBA/2J mice was performed by direct cannulation. Retinas of eyes with and without elevated IOP were collected for Western blot analysis. RESULTS: Western blot results showed a significant increase in total Hsp27 (3.9-fold; P < 0.05; n = 8) and phosphorylated Hsp27 (pHsp27) (2.1-fold; P < 0.05; n = 6) in high IOP eyes in the experimental rat glaucoma model, and similar increases were observed in DBA/2J mice with elevated IOP (3.1-fold and 2.2-fold for Hsp27 and pHsp27, respectively; P < 0.05; n = 5). In rats, increased Hsp27 and pHsp27 immunoreactivity were observed in the nerve fiber layer of elevated IOP eyes and colocalized with glial fibrillary acidic protein (GFAP) and with vimentin staining, suggesting that glial cells contribute to the increase in Hsp27 and pHsp27 seen in experimental glaucoma. No change in Hsp70 or Hsp90 was observed. CONCLUSIONS: These results confirm previous reports of elevated Hsp27 in experimental glaucoma and extend them to the DBA/2J mouse. In addition, a significant increase occurred in Hsp27 phosphorylation with elevated IOP in both models of glaucoma. IHC studies show that the increases in Hsp27 and pHsp27 occur primarily in glial cells.     

Aqueous humor inflow in normal and glaucomatous avian eyes

A new fluorometric method has been employed to measure inflow of aqueous humor (F) in normal and glaucomatous avian eyes. Most inflow determinations in previous studies have involved severe disturbance to the eye, or else F has been derived indirectly, as a function of outflow facility (C) or intraocular pressure (IOP). The procedure used in this study is readily accomplished, even with a large series of subjects, and F measurement involves no insult to the eye or extrapolations from parameters whose relationship to F is not fully understood. After inflow measurements had been completed, the same experimental animals were subjected to independent determinations of volume of the aqueous space, IOP, C, and several dimensional parameters, thus permitting a comprehensive assessment of aqueous fluid dynamics during eye development.     

Effects of a cyclic AMP phosphodiesterase inhibitor, 8'-pivaloyloxymethyl ester of griseolic acid, on aqueous humor dynamics in rabbits.

The mechanism by which pivaloyloxymethyl (POM) ester of griseolic acid (GA), a potent cyclic AMP-phosphodiesterase inhibitor, lowers intraocular pressure (IOP) in albino rabbits was studied. The rate of aqueous flow, measured by fluorophotometry, was significantly lower in GA POM ester-treated eyes (2.36 +/- 0.24 microliters/min) than in control eyes (3.02 +/- 0.24 microliters/min). Topically applied GA POM ester did not alter tonographic outflow or uveoscleral outflow. No differences in aqueous humor protein concentrations between GA POM ester-treated and control eyes were observed. It was thought that the GA POM ester lowered the IOP by decreasing the aqueous inflow. Topical application of this compound caused no inflammatory response in the eye or changes in the blood aqueous barrier.     

A study of the relation between intraocular pressure and aqueous humor flow in the pigment dispersion syndrome

Forty subjects with pigment dispersion syndrome with and without intraocular pressure (IOP) elevation were compared with 40 age-matched controls. Intraocular pressure, resistance to outflow, and the rate of flow of aqueous humor were compared. Eyes with higher IOP and higher resistance to outflow were found to have a normal rate of aqueous flow. The results are interpreted as demonstrating that moderate and chronic elevation of IOP in the adult human eye does not induce a chronic compensatory reduction of aqueous humor flow.     

Erythropoietin promotes survival of retinal ganglion cells in DBA/2J glaucoma mice

PURPOSE: Retinal ganglion cell (RGC) loss occurs in response to increased intraocular pressure (IOP) and/or retinal ischemia in glaucoma and leads to impairment of vision. This study was undertaken to test the efficacy of erythropoietin (EPO) in providing neuroprotection to RGCs in vivo. METHODS: The neuroprotective effects of EPO were studied in the DBA/2J mouse model of glaucoma. Mice were intraperitoneally injected with control substances or various doses of EPO, starting at the age of 6 months and continuing for an additional 2, 4, or 6 months. RGCs were labeled retrogradely by a gold tracer. IOP was measured with a microelectric-mechanical system, and EPO receptor (EPOR) expression was detected by immunohistochemistry. Axonal death in the optic nerve was quantified by para-phenylenediamine staining, and a complete blood count system was used to measure the number of erythrocytes. RESULTS: In DBA/2J mice, the average number of viable RGCs significantly decreased from 4 months to 10 months, with an inverse correlation between the number of dead optic nerve axons and viable RGCs. Treatment with EPO at doses of 3000, 6000, and 12,000 U/kg body weight per week all prevented significant RGC loss, compared with untreated DBA/2J control animals. EPO effects were similar to those of memantine, a known neuroprotective agent. IOP, in contrast, was unchanged by both EPO and memantine. Finally, EPOR was expressed in the RGC layer in both DBA/2J and C57BL/6J mice. CONCLUSIONS: EPO promoted RGC survival in DBA/2J glaucomatous mice without affecting IOP. These results suggest that EPO may be a potential therapeutic neuroprotectant in glaucoma.     

The effect of topical CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure and aqueous humor dynamics in rabbits

PURPOSE: To evaluate the ocular hypotensive effect of topical CS-088, an angiotensin AT1 receptor antagonist, and the effect of CS-088 on aqueous humor dynamics. METHODS: The effects of CS-088 on intraocular pressure (IOP) were studied in 2 models of rabbit ocular hypertension. Experimental ocular hypertension was induced in albino rabbits by injecting alpha-chymotrypsin into the anterior chamber (alpha-chymotrypsin rabbit). The effects of the single application of CS-088 were examined. Additionally, CS-088 was repeatedly administered over a period of 3 weeks to hereditary ocular hypertensive rabbits (buphthalmic rabbits, JWHR bu/bu) and the IOPs were monitored throughout the experiment. The effects of CS-088 on aqueous humor dynamics were also examined in normal rabbits. In this study, the methods of IOP recovery rate, two-level constant pressure perfusion and fluorescein-dextran perfusion were used respectively to determine the aqueous inflow, outflow facility and uveoscleral outflow (USF). RESULTS: CS-088 at 1% and 2% significantly lowered the IOP in the alpha-chymotrypsin rabbits with a maximum IOP reduction of 10.1 mmHg. The maximum effect obtained with 2% CS-088 was no greater than that with 1% CS-088. In the buphthalmic rabbits, 2% CS-088 also lowered IOP significantly. Timolol was effective in both models. In the study on aqueous humor dynamics, a slight increase in USF (17%) was seen after a topical application of CS-088 whereas changes in aqueous inflow or outflow facility were not observed. CONCLUSIONS: Topical CS-088 can decrease IOP in rabbits. Despite the USF change, the ocular hypotensive mechanism by CS-088 was not fully determined.     

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.     

The effect of betablockers with and without ISA on tonographic outflow facility

Summary The response of two ophthalmic betablockers, Timolol (without ISA) and Pindolol (with marked ISA), on IOP and tonographic outflow facility was investigated in a single-blind clinical study on 20 patients with glaucoma or ocular hypertension. In two treatment groups, ten patients each, in a randomized order IOP and tonographic outflow facility measurements were performed before and 2 hrs after drug application. Timolol reduced IOP by 6,8 mm Hg and Pindolol eye drops by 4,5 mm Hg. Both topically applied betablockers did not influence tonographic facility of outflow. It is concluded that the intrinsic sympathomimetic activity of an ophthalmic betablocker has no effect on outflow facility of aqueous humor.     

Schlemm管内皮细胞的生物力学对眼压的调节作用

目前关于房水如何流经Schlemm管(Schlemm's canal,sc)内壁以及内壁如何调节眼压的确切机制仍未阐明,但普遍认为房水会经过内壁上的大液泡和小孔进入SC.“漏斗效应”表明,绝大部分房水外流阻力位于SC内壁及其邻管组织,并通过大液泡和小孔进行调节.原发性开角型青光眼患者小孔形成受损,房水外流阻力增大,最终导致眼压增高.本综述旨在阐述SC内壁上的内皮细胞生物力学在房水外流阻力调节中发挥的作用.