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Purpose: The purpose of this study was to investigate risk factors for progression in the superior and inferior hemi-visual fields (hemi-VFs) and the corresponding hemi-disc/retinas in eyes with normal tension glaucoma (NTG)., Methods: A 5-year prospective follow-up of 90 patients with NTG with untreated intraocular pressure (IOP) consistently ≤ 15 mm Hg was conducted. The IOP and Humphrey Perimeter measurements and disc/retina stereo-photographs were taken every 3 and 6 months, respectively. Risk factors for progression in the superior and inferior hemi-VFs and in the superior and inferior hemi-disc/retinas were investigated., Results: The mean total deviation values decreased at -0.50 ± 0.76 and -0.13 ± 0.34 dB/year in the superior and inferior hemi-VFs, respectively (P < 0.001). In the superior hemi-VF, the risk factor for faster progression was greater long-term IOP fluctuation (P = 0.022). In the inferior hemi-VF, the risk factors were disc hemorrhage (DH), greater myopic refraction, body mass index (BMI), and vertical cup-to-disc ratio (v-C/D; P < 0.05). The progression probability was 47.7 ± 6.0 and 17.7 ± 4.7% at 5 years in the superior and inferior hemi-disc/retinas respectively (P < 0.001), and DH was a risk factor for progression in both (P = 0.001)., Conclusions: In NTG eyes, greater BMI, myopia, and v-C/D are characteristic risk factors for faster progression in the superior half of the optic nerve head (ONH), whereas long-term IOP fluctuation is the significant risk factor in the inferior half of the ONH, whereas DH is a risk factor in both., Translational Relevance: Different risk factors were identified in superior and inferior hemifields in NTG eyes.

Purpose: To estimate the prevalence of glaucoma and its risk factors in a Japanese community., Methods: This study included 3405 Japanese community dwellers who were ≥40 years of age and enrolled in the Hisayama Study. This population-based, cross-sectional study was conducted from 2017 to 2018. A glaucoma screening test was performed using stereo fundus images and swept-source optical coherence tomography. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria., Results: The prevalence of glaucoma was 7.6% (95% confidence interval [CI], 6.7-8.6) overall. The prevalence of primary open-angle glaucoma (POAG) was 5.8% (95% CI, 5.0-6.6); that of primary angle-closure glaucoma (PACG) was 0.7% (95% CI, 0.5-1.1); and that of exfoliation glaucoma was 1.1% (95% CI, 0.7-1.4). In addition to aging, lower estimated glomerular filtration rate (eGFR) (odds ratio [OR] = 1.15; 95% CI, 1.02-1.33), higher intraocular pressure (OR = 1.06; 95% CI, 1.01-1.12), longer axial length (OR = 1.44; 95% CI, 1.31-1.59), and thinner central corneal thickness (CCT) (OR = 1.09; 95% CI, 1.04-1.15) were significant risk factors for POAG. Diabetes (OR = 2.81; 95% CI, 1.19-6.62) was a significant risk factor for PACG, and diabetes (OR = 2.15; 95% CI, 1.03-4.47) and thinner CCT (OR = 1.14; 95% CI, 1.02-1.28) were significant risk factors for exfoliation glaucoma., Conclusions: The prevalence of glaucoma was approximately 8%, probably due to the increase in the Japanese aging population. Not only ocular factors but also lower eGFR for POAG and diabetes for PACG and exfoliation glaucoma were risk factors in a general Japanese population., Translational Relevance: Systemic factors such as eGFR and diabetes must also be considered when implementing preventive measures against glaucoma.

Purpose: To investigate the association between long-term regular exercise (exercise frequency and exercise time) and 5-year changes in intraocular pressure in a general Japanese population., Methods: This population-based, cohort study was conducted in 2007. A total of 3119 Japanese community dwellers aged ≥ 40 years underwent eye examinations including intraocular pressure measurement with a noncontact tonometer. Of these, 1871 subjects (801 men and 1070 women) who underwent intraocular pressure measurement in 2012 participated. We assessed the associations of exercise frequency and exercise time with intraocular pressure using a linear regression model, adjusted for age and possible risk factors that can affect intraocular pressure., Results: The mean 5-year intraocular pressure change ± standard deviation was - 0.84 ± 1.9 mmHg. After adjustment for age, sex, systolic blood pressure, diabetes, total cholesterol, high-density lipoprotein cholesterol, body mass index, waist circumference, smoking habit, alcohol intake, work intensity levels, and intraocular pressure at baseline, we observed that increased exercise frequency (times/week) and increased exercise time (min/week) were both significantly associated with reduced intraocular pressure (p < 0.05 each). In the subgroup analyses based on the presence/absence of possible confounding risk factors, there was no evidence of heterogeneity among all subgroups (p for heterogeneity > 0.2)., Conclusions: Increased exercise frequency levels and increased exercise time are both independently associated with reduced intraocular pressure levels after adjustment for confounding factors.

Purpose: To investigate the relationship between glucose tolerance levels and the circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in a general Japanese population., Design: Population-based, cross-sectional study., Methods: In 2012 and 2013, a total of 2809 Japanese community dwellers aged 40-79 years in the Hisayama Study underwent eye examinations including cpRNFLT measurement with spectral domain optical coherence tomography. Of these, 1324 subjects (578 men and 746 women) were enrolled. Glucose tolerance levels were determined by a 75-g oral glucose tolerance test. We conducted an analysis of covariance to estimate the mean values of cpRNFLT according to the subjects' glucose intolerance status., Results: The subjects with prediabetes or with diabetes mellitus had significantly lower age- and sex-adjusted mean cpRNFLT values than those with normal glucose tolerance (P = .04 and P = .0004, respectively). The age- and sex-adjusted mean values of cpRNFLT decreased significantly with elevating fasting plasma glucose and 2-hour postload glucose levels (all P for trend < .05). These associations were substantially unchanged after adjustment for potential confounding factors. The coexistence of poorer glucose tolerance and higher intraocular pressure levels was additively associated with thinner cpRNFLT., Conclusions: Our analyses revealed that poorer glucose tolerance was significantly associated with the reduction of cpRNFLT in a Japanese general population, suggesting that the loss of neural tissue in the eye begins at the prediabetic stage, and that hyperglycemia may play a role in the reduction of cpRNFLT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Ripasudil, a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, is a novel drug for glaucoma in Japan. ROCK inhibition not only reduces intraocular pressure (IOP) but also increases ocular blood flow. We investigated the effects of ripasudil on optic disc blood flow (ODBF) in rabbit eyes and in isolated rabbit ciliary arteries., Methods: We measured IOP by tonometry and ODBF by laser speckle flowgraphy (LSFG) in male Dutch rabbits. A single drop (20 μL) of 0.8% ripasudil was delivered to the ocular surface after topical application of phenylephrine hydrochloride to reduce the ODBF. The effects of ripasudil on isolated rabbit ciliary artery smooth muscle contractions were measured in vitro with a myograph., Results: Ripasudil inhibited the reduction of ODBF induced by phenylephrine at 30 and 120 min after instillation (P < .05). The blood flow change was not significantly correlated with the IOP change. Ripasudil induced a concentration-dependent relaxation in isolated rabbit ciliary arteries precontracted with a high-potassium solution. This relaxation was not mediated through the endothelium-dependent activities of nitric oxide synthase, prostacyclin, or the large-conductance calcium-activated K + channel as shown by the inability of specific inhibitors of these pathways to block the ripasudil-induced relaxation., Conclusions: Taken together, our results showed that ripasudil not only decreased IOP but also increased ODBF in rabbits. However, the changes in IOP were not correlated with the changes in ODBF. Ripasudil also induced a concentration-dependent relaxation of isolated rabbit ciliary arteries through a NO-independent mechanism. Further investigation of the effect of ripasudil on ODBF is needed.

We previously reported that elevated pressure induces axonal swelling and facilitates the synthesis of the neurosteroid, allopregnanolone (AlloP), in the ex vivo rat retina. Exogenously applied AlloP attenuates the axonal swelling, suggesting that the neurosteroid plays a neuroprotective role against glaucomatous pressure-induced injuries, although mechanisms underlying neurosteroidogenesis have not been clarified. The aim of this study was to determine whether AlloP synthesis involves activation of translocator protein 18 kD (TSPO) and whether TSPO modulates pressure-induced retinal injury. Ex vivo rat retinas were exposed to various pressures (10, 35, or 75 mmHg) for 24 h. Expression of TSPO, 5α-reductase (5aRD), and AlloP was examined by quantitative real-time RT-PCR, ELISA, immunohistochemistry, and LC-MS/MS. We also examined the effects of TSPO ligands on AlloP synthesis and retinal damage. In this acute model, quantitative real-time RT-PCR and ELISA analyses revealed that elevated pressure facilitated TSPO expression. Similarly, these methods also detected enhanced 5aRD (mostly type II), which was observed in retinal ganglion cells (RGC) and the inner nuclear layer (INL). Atriol, a TSPO antagonist, suppressed pressure mediated AlloP synthesis and induced more severe histological changes in the inner retina when combined with elevated pressure. PK11195, a TSPO ligand that facilitates AlloP synthesis by itself, remarkably diminished pressure-mediated retinal degeneration. These results suggest that AlloP synthesis is induced by sequential activation of TSPO and 5aRD in an ex vivo glaucoma model, and that TSPO agonists may serve as potential therapeutic agents for the prevention of pressure-induced retinal damage., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Ｗe conducted a survey to evaluate the current status of glaucoma-related medical data management and standardization, aiming to improve the development of glaucoma care and research in Japan. Materials and methods: The survey was performed as a paper-based questionnaire of 14 universities that both participate in the glaucoma-related data standardization committee, established by the Japan Glaucoma Society in 2014, and actively perform glaucoma care. Results: All enrolled university hospitals installed an electronic hospital information system and used any of three ophthalmology-limited electronic chart systems. However, only 30.8% of the hospitals established a data extraction system from an electronic medical chart system, and only 14.3% could practically apply medical data for secondary research purposes. In all, 35.7% of the hospitals operate a medical cooperation system with local medical institutions and 42.9% electronically managed medical data inside their departments. Conclusion: This survey clarified the current state of medical data management and standardization.

A wide variety of animal models have been used to study glaucoma. Although these models provide valuable information about the disease, there is still no ideal model for studying glaucoma due to its complex pathogenesis. Animal models for glaucoma are pivotal for clarifying glaucoma etiology and for developing novel therapeutic strategies to halt disease progression. In this review paper, we summarize some of the major findings obtained in various glaucoma models and examine the strengths and limitations of these models.

Purpose: Allopregnanolone is a neurosteroid and powerful modulator of neuronal excitability. The neuroprotective effects of allopregnanolone involve potentiation of γ-aminobutyric acid (GABA) inhibitory responses. Although glutamate excitotoxicity contributes to ganglion cell death in glaucoma, the role of GABA in glaucoma remains uncertain. The aim of this study was to determine whether allopregnanolone synthesis is induced by high pressure in the retina and whether allopregnanolone modulates pressure-mediated toxicity., Methods: Ex vivo rat retinas were exposed to hydrostatic pressure (10, 35, and 75 mm Hg) for 24 hours. Endogenous allopregnanolone production was determined by liquid chromatography and tandem mass spectrometry (LC-MS/MS) and immunochemistry. We also examined the effects of allopregnanolone, finasteride, and dutasteride (inhibitors of 5α-reductase), picrotoxin (a GABA(A) receptor antagonist), and D-2-amino-5-phosphonovalerate (APV, a broad-spectrum N-methyl-D-aspartate receptor [NMDAR] antagonist)., Results: Pressure loading at 75 mm Hg significantly increased allopregnanolone levels as measured by LC-MS/MS. Elevated hydrostatic pressure also increased neurosteroid immunofluorescence, especially in the ganglion cell layer and inner nuclear layers. Staining was negligible at lower pressures. Enhanced allopregnanolone levels and immunostaining were substantially blocked by finasteride, but more effectively inhibited by dutasteride and APV. Administration of exogenous allopregnanolone suppressed pressure-induced axonal swelling in a concentration-dependent manner, while picrotoxin overcame these neuroprotective effects., Conclusions: These results indicate that the synthesis of allopregnanolone is enhanced mainly via NMDARs in the pressure-loaded retina, and that allopregnanolone diminishes pressure-mediated retinal degeneration via GABAA receptors. Allopregnanolone and other related neurosteroids may serve as potential novel therapeutic targets for the prevention of pressure-induced retinal damage in glaucoma., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

In an ex vivo rat glaucoma model using dissected retinas, the neurosteroid allopregnanolone (AlloP) protects retinal ganglion cells (RGCs) via GABR/GABAA receptors. To determine the involvement of macroautophagy/autophagy in neuroprotection by AlloP, we examined the effects of autophagy activators, rapamycin and torin 2, and autophagy inhibitors, bafilomycin A1 and SAR405, on retinal retinal morphology and expression of MAP1 LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) and SQSTM1 (sequestosome 1). Administration of rapamycin or torin 2 exerted partial histological neuroprotection, while combined administration of AlloP with bafilomycin A1 or SAR405 induced severe degeneration in a hyperbaric condition. Electron microscopic analyses showed that the addition of AlloP significantly increased autophagosomes and degenerative autophagic vacuoles in the retinal nerve fiber layer. Immunoblotting showed that the addition of AlloP or autophagic activators increased the lipidated form of LC3B (LC3B-II) and suppressed SQSTM1. Moreover, bafilomycin A1 increased LC3B-II and SQSTM1 protein levels in the presence of AlloP without changes in corresponding mRNAs compared to AlloP-treated retinas in a hyperbaric condition. These data indicate that AlloP likely induces a protective form of autophagy in this model. In an in vivo rat model of glaucoma, we also observed neuroprotective effects of AlloP. Injection of polystyrene microbeads into the anterior chamber increased intraocular pressure about 3-fold and induced RGC apoptosis. A single intravitreal injection of AlloP or autophagy activators prevented apoptosis and protected RGCs with autophagy activation. We conclude that AlloP may serve as a potential therapeutic agent for the treatment of glaucoma via diverse mechanisms. Abbreviations: 2HBCD: 2-Hydroxypropyl)-β-cyclodextrin; 3-MA: 3-methyladenine; AlloP: allopregnanolone; AP: autophagosome; AVd: degradative autophagic vacuoles; GCL: ganglion cell layer; INL: inner nuclear layer; IOP: intraocular pressure; IPL: inner plexiform layer; LC3B-I: cytosolic form of LC3B; LCB-II: lipidated form of LC3B; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; mPTP: mitochondrial permeability transition pore; NDS: neuronal damage score; NFL: nerve fiber layer; OH: ocular hypertension; ON: optic nerve; ONL: outer nuclear layer; OPL: outer plexiform layer; p-STR: scotopic threshold response; RGC: retinal ganglion cells; RT-PCR: real-time reverse transcription polymerase chain reaction; SQSTM1: sequestosome 1; TUNEL: TdT-mediated dUTP Nick End Labeling [ABSTRACT FROM AUTHOR]

Purpose: The influence of myopia on glaucoma progression remains unknown, possibly because of the multifactorial nature of glaucoma and difficulty in assessing a solo contribution of myopia. The purpose of this study is to investigate the association of myopia with visual field (VF) progression in glaucoma using a paired-eye design to minimize the influence of confounding systemic factors that are diverse among individuals. Methods: This retrospective study evaluated 144 eyes of 72 subjects with open-angle glaucoma, with similar intra-ocular pressure between paired eyes, spherical equivalent (SE) ≤ -2 diopter (D), and axial length ≥ 24 mm. Paired eyes with faster and slower VF progression were grouped separately, according to the global VF progression rate assessed by automated pointwise linear regression analysis. The SE, axial length, tilt ratio and torsion angle of optic discs, Bruch’s membrane (BM) opening area, and gamma zone parapapillary atrophy (PPA) width were compared between the two groups. Factors associated with faster VF progression were determined by logistic regression analysis. Results: The mean follow-up duration was 8.9 ± 4.4 years. The mean value of SE and axial length were -6.31 ± 1.88 D and 26.05 ± 1.12 mm, respectively. The mean global visual field progression rate was -0.32 ± 0.38 dB/y. Tilt ratio, BM opening area, and gamma zone PPA width were significantly greater in the eyes with faster VF progression than those with slower progression. In multivariate analysis, these factors were significantly associated with faster VF progression (all P < 0.05), while SE and axial length were not associated with it. Conclusion: In myopic glaucoma subjects, tilt of the optic disc and temporal shifting and enlargement of the BM opening were associated with faster rate of VF progression between paired eyes. This suggests that myopia influences VF progression in glaucomatous eyes via optic disc deformations rather than via refractive error itself. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association of myopia with the visual field (VF) defects in open-angle glaucoma (OAG) using paired eyes to eliminate the effect of unknown confounding factors that are diverse among individuals. Methods: One hundred eighteen eyes of 59 subjects with myopia (spherical equivalent [SE] ≥ -2 diopter [D] and axial length ≥ 24.0 mm) whose intra-ocular pressure between paired eyes was similar and the mean deviation (MD) of the Humphrey VF test differed by more than 6 dB were included. Refractive errors (SE, axial length) and parameters associated with the papillary and parapapillary myopic deformation (tilt ratio, torsion angle, and β-zone parapapillary atrophy [PPA] area without Bruch’s membrane) were measured in each eye. The paired eyes were divided into worse and better eyes according to the MD of the VF, and parameters were compared between them. Further, multiple linear regression analysis was performed to examine the correlation of the difference in various parameters with the MD difference between paired eyes. Results: The SE of all eyes was -6.39 ± 2.15 D (mean ± standard deviation) and axial length was 26.42 ± 1.07 mm. MD of the worse and better VF eyes were -13.56 ± 6.65 dB and -4.87 ± 5.32 dB, respectively. Eyes with worse VFs had significantly greater SE, axial length, tilt ratio, and PPA area without Bruch’s membrane than those with better VFs (all P < 0.05). In multiple linear regression analysis, the difference of the MD between paired eyes was significantly correlated with the difference in the tilt ratio and PPA area without Bruch’s membrane. Conclusion: The myopic papillary and parapapillary deformations, but not refractive error itself, were related to the worse VF in paired eyes with OAG. This suggests that myopia influences the severity of the glaucomatous VF defects via structural deformation. [ABSTRACT FROM AUTHOR]

Purpose: In normotensive eyes, reduced ocular blood flow can lead to glaucoma pathogenesis. Drugs that reduce intraocular pressure (IOP) often cause vasodilation of the ciliary arteries and improve blood flow to the eye. A novel class of drugs called Rho-associated coiled coil-forming protein kinase (ROCK) inhibitors can lower IOP. Therefore, we tested the ability of two ROCK inhibitors, Y-27632 and Y39983, to relax rabbit ciliary arteries. Methods: We measured in vitro ciliary artery smooth muscle contractions by isometric tension recordings and changes of intracellular free calcium concentration ([Ca]) by fluorescence photometry. Results: Both Y-27632 and Y-39983 induced a concentration-dependent relaxation in rabbit ciliary arteries precontracted with a high-potassium (high-K) solution. The amplitude of relaxation induced by Y-27632 and Y-39983 was not affected by either 100 μM N-nitro- l-arginine methyl ester ( l-NAME) or 10 μM indomethacin. In Ca-free solution, Y-27632 and Y-39983 significantly inhibited the transient contraction of ciliary arteries induced by 10 μM histamine. However, neither Y-27632 nor Y-39983 affected the elevation of [Ca] induced by high-K solution and histamine. Conclusions: We concluded that Y-27632 and Y-39983 relaxed isolated rabbit ciliary artery segments in vitro. The mechanism of relaxation was not dependent on endothelial-derived factors such as nitric oxide (NO) or prostacyclin, nor was it dependent on changes in intracellular Ca concentration. [ABSTRACT FROM AUTHOR]

Purpose. To clarify the vasodilator mechanism of unoprostone isopropyl (unoprostone), a PG F2α related compound used for treatment of glaucoma, we have investigated the effect of this drug and its metabolites on isolated rabbit ciliary artery in vitro. Methods. Under the dissecting microscope, ciliary arteries were prepared from albino rabbit eyes and mounted in a mayo-graph system. The effects of unoprostone isopropyl and other agents were investigated using isometric tension recording methods. Results. Unoprostone induced a dose-dependent relaxation in ciliary arteries that were pre-contracted with high-K solution, 10μM histamine or 10μM PG F2α. Neither unoprostone metabolite M1 or M2 had a relaxant effect on the reconstructed vessels. Relaxation was unaffected by inhibition of ardently cycles with SQ 22536, guanylyl cyclase with ODQ, or maxi-K channels with iberiotoxin. Pretreatment with unoprostone did not affect histamine-induced transient contractions in Ca2+ -free solution. However. SKF9365. a general Ca2+ channel blocker. evoked relaxation similar to unoprostone with respect to amplitude and rate of onset. Conclusions. Unoprostone, but not its metabolites M1 and M2, relaxed pre-contracted rabbit ciliary artery. The mechanism of vascular smooth muscle relaxation by unoprostone differs from that of IOP reduction and does not depend on adenylyl cyclase, guanylyl cyclase, or maxi-K channels. Relaxation may be mediated by inhibition of Ca2+ entry, possibly through capacitative Ca2+ channels. [ABSTRACT FROM AUTHOR]

Purpose To investigate characteristics of lamina cribrosa (LC) defects in myopic eyes with open-angle glaucoma (OAG) using spectral-domain (SD) optical coherence tomography (OCT). Design Cross-sectional study. Participants One hundred thirty-three eyes with OAG and 83 eyes without OAG, with axial length of 24 mm or more. Methods Serial enhanced depth imaging SD OCT B-scans of the optic disc were acquired and reviewed for LC defects (diameter, ≥100 μm) and large pores (diameter, 60–100 μm). The numbers and locations of LC defects and large pores in each eye were assessed. In eyes with OAG, factors related to the number of LC defects were evaluated, as well as the association between the locations of LC defects and visual field (VF) defects (e.g., paracentral scotoma [PCS] and superior or inferior hemifield defects). Main Outcome Measures Numbers and locations of LC defects and large pores. Results In myopic eyes with and without OAG, the average numbers of LC defects were 3.8 and 0.8 and numbers of large pores were 1.9 and 1.6, respectively. In both groups, LC defects and large pores were located predominantly at the temporal periphery. Among eyes with OAG, the number of LC defects was relatively high in the eyes with greater optic disc tilt angle and worse mean deviation of the VF (both P < 0.001). The number of temporal LC defects and tilt angle were associated with presence of PCS, whereas the number of inferior and superior LC defects and torsion direction were associated with presence of superior and inferior VF defects. Conclusions Myopic eyes with OAG exhibited LC defects and large pores at similar locations as those without OAG, but in greater numbers, suggesting that these focal alternations of the LC in myopic eyes may evolve into larger defects when glaucoma develops in the eye. The number of LC defects, which was related to the optic disc tilt angle, was associated significantly with glaucomatous VF defects in both severity and location. This suggests that myopia may influence glaucomatous VF defects through optic disc tilt by way of an increased number of LC defects at the temporal periphery. [ABSTRACT FROM AUTHOR]

Abstract: Our objective was to determine if tafluprost, a newly synthesized antiglaucoma drug, can relax precontracted rabbit ciliary arteries, and if so, to elucidate the underlying mechanism. We used isometric tension recordings of smooth muscle contractions and fluorescence photometry to monitor the change of intracellular free calcium concentration ([Ca2+]i) in isolated rabbit ciliary artery segments. Tafluprost induced a concentration-dependent relaxation in rabbit ciliary arteries precontracted with a high-K solution. The amplitude of relaxation induced by tafluprost was unchanged by 100μM l-NAME, 10μM indomethacin, denudation of vascular endothelium, 30μM thapsigargin, or 100μM ouabain. In Ca2+-free solution, 30μM tafluprost did not decrease the amplitude of contraction induced by 1μM histamine or the amplitude of the [Ca2+]i increase induced by 10μM histamine. The mechanism of tafluprost-induced relaxation was different from diltiazem, a voltage-dependent Ca2+ channel blocker. However, in thapsigargin-pretreated preparations incubated in Ca2+-free solution, tafluprost attenuated the capacitative increase of [Ca2+]i upon Ca2+ reintroduction to the extracellular medium. Thus, we conclude that tafluprost relaxed isolated rabbit ciliary artery segments precontracted with a high-K solution. The relaxing mechanism was not dependent on endothelial-derived factors, and not affected by the intracellular Ca2+ cycles or the Ca2+ extrusion component of the extracellular Ca2+ cycles. Relaxation of rabbit ciliary artery smooth muscle by tafluprost may be due, at least in part, to inhibition of capacitative Ca2+ entry from the extracellular space. [Copyright &y& Elsevier]