Localisation of prostaglandin F2 alpha and E2 binding sites in the human eye.

Prostaglandin F2 alpha reduces intraocular pressure possibly by increasing uveoscleral outflow. To further understand the mechanism of its action binding sites for prostaglandin F2 alpha and, for comparison, prostaglandin E2 were localised in sections of human cadaveric eyes using an in vitro ligand-binding technique and autoradiography. Specific binding sites for both prostaglandin F2 alpha and E2 were co-localised at a high level in the areas of the ciliary muscles and iris sphincter muscles, and at a lower level in the iris epithelium and the retina. The results suggest that prostaglandin F2 alpha and also prostaglandin E2, could modulate uveoscleral outflow by binding to their receptors located on the ciliary muscles and inducing their relaxation.     

Isopropyl unoprostone increases the activities of matrix metalloproteinases in cultured monkey ciliary muscle cells

PURPOSE: The mechanism by which the prostaglandin F2alpha-related antiglaucoma compound isopropyl unoprostone (referred to as unoprostone) reduces intraocular pressure is largely unknown. Another prostaglandin F2alpha-related compound, latanoprost, influences the activities of matrix metalloproteinases in ciliary muscle. Unoprostone ophthalmic solution is metabolized to oxidized metabolites, mainly M1 and M2, in the eye. The aim of this study was to investigate whether intraocular metabolites of unoprostone, M1 and M2, change the metalloproteinase activity in cultured monkey ciliary muscle cells. MATERIALS AND METHODS: Monkey ciliary muscle cells and trabecular meshwork cells were grown separately to confluence in monolayer cell cultures. M1 (10 nM, 100 nM, or 1 microM), M2 (10 nM, 100 nM, or 1 microM), 100 nM prostaglandin F2alpha, or vehicle solutions were added to each culture medium for 48 hours. The media were then assayed to measure metalloproteinase activities quantitatively by means of substrate zymography. RESULTS: Compared with the vehicle controls, M1, M2, and prostaglandin F2alpha significantly increased the metalloproteinase-2 activity in cultured ciliary muscle cells in a dose-dependent manner, but did not affect the metalloproteinase-2 activity in cultured trabecular meshwork cells. All experimented prostaglandins slightly increased metalloproteinase-9 activity in ciliary muscle cells, although these changes were not significant. CONCLUSIONS: The current results show that unoprostone influences the metabolism of the extracellular matrix in the ciliary muscle and that remodeling of the extracellular matrix in the ciliary muscle may be a possible mechanism by which unoprostone ophthalmic solution reduces intraocular pressure.     

The EP2 receptor is the predominant prostanoid receptor in the human ciliary muscle.

Prostaglandins can reduce intraocular pressure by increasing uveoscleral outflow. We have previously demonstrated that the human ciliary muscle was a zone of concentration for binding sites (receptors) for prostaglandin F2 alpha and for prostaglandin E2. Here, we try to elucidate the types of prostanoid receptors in the ciliary muscle using competitive ligand binding studies in human eye sections and computer assisted autoradiographic densitometry. Saturation binding curves showed that the human ciliary muscle had a large number of binding sites with a high affinity for prostaglandin E2 compared with prostaglandin D2 and F2 alpha. The binding of tritiated prostaglandin E2 and F2 alpha in the ciliary muscle was displaced most effectively by prostaglandin E2 and 11-deoxy prostaglandin E1 (a selective EP2 prostanoid receptor agonist), whereas the binding of prostaglandin D2 was displaced most effectively by prostaglandin E2 and D2. These results indicate that the dominant prostanoid receptor in the human ciliary muscle is the EP2 subclass and that there is also a small number of DP receptors.     

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.     

Histologic findings in pigment dispersion syndrome and pigmentary glaucoma

PURPOSE: To investigate the morphologic changes in the trabecular meshwork in a case series of eyes with pigment dispersion syndrome and pigmentary glaucoma, and surgical trabeculectomy specimens from eyes with pigmentary glaucoma. MATERIALS AND METHODS: Trabecular meshworks from 6 whole eyes from 3 donors and 7 trabeculectomy specimens were studied by light and electron microscopy. Axonal counts from the whole eyes were correlated with qualitative and quantitative data of meshwork changes. RESULTS: Changes in the meshwork varied around the circumference of the eyes, but in all 6 eyes in most regions of the circumference there were numerous pigment granules within trabecular cells; pigment was not found within intertrabecular or cribriform spaces. In some regions of the circumference there was trabecular cell loss, loss of intertrabecular spaces, fusion of lamellae, and an increase in extracellular material under the inner wall of the canal. Separation of the normal tendinous connection to the canal wall cells was noted in some regions of all eyes. This change could be associated with regions of pathologic separation of the inner wall from the cribriform region, associated with partial obliteration of the lumen of the canal with cells and cell processes. In eyes with pronounced axon loss, meshworks showed most pronounced loss of trabecular cells and increased extracellular material. Trabeculectomy specimens had similar changes and, in addition, showed damaged trabecular cells and collapse of intertrabecular spaces without fusion of lamellae, consistent with artifacts from manipulation during surgery. CONCLUSIONS: Loss of trabecular cells, fusion of trabecular lamellae with collapse of intertrabecular spaces, increase in extracellular material, and obliteration of the canal were found in various amounts around the circumference of eyes with pigment dispersion syndrome and elevated intraocular pressure, and pigmentary glaucoma. These probably all contribute to the development of increased intraocular pressure. Meshworks from trabeculectomy specimens showed these findings and also showed artifactual damage of cells and loss of intertrabecular spaces. This suggests that handling during surgery may cause single trabeculectomy specimens to give only an incomplete picture of the pathophysiology of pigmentary glaucoma.     

Impact of prostaglandin-F(2alpha)-analogues and carbonic anhydrase inhibitors on central corneal thickness -- a cross-sectional study on 403 eyes

BACKGROUND: Histological changes of, in particular, collagen and extracellular matrix after administration of topical prostaglandin F(2alpha)(PGF (2alpha)) analogues have been reported. In view of this observation, we investigated the influence of PGF(2alpha) analogues on the central corneal thickness. PATIENTS AND METHODS: In a non-randomized, controlled, cross-sectional study, 403 eyes from 208 consecutive patients were examined: 149 eyes (normals/controls) and 79 with ocular hypertension (OHT), 119 eyes with primary open angle glaucoma (POAG) and 56 eyes with normal tension glaucoma (NTG). One experienced ophthalmologist measured the central corneal thickness (CCT) using ultrasound pachymetry (Tomey AL-2000, sequence of 5 measurements with an SD < 3 microm). The central corneal power was measured with the Zeiss keratometer. Depending on the topical treatment, the patients were classified into 4 groups: A) PGF(2alpha) analogues (n = 78), B) carbonic anhydrase inhibitors (n = 26), C) combination of PGF (2)(alpha) analogues and carbonic anhydrase inhibitors (n = 41), D) none of these drugs (n = 258). T tests and multiple linear regression analyses were used for statistical analysis. RESULTS: CCT was decreased significantly (p < 0.01 each) in eyes treated with PGF(2alpha) analogues (group A: 529 +/- 34 microM), in comparison with the untreated and non-glaucomatous eyes (part of group D: 542 +/- 35 microM, n = 148), untreated glaucomatous/OHT eyes (part of group D: 563 +/- 37 microM, n = 110), eyes treated with carbonic anhydrase inhibitors (group B: 561 +/- 32 microm) and eyes with a topical application of both PGF (2)(alpha) analogues and carbonic anhydrase inhibitors (group C: 555 +/- 48 microM. No correlation was found between CCT and diagnosis (OHT, POAG, NTG, control), gender, central corneal power, and intraocular pressure in a multivariate analysis. CONCLUSIONS: The present findings suggest that the topical application of prostaglandin F(2alpha) analogues onto the cornea reduces the central corneal thickness significantly. These changes might be attributed to effects of PGF(2alpha) analogues on the extracellular matrix of the corneal stroma via upregulation of matrix metalloproteinases. In clinical practice, corneal thinning under local PGF (2)(alpha) analogue treatment could result in underestimation of intraocular pressure levels as measured by applanation tonometry.     

Ocular and optic nerve blood flow at normal and increased intraocular pressures in monkeys (Macaca irus): a study with radioactively labelled microspheres including flow determinations in brain and some other tissues

The effects of moderate increments in the intraocular pressure on blood flow rates in the various tissues of the eye were studied in monkeys. Blood flow rates were determined with radioactively labelled microspheres, 15 μm in diam. One eye had its spontaneous intraocular pressure while the other eye had its pressure stabilized at a higher level. The mean values for the intraocular pressures in the two eyes were 13 and 41 cm H₂O respectively. In eyes with spontaneous intraocular pressure mean blood flow through the retina, the iris, the ciliary body, and the choroid were 25, 17, 89, and 607 mg/min respectively. Blood flow through the ciliary processes was 222 and through the ciliary muscle 153 g/min/00 g tissue respectively. In eyes with increased intraocular pressure there were statistically significant reductions in blood flow through the choroid and through the prelaminar part of the optic nerve by 29 and 30% of the mean blood flow through control eyes respectively. The changes in blood flow through the retina, the iris, the ciliary processes and the ciliary muscle were not statistically significant. They ranged from a reduction by 8% to an increase by 19% in eyes with increased intraocular pressure. The results suggest that even moderate increments in intraocular pressure cause clear reductions in the blood flow through the choroid and through the prelaminar part of the optic nerve, while blood flow through the retina outside the optic disc and through the different parts of the anterior uvea is efficiently autoregulated. It is suggested that the susceptibility of the optic disc to increments in intraocular pressure is due to the deficient autoregulation of blood flow through the optic disc, which in turn might be explained by the choroidal origin of the optic disc vessels which interferes with normal autoregulatory mechanisms.Determinations were also made of blood flow through various parts of the brain and some other organs. Two different doses of microspheres were used to determine blood flow rates in the brain and in the eye. The larger dose seemed to reduce blood flow by 25% or more in the brain and in the iris, while no such effect was seen in the retina, the choroid or the ciliary body.     

Morphological changes in the anterior eye segment after long-term treatment with different receptor selective prostaglandin agonists and a prostamide

PURPOSE. To investigate long-term changes in the anterior segment of primate eyes treated for one year with different prostaglandin agonists and a prostamide. The results were compared with those obtained after vehicle treatment and in untreated controls. METHODS. Sixteen young cynomolgus monkeys were unilaterally topically treated for 1 year with either bimatoprost 0.03% (prostamide), sulprostone 0.03% (EP(3)/EP(1) agonist), AH13205 0.1% (EP(2) agonist), or latanoprost 0.005% (FP agonist), which all lower IOP in this species at the doses applied. Four animals were treated with the vehicle only. In all cases the left eye was treated, the right eye remained untreated. Six monkeys served as untreated controls. Sections from 4 quadrants each of the circumference of the eyes of 16 drug-treated, 4 vehicle-treated and 6 untreated control animals were investigated qualitatively and quantitatively using light- and electronmicroscopy. The area of widened spaces between ciliary muscle bundles, the number of nerve fiber bundles at the muscle tips, and the width and length of the ciliary muscle were quantitated. RESULTS. The general morphology of the ciliary muscle and trabecular meshwork was normal in appearance and shape in all animals, whereas some localized morphologic changes were observed in the drug-treated animals. The changes were found to be similar in all four treatment groups. In the ciliary muscle, there was a significant increase in optically empty spaces between muscle bundles in the anterior portion of the longitudinal and the reticular ciliary muscle compared with untreated and vehicle-treated control animals. Within these spaces, significantly more myelinated nerve fiber bundles were found in drug-treated compared with normal control animals. Ultrastructurally the spaces were partly covered by endothelial-like cells which, in some areas, were in contact with the basement membrane of the microvasculature. In all treatment groups, there were also changes in the trabecular meshwork region. Significant regional differences among the different quadrants of the eyes and quantitative differences between treatment groups were observed. The ciliary epithelium had a normal appearance in all treatment groups. CONCLUSIONS. After one year of treatment with different prostaglandins and a prostamide, uveoscleral outflow pathways are enlarged and appear organized. Conventional outflow routes were also affected. Long-term treatment with AH13205, latanoprost, sulprostone, or bimatoprost also induces sprouting of nerve fibers.     

The HNK-1 epitope in the inner connective tissue layer of the human ciliary body in exfoliation syndrome and various types of glaucoma

Possible changes in the expression of the HNK-1 carbohydrate epitope in the inner connective tissue layer of the human ciliary body, located between the ciliary epithelium and muscle, was studied using 2 formalin-fixed, paraffin-embedded eyes with exfoliation syndrome, 33 eyes with different types of glaucoma, and 21 morphologically normal control eyes. A strong immunoreaction delineating cell processes was observed in this layer with monoclonal antibodies HNK-1 and VC1.1 recognizing the HNK-1 epitope in control specimens, whereas partly granular immunoreaction was present in eyes with exfoliation syndrome. Exfoliation material was also immunoreactive. In all types of advanced glaucoma, the immunoreaction was mostly granular in nature and greatly diminished. No difference in HNK-1 immunoreactivity between control and glaucoma eyes was seen in the retina and ciliary epithelium. Elevated intraocular pressure, either directly or by decreasing blood flow to the ciliary body, may cause degenerative or metabolic changes in the inner connective tissue layer cells that bear or secrete molecules sharing the HNK-1 epitope. The partly granular immunoreactivity in eyes with exfoliation syndrome only indicates changes in this epitope even without an increase in intraocular pressure.     

Reduction of intraocular pressure by topical administration of an inhibitor of the Rho-associated protein kinase

PURPOSE: Rho-associated coiled coil-forming protein kinase (ROCK) is a downstream target of a small GTPase, Rho. The kinase has been reported to regulate actomyosin-based contractility of smooth muscles by modulation of myosin phosphatase activity. Contractility of ciliary muscle could be implicated in regulation of intraocular pressure while that of ocular vessels could affect blood flow to retina. The present study has been performed to investigate the effect of a ROCK inhibitor on intraocular pressure in rabbits. METHODS: An inhibitor of ROCK, Y-27632, was dissolved in an ophthalmic solution and topically administered to the eye of a Japanese white rabbit. Intraocular pressure was measured by pneumatonography (n = 12, 24 eyes). Constriction of ciliary muscle was measured by the Magnus method using 12 eyes. RESULTS: Topical application of 0.1 and 0.03% Y-27632 significantly decreased the intraocular pressure, with maximum decreases of 5.3 and 4.3 mm Hg after 90 minutes compared with the control eye. Y-27632 inhibited the carbachol-induced constriction of rabbit ciliary muscle. CONCLUSIONS: The ROCK inhibitor reduced intraocular pressure in rabbits by topical instillation. The inhibitor relaxed the excised ciliary muscle which was previously constricted by carbachol suggesting that the inhibitor acts to increase the uveoscleral outflow. Our results suggest that the ROCK inhibitor is a promising treatment for glaucoma therapy in the next generation.     

Effects of prostaglandin E2 on intraocular pressure, anterior chamber depth and blood flow volume of the iris and the ciliary body in rabbit eyes]

The effects of prostaglandin E2 (PGE2) on intraocular pressure (IOP), anterior chamber depth, and blood flow volume of the iris and the ciliary body of albino rabbits were investigated. Swelling and marked capillary dilatation of the ciliary body were observed after topical application of PGE2. IOP increased immediately by 200 micrograms, 400 micrograms, and 1,000 micrograms of PGE2, reached a peak within 30 minutes; then decreased gradually. The anterior chamber depth decreased only at 5 and 10 minutes after 1,000 micrograms of PGE2. The blood flow volume of the iris and the ciliary body immediately increased, and kept it up for 3 hours. Changes of IOP may be associated with an increase of blood flow attendant upon capillary dilatation of the ciliary body, and an increase of aqueous outflow due to breakdown of the blood-aqueous barrier. In addition to morphological and functional changes of the ciliary body, further factors which promote vitreous volume expansion may play an essential part in the development of malignant glaucoma.     

Bimatoprost and prostaglandin F(2 alpha) selectively stimulate intracellular calcium signaling in different cat iris sphincter cells

Bimatoprost is a synthetic analog of prostaglandin F(2 alpha) ethanolamide (prostamide F(2 alpha)), and shares a pharmacological profile consistent with that of the prostamides. Like prostaglandin F(2 alpha) carboxylic acid, bimatoprost potently lowers intraocular pressure in dogs, primates and humans. In order to distinguish its mechanism of action from prostaglandin F(2 alpha), fluorescence confocal microscopy was used to examine the effects of bimatoprost, prostaglandin F(2 alpha) and 17-phenyl prostaglandin F(2 alpha) on calcium signaling in resident cells of digested cat iris sphincter, a tissue which exhibits contractile responses to both agonists. Constant superfusion conditions obviated effective conversion of bimatoprost. Serial challenge with 100 nM bimatoprost and prostaglandin F(2 alpha) consistently evoked responses in different cells within the same tissue preparation, whereas prostaglandin F(2 alpha) and 17-phenyl prostaglandin F(2 alpha) elicited signaling responses in the same cells. Bimatoprost-sensitive cells were consistently re-stimulated with bimatoprost only, and prostaglandin F(2 alpha) sensitive cells could only be re-stimulated with prostaglandin F(2 alpha). The selective stimulation of different cells in the same cat iris sphincter preparation by bimatoprost and prostaglandin F(2 alpha), along with the complete absence of observed instances in which the same cells respond to both agonists, strongly suggests the involvement of distinct receptors for prostaglandin F(2 alpha) and bimatoprost. Further, prostaglandin F(2 alpha) but not bimatoprost potently stimulated calcium signaling in isolated human embryonic kidney cells stably transfected with the feline- and human-prostaglandin F(2 alpha) FP-receptor and in human dermal fibroblast cells, and only prostaglandin F(2 alpha) competed with radioligand binding in HEK-feFP cells. These studies provide further evidence for the existence of a bimatoprost-sensitive receptor that is distinct from any of the known prostaglandin receptor types.     

Uveoscleral outflow – A review

The uveoscleral outflow route was described more than 40 years ago. Part of aqueous leaves the eye through the iris root. The ciliary muscle, and there are large species differences in the fraction of aqueous outflow that leaves the eye through this route. In non-human primates 40–50% of aqueous leaves the eye by the uveoscleral route. In human eyes most data has been collected by indirect calculations, with results suggesting a similar fraction, at least in eyes from younger individuals. An age-dependent reduction in uveoscleral flow in human eyes may explain the initial difference seen between non-human primate and human eyes. Unlike trabecular outflow, intraocular pressures within the normal range have little effect on uveoscleral outflow. This may be explained by the fact that changes in intraocular pressure have little effect on the pressure gradient for flow through the ciliary muscle, which is likely to be the rate-limiting step in uveoscleral outflow. The state of the ciliary muscle is important and contraction reduces while relaxation increases uveoscleral flow. Similar effects are achieved with cholinergic agonists and antagonists. Epinephrine increases uveoscleral flow, most likely through stimulating β₂-adrenergic receptors. Prostaglandin F_2α and prostaglandin F_2α-analogues effectively reduce intraocular pressure by increasing uveoscleral flow. This is mediated by structural changes in the extracellular matrix of the ciliary muscle, and is likely to contribute to a valuable excess route for aqueous and proteins during intraocular inflammation. Whether uveoscleral flow plays a significant role in any other eye disease is not clear. Thus, 40 years later we are able to successfully increase aqueous flow through the uveoscleral route, a valuable contribution to glaucoma treatment, but we still have only a limited understanding on its physiological role.     

内窥镜激光睫状体光凝术后的组织病理学改变

目的:观察内窥镜下睫状体光凝术后组织的形态和病理变化,提出激光能量和手术路径的选择原则。方法:采用角巩缘切口和睫状体平部切口对用于角膜移植的10只供体眼(猝死后24 h内使用)行内窥镜下睫状体光凝术。比较两种操作的优缺点,不同激光能量水平下睫状突的反应,并对光凝区行组织病理检查。结果:内窥镜下睫状突清晰可见,激光能量小于0.3W时,组织没有反应,大于0.6W则组织爆裂,能量0.4-0.6W时,睫状突变白挛缩。两种手术入口均可顺利到达睫状体区并进行手术。术后睫状体的组织病理改变主要表现为有色素的睫状上皮细胞和睫状体基质的蛋白质变性,细胞结构破坏,组织排列紊乱、挛缩,而非色素上皮细胞则保持结构完好。结论:内窥镜下能直观、准确地完成睫状体激光光凝手术,术后睫状体基质和睫状突色素上皮的破坏是内窥镜激光睫状体光凝术降低眼压的主要原理。     

睫状环阻塞性青光眼的治疗方法的临床报道

目的探讨睫状环阻塞性青光眼的治疗方法及疗效。方法在本院行青光眼术后发生的睫状环阻塞性青光眼25例（27眼）,进行早期综合药物治疗,包括散瞳、皮质类固醇滴眼、碳酸酐酶抑制剂滴眼和口服,甘露醇静脉滴注等,疗程结束后所有患者均进行结果评定,并对其临床资料进行总结分析。结果术后早期均有轻度的角膜水肿,前房变浅或消失,眼压正常或升高。7眼青光眼联合白内障手术伴不同程度的前房渗出,2眼人工晶状体前膜形成,经皮质类固醇及散瞳局部治疗1周后角膜透明：渗出及膜均吸收,前房反应消失,前房深度恢复正常。此外,治疗后的平均眼压（17．3±2．3）mmHg,与治疗前平均眼压（25．0±2．0）mmHg比较,差异显著。结论早期综合药物治疗青光眼术后发生的睫状环阻塞性青光眼,眼压均得到有效的控制,治疗成功后部分患者继续长期滴用睫状肌麻痹剂的措施有一定效果。     

Prostaglandin E in rabbit aqueous humor after Nd-YAG laser photodisruption of iris and the effect of topical indomethacin pretreatment.

Ocular changes (prostaglandin E, protein, pupil diameter, and intraocular pressure) induced by photodisruption of pigmented rabbit iris with neodymium-yttrium aluminum garnet (Nd-YAG) laser and the effect of topical indomethacin upon those changes were examined. Concentrations of prostaglandin E in laser-treated eyes (1,3,5,10, and 20 lesions) were substantially greater than those in normal eyes and were associated with an initial hypertensive response. This finding was particularly striking in the case of 20 lesions. In that case, concentrations of prostaglandin E increased 50-fold, from 99 pg/ml of control level to 5049 pg/ml 60 min after irradiation. Disruption of blood aqueous barrier measured by protein concentration, changes in intraocular pressure, and pupil diameter occurred at a similar dose range of laser application. Concentration of protein and changes in pupil diameter already were prominent at 15 min after laser treatment, and changes in intraocular pressure were prominent at 60 min. Indomethacin pretreatment abolished most of these responses, suggesting that acute reactions following photodisruption largely depended on prostaglandin synthesis in iris tissue.     

F6H8前房内存留对眼内压影响的实验研究

目的:通过动物实验观察硅油清洗剂全氟己基正辛烷 (F6H8)存留于前房对眼内压的影响 ,探讨F6H8的安全性。方法 :新西兰白兔 15只 ,实验组 12只 ,对照组 3只 ,行前房穿刺术 ,注入F6H8(实验组 )或BSS (对照组 ) 0 15ml,术前后定期行裂隙灯检查、眼内压测量 ,并对小梁网组织行组织学检查。结果 :实验组眼压值比对照组升高明显。实验组内术后眼内压呈持续缓慢升高。组织学检查见术后 8周小梁网内皮细胞水肿变性 ,前房角有大量炎症细胞浸润。透射电镜下见小梁网细胞空泡样变性 ,巨噬细胞浸润。结论 :F6H8存留于前房 ,引起眼内压持续缓慢升高 ,8周时出现小梁网内皮细胞组织学结构改变。故临床上应尽量避免硅油清洗剂F6H8进入前房 ,已进入前房的F6H8要尽快取出     

Responses of intraocular pressure and the pupil of feline eyes to prostaglandin EP1 and FP receptor agonists.

PURPOSE: Previous studies suggested that FP receptors do not mediate the relaxation of the ciliary muscle and reduction of intraocular pressure in cats by prostaglandin (PG) F2alpha. The present study was undertaken to determine whether the reduction of intraocular pressure in cats induced by PGF2alpha is mediated by FP or other prostaglandin receptors. METHODS: One eye of each cat was treated topically with prostaglandin F2alpha, fluprostenol (FP receptor agonist), or 17-phenyl trinor PGE2 (EP1 receptor agonist) in a dose range of 12.5 to 50 microg. The effects of SC19220 and SC51089 (EP1 receptor antagonists), BWA868c, and SQ29548 (DP and TP receptor antagonists, respectively) on the intraocular response to PGF2alpha were also examined. At intervals up to 6 hours after treatment, intraocular pressure was measured with a pneumotonometer, and pupil diameters were measured with a millimeter ruler. RESULTS: In the dose ranges used, PGF2alpha and 17-phenyl trinor PGE2 decreased intraocular pressure and pupil diameter. The greatest reduction of intraocular pressure by 50.0 microg PGF2alpha was 5.0+/-1.4 mm Hg, whereas that by 50 microg 17-phenyl trinor PGE2 was 6.2+/-1.5 mm Hg. The isopropyl ester of PGF 2alpha at a dose of 1.25 microg reduced intraocular pressure by 3.75+/-0.25 mm Hg at 2 hours. At doses up to 100 microg, fluprostenol did not decrease intraocular pressure but did reduce pupil diameter. SC19220, a weak but selective EP1 receptor antagonist, inhibited the intraocular pressure response to both PGF2alpha and 17-phenyl trinor PGE2. The more potent EP1 receptor antagonist SC51089 had a greater inhibitory effect than SC19220 on the intraocular pressure response to PGF2alpha. Both of these antagonists had a small but non-dose dependent and statistically insignificant effect on the pupil response to PGF2alpha. These observations suggest that in cats, intraocular pressure and pupil responses to PGF2alpha, are mediated by EP1 and FP receptors, respectively. However, SC19220 significantly and dose-dependently inhibited the pupil response to 17-phenyl trinor PGE2alpha suggesting that EP1 receptors mediate pupil response to this agonist. DP and TP receptor antagonists at doses 5- to 20-fold greater than the IC50 values had no effect on the ocular hypotensive response to PGF2alpha. The concurrent administration of 12.5 microg of each of PGF2alpha and 17-phenyl trinor PGE2 did not produce an additive effect on intraocular pressure, indicating that in cats PGF2alpha and 17-phenyl trinor PGE2 act on the same receptor type. CONCLUSIONS: These results suggest that a significant proportion of the ocular hypotensive action of PGF2alpha in cats is mediated by EP1 but not by FP receptor. Evidence was also provided to show that 17-phenyl trinor PGE2 is an ocular hypotensive agent in cats.     

基质金属蛋白酶抑制剂抑制兔晶状体后囊膜混浊的研究

目的 观察基质金属蛋白酶(MMP)抑制剂对兔晶状体后囊膜混浊的抑制作用和对眼内组织的毒性.方法 实验研究.选用新西兰白兔行超声乳化晶状体吸除术,用不同浓度的MMP抑制剂GM6001溶液(实验1组:100 μmol/L,实验2组:200 μmol/L,实验3组:500 μmol/L)和GM6001阴性对照液(500 μmol/L)进行术毕及术后隔日晶状体囊袋内灌注3次,观察术后第12周内后囊膜混浊情况,同时观察药物对眼前房反应、眼压、角膜内皮、虹膜、睫状体和视网膜的影响和毒性.采用四格表确切概率法分析使用GM6001后前房反应和对后囊膜混浊的抑制作用;采用单因素方差分析法分析GM6001对眼压的影响.结果 裂隙灯显微镜下观察,可见术后12周对照组后囊膜混浊明显,实验1组后囊膜混浊较对照组轻,实验2组和3组均无后囊膜混浊(P=0.007);病理学结果显示:对照组和实验1组后囊膜表面有多层排列紊乱的上皮细胞和成纤维细胞,而实验2组和3组后囊膜表面几乎无细胞生长;前房反应轻:用药2 d实验组和对照组兔眼前房闪光情况比较,差异无统计学意义(P=0.380);对眼压的影响:实验组与对照组用药2 d(F=0.642,P=0.597)、7 d(F=0.179,P=0.909)眼压比较,差异均无统计学意义;用药7 d,实验3组角膜内皮细胞呈规则的六边形,无变形脱落,与对照组眼角膜内皮细胞形态无明显差别;光镜观察发现对虹膜、睫状体和视网膜均无明显毒性.结论 MMP抑制剂可明显抑制兔眼超声乳化晶状体吸除术后晶状体后囊膜混浊的发生,对眼内组织无明显毒性,安全有效.

Abstract：

Objective To determine whether matrix metalloproteinase (MMP) inhibitor can provide therapeutic effects for rabbits posterior capsule opacification in vivo and to observe the side effects of this drug on surrounding intraocular structures. Methods Experimental research. New Zealand white rabbits were undertaken phacoemulsification operation. GM6001 at different concentrations ( 100,200 and 500 μmol/L)and GM6001 negative control liqueur were infused into the capsule bags of the rabbits at the end of operation and two days after the operation. The incidence of posterior capsule opacification was assessed and the histological sections of posterior capsules were observed under microscope 12 weeks after the surgery. The anterior chamber response was observed on day 2 post-operatively. The changes of intraocular pressure were measured by day 2 and day 7. Corneal endothelial cells were observed under scanning electron microscopeand iris, ciliary body and retina were observed under microscope on day 7. Results GM6001 significantly prevented posterior capsule opacification (P=0. 007 ). No opacification occurred on the rabbit posterior capsule in eyes with 200 and 500μmol/L GM6001 on week 12 post-operatively in vivo. No cells were found on posterior capsule in 500 μmol/L group, whereas lens epithelial cells and fibroblasts were found in the controls under microscope. No difference of anterior chamber flare between the eyes with GM6001 at different concentrations and the control group (P=0. 380) by day 2 after the operation. The intraocular pressure in eyes with GM6001 was the same as that in the control 2-days ( F = 0. 642, P = 0. 597 ) and 7-days ( F =0. 179 ,P =0. 909) post-operation. The corneal endothelial cells in eyes with 500 μ mol/L GM6001 arranged regularly and did not show any difference from that in the control eyes under scanning electron microscope 7-day after the operation. The iris, ciliary body and retina in eyes with 500 μmol/L GM6001 were normal in appearance 7-day after the operation. Conclusions MMP inhibitor can prevent posterior capsule opacification effectively in rabbits in vivo and does not cause damage to surrounding intraocular structures,suggesting that MMP inhibitor may become a medication used for the prevention of lens posterior capsule opacification.     

Endolaser treatment of the ciliary body for uncontrolled glaucoma

We used vitrectomy and transvitreal endophotocoagulation of the ciliary processes to treat 18 eyes with severe glaucoma that could not be managed successfully by medical therapy and conventional glaucoma surgery. Lensectomy was performed in the two phakic eyes in the series because of cataractous lens changes. A pars plana vitrectomy was done in each eye and a fiberoptic probe used to apply transvitreal blue-green argon laser photocoagulation directly to the ciliary processes. Treatment of more than 180 degrees was necessary for sufficient lowering of the intraocular pressure. Postoperative intraocular pressure was equal to or less than 20 mmHg in 14 of 18 eyes, although nine of the 14 successful cases required postoperative medical therapy. Complications included transient vitreous hemorrhage (2 eyes), transient choroidal detachment (2 eyes), and hypotony (1 eye).