A PubMed Citations Search Study on the Prevalence of Epiphora in the General Adult Population.

PURPOSE: To assess the prevalence of epiphora in the general adult population based on PubMed search citations. METHODS: 1) Electronic PubMed MEDLINE database search (September 13, 2019) with the terms (Medical Subject Headings or MeSH) "prevalence" and "epiphora", 2) "epiphora" and "dry eye", and 3) "prevalence", "epiphora", and "dry eye". Review of all citations from these searches containing the term "epiphora" either in their abstract or title. RESULTS: 1) PubMed search retrieved 2 617 137 citations for "prevalence", 26 135 for "epiphora", and 2554 for "prevalence" AND "epiphora". Within the latter 2554 citations, the word "epiphora" appeared in the abstract or title of only 109 citations (< 5%). None of these 109 citations assessed the prevalence of epiphora in the adult general population as the primary end point. Only one abstract mentioned that out of 125 patients, 7.2% indicated, retrospectively, that they had already had epiphora before cataract surgery. Two large population-based studies addressed the incidence of epiphora, not in adults, but in infants (20%) and children (7.7%). 2) The PubMed search showed 22 487 citations for "dry eye", 30 211 for "epiphora" OR "dry eye", and up to 18 414 joint citations for the terms "epiphora" AND "dry eye". These 18 414 citations were 70 and 82% of the number of MeSH citations for "epiphora" and "dry eye" alone, respectively. Of these 18 414 citations, the word "epiphora" only appeared in 131 citations (< 1%), one of them being an extra report mentioning a 32% incidence of epiphora among postmenopausal women. 3) The search found 2206 citations for "prevalence" AND "epiphora" AND "dry eye", with only 10 of them (< 1%) containing the word "epiphora". CONCLUSIONS: Despite a large number of citations retrieved by PubMed searches, there seems to be a lack of studies on the prevalence of epiphora in the adult general population. There is apparently also a large number of overlapping PubMed citations retrieved for searches with the terms "epiphora" AND "dry eye", although more than 99% of them did not even display the word "epiphora". Although epiphora is considered a common complain, its prevalence in the adult general population deserves to be further assessed.

The influence of thalamosinusotomy under different constant intraocular pressures on aqueous outflow facility in isolated porcine eyes

OBJETIVO: Avaliar o efeito da thalamosinusotomia ab interno, que é um procedimento cirúrgico experimental similar a esclerotalamotomia ab interno, na drenagem do humor aquoso. MÉTODOS: Olhos de porco enucleados foram perfundidos com solução fisiológica de Krebs-Ringer e azul de tripan, sob diferentes pressões constantes de perfusão, após o procedimento cirúrgico experimental. A facilidade de drenagem e os tecidos corados/não corados foram medidos. RESULTADOS: A facilidade de drenagem e a área sob a curva (fluxo) aumentaram com o aumento do número de incisões da thalamosinusotomia (0 a 4). Olhos submetidos a thalamosinusotomia apresentaram mais tecido corado (conjuntiva, superfície externa e interna da esclera) que olhos submetidos a cirurgia sham, com diferença estatisticamente significativa (p< 0,05). CONCLUSÕES: Os resultados sugerem que a facilidade de drenagem aumenta com o aumento do número de thalamus, diferente vias de drenagem são estimuladas após a thalamosinusotomia, e a drenagem uveoscleral pode ser uma via importante após o procedimento cirúrgico experimental.

PURPOSE: To explorethe effect of the thalamosinusotomy ab interno, which is an experimental surgical procedure similar to sclerothalamotomy ab interno, on aqueous humor drainage. METHODS: Enucleated porcine eyes were perfused with Krebs-Ringer's physiologic solution and trypan blue, in vitro, under different constant pressures after the experimental procedure. The outflow facility and the stained/unstained tissue were measured. RESULTS: The outflow facility and the area under the curve (outflow) increased with the increasing number of thalamosinusotomy incisions (0 to 4). Thalamosinusotomy eyes showed more stained tissue (conjunctiva, outer sclera, inner sclera) than sham surgery eyes with significant statistical difference (P<0.05). CONCLUSIONS: The results suggested that outflow facility increases with the increasing number of thalamus, different pathways are stimulated after thalamosinusotomy, and the uveoscleral outflow could be an important route after the experimental surgical procedure.

Effect of cAMP on porcine ciliary transepithelial short-circuit current, sodium transport, and chloride transport.

PURPOSE: To investigate the effects of 8-bromo-cAMP (cAMP) on porcine ciliary transepithelial short-circuit current (Isc) and transport of chloride (Cl-) and sodium (Na+). METHODS: With Ussing-type chambers, cAMP-induced changes in Isc, electrical resistance (ER), and transepithelial 36Cl- and 22Na+ fluxes were measured. Drugs were applied to the nonpigmented epithelium (NPE) and/or pigmented epithelium (PE) side(s). The effect of IBMX (1, 5, or 10 microM; 3-isobutyl-1-methylxanthine) on Isc-increase induced by 8-bromo-cAMP on the PE side was also tested. RESULTS: On the NPE side, a single concentration (10 microM, 100 microM, or 1 mM) of 8-bromo-cAMP induced a biphasic (transient peak followed by sustained plateau) Isc increase. On the PE side, 8-bromo-cAMP induced a similar but delayed biphasic Isc increase at 1 mM, a slight plateau-Isc increase at 100 microM, and no Isc increase at 10 microM. In the concentration-response curve, the cAMP-induced peak-Isc increase became significant at a concentration 10,000 times lower on the NPE than on the PE side. At 10 microM, the cumulative cAMP-induced Isc-increase reached its maximum on the NPE side, but was virtually nonexistent on the PE side. IBMX (a phosphodiesterase inhibitor) but not 8-CPT-6-Phe-cAMP (higher permeability than 8-bromo-cAMP) significantly increased the peak-Isc concentration-response curve induced by 8-bromo-cAMP (10 nM-1 mM) on the PE side. On the NPE but not the PE side, 10 microM 8-bromo-cAMP induced a significant but transient increase in net PE-to-NPE 36Cl- flux (1.03 +/- 0.18 microEq/min per square centimeter; P < 0.001). Neither ER nor transepithelial 22Na+ flux was changed after cAMP exposure. CONCLUSIONS: In porcine ciliary processes, apparently on the NPE side, cAMP triggers a biphasic (transient peak followed by a sustained plateau) Isc increase. Only the peak-Isc increase involves an increase in net PE-to-NPE Cl- transport.

Vasoactive responses of U46619, PGF2alpha, latanoprost, and travoprost in isolated porcine ciliary arteries.

PURPOSE: To compare the vasoactive properties of the prostanoids U46619 (thromboxane A2 analogue), prostaglandin F(2alpha) (PGF(2alpha)), latanoprost free acid, and travoprost free acid in isolated porcine ciliary arteries. METHODS: In a myograph system (isometric force measurement), quiescent vessels were exposed (cumulatively) to U46619, PGF(2alpha), latanoprost, or travoprost (0.1 nM-0.1 mM). Experiments were also conducted in the presence of SQ 29548 (TP-receptor antagonist; 3-10 microM) or AL-8810 (FP-receptor antagonist; 3-30 microM). Contractions were expressed as the percentage of 100 mM potassium chloride-induced contractions. RESULTS: In quiescent vessels, contractions (concentration-response curves) induced by (0.1 mM) PGF(2alpha) (87.9% +/- 3.5%), U46619 (66.7% +/- 4.1%), and latanoprost (62.9% +/- 3.6%) were more pronounced (P < or = 0.001) than those induced by travoprost (23.0% +/- 4.4%). Concentration-response curves for PGF(2alpha), latanoprost, and travoprost were preceded by a smaller contraction peak (0.1 microM) that was higher (P < or = 0.05) for travoprost (24.4% +/- 2.8%) than for PGF(2alpha) (12.9% +/- 4.6%), but not different (P = 0.58) from latanoprost (22.0% +/- 3.0%). The 50% maximal contraction (PD50: negative log M concentration) of U46619 (-8.05 +/- 0.13) was lower (P < or = 0.001) than those of latanoprost (-5.65 +/- 0.10), PGF(2alpha) (-5.49 +/- 0.14), and travoprost (-5.12 +/- 0.52). Contractions were inhibited (P < or = 0.05-0.001) either by SQ 29548 or AL-8810. CONCLUSIONS: In isolated porcine ciliary arteries, all prostanoids tested induced contractions. Among them, travoprost appeared to be the least potent and U46619 the most efficient.

Role of anions in nitric oxide-induced short-circuit current increase in isolated porcine ciliary processes.

PURPOSE: To investigate how nitric oxide (NO) modulates short-circuit current (Isc) in isolated porcine ciliary processes. METHODS: Isc changes (Ussing-type chamber) induced either by the NO donors SNP or SIN-1, or by the cGMP analogue 8-pCPT-cGMP were assessed. The effect of inhibitors of guanylate cyclase (10 microM ODQ, 100 microM LY83583), protein kinase G (30 microM Rp-8-pCPT-cGMP, 3 microM KT 5823), protein kinase A (1 microM KT 5720), or protein kinase C (1 microM Go6983) on SNP- or 8-pCPT-cGMP-induced Isc changes were investigated. The effect of inhibitors of anion channel (100 microM niflumic acid, 1 mM DIDS, and 1 mM 9-AC), K+-channel (10 mM TEA, 10 mM BaCl2), Na+-channel blockers (1 mM amiloride), Na+-K+-2Cl- cotransporter inhibitor (0.5 mM bumetanide), or carbonic anhydrase inhibitor (1 mM acetazolamide) was studied. In Cl(-)- or HCO3(-)-free Krebs-Ringer solution, the effect of SNP- or 8-pCPT-cGMP-induced Isc changes was accessed. RESULTS: SNP, SIN-1, or 8-pCPT-cGMP increased Isc with a change in the potential difference that became more negative toward the nonpigmented epithelium (aqueous) side. The Isc increase induced by SNP or SIN-1, but not by 8-pCPT-cGMP, was prevented by ODQ and LY83583. SNP- and 8-pCPT-cGMP-induced Isc increases were prevented by Rp-8-pCPT-cGMP or KT5823 (but not by KT5720 or Go6983), or by niflumic acid, DIDS, 9-AC, or acetazolamide (but not by TEA, BaCl2, amiloride, or bumetanide). The effect of SNP and 8-pCPT-cGMP was abolished in Cl(-)- and reduced in HCO3(-)-free solutions. CONCLUSIONS: NO activates a guanylate cyclase-cGMP-protein kinase G pathway that appears to stimulate stroma-to-aqueous anionic transport, possibly Cl-, in porcine ciliary epithelium.

Increased expression of matrix metalloproteinases in mononuclear blood cells of normal-tension glaucoma patients.

PURPOSE: Glaucomatous optic neuropathy involves tissue remodeling by matrix metalloproteinases (MMPs). In this study we investigated MMP gene expression in circulating leukocytes isolated from normal tension glaucoma (NTG) patients in comparison to healthy controls. METHODS: Blood samples were collected from 6 glaucoma patients and 6 age- and sex-matched healthy controls. Leukocytes were separated using Ficoll-Hypaque gradient. mRNA pools were used for subtractive hybridization to identify genes with altered expression. The subtracted genes were sequenced and individual mRNA pools were quantified using semiquantitative RT-PCRs. Target PCR products were confirmed using sequence-based restriction analysis. In this study we focused on MMPs. RESULTS: MMP-9 and MT1-MMP (MMP-14) were subtracted as upregulated genes in the group of NTG patients. Upregulation of these genes was confirmed by RT-PCR and Western-blot analysis in all 6 patients. The expression of the tissue inhibitor of matrix metalloproteinases TIMP-1 was slightly enhanced in patients as compared with controls. Expression of MMP-2 was not detected in leukocytes either in glaucoma patients or in healthy subjects. CONCLUSION: A simultaneous upregulation of both MMP-9 and MT1-MMP gene expression and only slightly enhanced expression of TIMP-1 suggest an increased enzymatic matrix metalloproteinase activity delivered by mononuclear blood cells in these patients.

Adrenomedullin-induced endothelium-dependent relaxation in porcine ciliary arteries.

PURPOSE: To investigate adrenomedullin-induced relaxation in isolated porcine ciliary arteries. METHODS: In a myograph system (isometric force measurement), precontracted vessels ( approximately 0.1 micro M U46619; thromboxane A(2) analogue or approximately 10 nM endothelin-1) were exposed, in a cumulative manner, to increasing concentrations of adrenomedullin (1 nM to 1 micro M) in the presence or absence of different drugs. Some experiments were conducted in vessels with nonfunctional (intentionally mechanically damaged) endothelium. RESULTS: Adrenomedullin evoked marked relaxation [maximum relaxation (Rel(max)): 85.5 +/- 3.0%; negative log M concentration inducing 50% of Rel(max) (pD(2)): 7.4 +/- 0.1] in comparison to time-controls (Rel(max): 19.2 +/-4.8%; P < 0.001). Relaxation was inhibited by 3 micro M CGRP[8-37] (CGRP(1) receptor antagonist; Rel(max): 27.2% +/- 5.3%; P < 0.001) but not by 3 micro M adrenomedullin[22-52] (presumed adrenomedullin receptor antagonist; P = 0.75). Adrenomedullin-induced relaxation was less pronounced in nonfunctional endothelium vessels (Rel(max): 67.6% +/- 3.1%; pD(2): 6.9 +/- 0.1; P < 0.01). In vessels with functional endothelium, relaxation was not significantly influenced by 0.1 mM N(G)-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthesis inhibitor), 10 micro M indomethacin (a cyclooxygenase inhibitor), or 10 micro M 17-octadecynoic acid (a cytochrome P(450) inhibitor). In contrast, relaxation was significantly inhibited by either 10 mM tetraethylammonium (nonselective potassium channel inhibitor; P < 0.01) or 50 nM apamin (small conductance potassium channel inhibitor), together with 50 nM charybdotoxin (large and intermediate potassium channel inhibitor; P < 0.01). In the presence of these potassium channel inhibitors, the amount of relaxation was not significantly different (P > 0.50) from that observed in vessels with nonfunctional endothelium. CONCLUSIONS: In isolated porcine ciliary arteries, adrenomedullin induces relaxation that involves CGRP(1) receptors and is in part endothelium dependent. Endothelium-dependent relaxation was blocked by some potassium channel inhibitors, suggesting the possible release of an endothelium-derived hyperpolarizing factor (EDHF).

Reduction of nitrite production by endothelin-1 in isolated porcine ciliary processes.

It has been postulated that endothelin-1 and nitric oxide (NO) could participate in the modulation of aqueous humor dynamic in the eye. This study investigates whether endothelin-1 can reduce the production of nitrite (a stable metabolite of NO) in isolated porcine ciliary processes. Nitrite production was measured (Griess reaction) in the medium surrounding isolated ciliary processes before and after exposure to different drugs. Results are expressed in percent of basal nitrite production. In a concentration-dependent manner (0.1 nM to 1 microM), endothelin-1 significantly decreased basal nitrite production (1 microM: 81.7+/-3.5%; P<0.001). This effect was prevented by the endothelin type A (ETA)-receptor antagonist BQ123 (1 microM: 95.6+/-4.3%; P<0.05), but not by the endothelin type B (ETB)-receptor antagonist BQ788 (1 microM: 83.3+/-4.4%; P=0.86) or by the prostaglandin F2alpha analog unoprostone (30 microM: 86.7+/-3.7%; P=0.74). The adenylcyclase activator forskolin significantly increased basal nitrite production (1 microM: 143.4+/-3.9%, P<0.001). This effect was prevented both by endothelin-1 (0.1 microM; 113.9+/-6.7%: P<0.01) or the nitric oxide synthase inhibitor L-NAME (0.5 mM: 103.3+/-8.4%: P<0.001). The inhibitory effect of endothelin-1 on forskolin-induced nitrite production was significantly reversed by BQ123 (1 microM: 132.4+/-5.1%; P<0.01), but not by BQ788 (1 microM: 112.7+/-4.1%; P=0.64) or unoprostone (30 microM: 109.3+/-4.8%; P=0.98). These results suggest that endothelin-1, through an ETA receptor activation, can reduce both basal and forskolin-induced nitrite production in isolated porcine ciliary processes.

Absence of vasoactive properties of travoprost in isolated porcine ciliary arteries.

BACKGROUND: Ocular blood flow dysregulation is considered to be a risk factor associated with the optic neuropathy observed in glaucoma patients. The present study evaluates the vasoactive effect of the ocular hypotensive agent travoprost (Travatan) on isolated pig ciliary arteries. MATERIAL AND METHODS: Isometric forces were measured with a myograph system. Quiescent vessels were exposed in a cumulative manner to increasing concentrations (0.1 nM - 0.1 mM) of travoprost ([+]-fluprostenol). Vessels pre-contracted with 100 mM potassium chloride (KCl) or 10 nM endothelin-1 were also exposed in a similar manner to travoprost. Time-control experiments without travoprost were always run in parallel. In quiescent vessels, contractions were expressed in percent of 100 mM KCl-induced contractions. In vessels pre-contracted with endothelin-1, relaxations were expressed in percent of the maximal contraction induced by this peptide, while in those pre-contracted with KCl, relaxations were expressed in percent of the plateau-contraction reached 30 minutes after the application of this drug. RESULTS: In quiescent vessels, travoprost had no statistically significant vasoconstrictive effect. In KCl- or in endothelin-1 pre-contracted vessels, travoprost had no statistically significant vasorelaxing effect. CONCLUSIONS: Although the clinical relevance of the results of this study for patients treated with travoprost (Travatan) needs to be further investigated, travoprost appears to have no vasoconstrictive properties in isolated porcine ciliary arteries.

Vasoactive properties of bimatoprost in isolated porcine ciliary arteries.

BACKGROUND: To investigate the vasoactive effect of bimatoprost (Lumigan), a new topical ocular hypotensive agent, in isolated porcine ciliary arteries. MATERIAL AND METHODS: Arteries were placed in a myograph system to measure isometric forces. Quiescent vessels as well as vessels pre-contracted with either 10 nM endothelin-1 or 100 mM potassium chloride (KCl) were exposed, in a cumulative manner, to increasing concentrations (0.1 nM - 0.1 mM) of bimatoprost (dissolved in ethanol). In quiescent vessels, results were expressed in percent of 100 mM KCl-induced contraction. In endothelin-1-pre-contracted vessels, results were expressed in percent of the maximal contraction induced by endothelin-1. In KCl-pre-contracted vessels, results were expressed in percent of the plateau contraction reached 30 minutes after 100 mM KCl application. RESULTS: Bimatoprost induced a significant (p < 0.05 - 0.001) vasoconstriction at concentrations equal to or higher than 0.1 micro M in quiescent vessels (0.1 mM: 73 +/- 12 %). In KCl-pre-contracted vessels, at concentrations higher than 1 micro M, bimatoprost induced significant (p < 0.05 - 0.01) contractions (0.1 mM: 67 +/- 17 %). In endothelin-1-pre-contracted vessels, bimatoprost also induced significant (p < 0.05 - 0.001) contractions at concentrations above 10 micro M (0.1 mM: 17 +/- 8 %). CONCLUSIONS: The present study indicates that bimatoprost appears to have, in vitro, some vasoactive properties in porcine ciliary arteries. The question whether Lumigan has an influence on ocular blood flow needs to be further investigated.

Effect of melatonin on vascular responses of porcine ciliary arteries.

PURPOSE: To investigate the effect of melatonin on isolated porcine ciliary arteries. METHODS: Isolated porcine ciliary arteries were suspended in myograph chambers filled with modified Krebs-Ringer solution (37 degrees C; 95% O2/5% CO2) for isometric tension recording. RESULTS: In quiescent porcine ciliary arteries with endothelium, melatonin (10(-11)--10(-5) M) evoked no change in vascular tone. The highest concentration of melatonin (10(-4 ) M) evoked a small but significant contraction. In vessels precontracted with U-46619 (10(-7) M), increasing concentrations of melatonin (10(-11)--10(-5) M) did not evoke a response. In precontracted arteries with endothelium, contractile response of vascular smooth muscle to increasing concentrations of serotonin (10(-10)--10(-5) M) and noradrenaline (10(-10)--10(-5) M) was reduced after preincubation with melatonin (10(-4) M). Melatonin (10(-4) M) did not alter the response to endothelin-1 (10(-10)--10( -7) M) and U-46619 (10(-10)--10(-6 ) M) in precontracted arteries with endothelium. CONCLUSION: These findings demonstrate that melatonin attenuates the effect of serotonin and noradrenaline and is itself a mild vasoconstrictor in porcine ciliary arteries. The role of melatonin in human ocular circulation remains to be established.

Inhibition by brimonidine of forskolin-induced nitrite production in isolated pig ciliary processes.

PURPOSE: To investigate by which mechanism the ocular hypotensive drug brimonidine (selective alpha(2)-adrenoreceptor agonist) inhibits the production of nitrite induced by forskolin in isolated porcine ciliary processes. METHODS: Nitrite (a nitric oxide metabolite) was measured by Griess reaction in the medium surrounding the ciliary processes, before and after exposure to different drugs. Tissues were exposed for 120 minutes to forskolin (0.1 microM; an adenylylcyclase activator) or 8-bromo-cAMP (10 microM; a cAMP analogue). Some experiments were conducted in the presence of brimonidine (0.01-10 microM), yohimbine (0.1-10 microM; alpha(2)-adrenoreceptor antagonist), prazosin (10 microM; alpha(1)-adrenoreceptor antagonist), nicergoline (10 microM; an alpha(1)-adrenoreceptor antagonist), propranolol (10 microM; a beta-adrenoreceptor antagonist or beta-blocker), and/or pertussis toxin (2 microg/mL; PTX, a G(i)-protein inhibitor). RESULTS: Nitrite production induced by forskolin (133% +/- 6%), but not that induced by 8-bromo-cAMP (133% +/- 6%), was inhibited in a concentration-dependent manner by brimonidine (10 microM: 103% +/- 4%, P < 0.001; EC(50): 0.05 microM). The inhibitory effect of brimonidine was prevented by PTX (119% +/- 7%, P < 0.01) and, in a concentration-dependent manner, by yohimbine (10 microM: 134% +/- 9%; P < 0.01), but not by prazosin, nicergoline, or propranolol. CONCLUSIONS: Reduction of the formation of aqueous humor in the ciliary body's epithelium (and thus an intraocular pressure decrease) after alpha(2)-adrenergic receptor stimulation by brimonidine is known to be associated with a G(i)-protein-mediated inhibition of adenylylcyclase activity. The present study indicates that, through a similar alpha(2)-adrenoreceptor/G(i)-protein pathway, brimonidine can also inhibit nitrite production after adenylylcyclase activation (forskolin-induced) in isolated porcine ciliary processes.

The beta-blocker carteolol inhibits contractions induced by KCl in pig ciliary arteries: an effect modulated by extracellular Ca++.

BACKGROUND: To assess if the vasorelaxing properties of the ocular hypotensive beta-blocker carteolol could share some pharmacological features of calcium-channel antagonists in isolated porcine ciliary arteries. METHODS: In a myograph system (isometric force measurement), quiescent vessels were contracted with increasing concentrations of potassium chloride (KCl: 4.7 - 30 mM) in the presence of different concentrations of extracellular calcium (Ca (++): 0 - 10 mM) and/or carteolol (0 - 1 mM). Vessels precontracted with 20 mM KCl were exposed (cumulative manner) to carteolol (0.03 - 3 mM) in the presence of different concentrations of Ca (++) (0.25, 2.5, 10 mM). Contractions and relaxations are expressed in percent of 100 mM and 20 mM KCl-induced contractions, respectively (mean +/- SEM). RESULTS: Contractions induced by 30 mM KCl (99.0 +/- 4.8 %) were abolished in the absence of Ca (++) and markedly inhibited in the presence of carteolol (1 mM: 40.6 +/- 4.0 %). The inhibitory effect of carteolol on KCl-induced contractions was potentiated (0.25 mM: 6 +/- 2 %) by decreasing and reversed (10 mM: 94 +/- 5 %) by increasing Ca (++) concentrations. Vessels precontracted with KCl were relaxed by carteolol (maximum: 82 +/- 9 %), an effect potentiated (102 +/- 10 %) by lowering or inhibited (27 +/- 11 %) by increasing Ca (++) concentrations. DISCUSSION: The present in vitro pharmacological study, for which in principle no clinical interpretation should be made, suggests that carteolol shares, at rather high concentrations, some characteristics that apparently could mimic certain effects of calcium-channel blockers.

Effect of Xalatan(R) and Cosopt(R) on the vascular tone of quiescent isolated pig ciliary arteries.

BACKGROUND: To investigate whether dilutions of the commercially available Xalatan(R) or Cosopt(R) induce vasoconstrictions in isolated quiescent porcine ciliary arteries. MATERIAL AND METHODS: Contractions measured with a myograph system (isometric force measurement) were expressed in percent of 100 mM potassium chloride(KCl)-induced contraction (mean +/- standard error). In preliminary experiments, vessels were contracted with 100 mM KCl after previous exposures to different dilutions of Xalatan(R) (1/250 to 1/50) or Cosopt(R) (1/500 to 1/5). In a further series of experiments, vessels were exposed in a cumulative manner to different dilutions of Xalatan(R) or Cosopt(R) (1/50 000 to 1/166). RESULTS: Contractions induced by 100 mM KCl were not significantly affected by previous exposure to Xalatan(R) or Cosopt(R) at dilutions higher than 1/166 and 1/50, respectively. However, at the lower dilutions tested, 100 mM KCl-induced contractions were significantly (p < 0.001) and markedly inhibited (1/50 Xalatan(R): 22.1 +/- 2.8 %; 1/5 Cosopt(R): 24.8 +/- 4.6 %). In quiescent vessels, diluted (1/50 000 to 1/166) preparations of Xalatan(R) induced, in a dilution-dependent manner, statistically significant (p < 0.05) but, however very small (3.2 +/- 1.0 %) contractions in comparison to Cosopt(R) (- 0.6 +/- 0.2 %). CONCLUSIONS: Although on the basis of these in vitro experiments no clinical interpretation should be made, at very high dilutions that did not affect KCl-induced contractions, Xalatan(R), but not Cosopt(R), had a very small vasoconstrictive effect in isolated quiescent porcine ciliary arteries. At low dilutions, responses to KCl were inhibited, possibly in relation to an unclear effect of the excipients of Xalatan(R) and Cosopt(R).

Forskolin upregulation of NOS I protein expression in porcine ciliary processes: a new aspect of aqueous humor regulation.

BACKGROUND: To determine whether nitric oxide synthase (NOS) protein expression can be modulated by forskolin in porcine ciliary processes. METHOD: Western blot analysis using mouse monoclonal antibodies against NOS I (neuronal NOS or nNOS), NOS II (macrophage NOS or macNOS), and NOS III (endothelial NOS or eNOS) was performed in porcine ciliary processes. Expression of NOS I and II was also assessed in the presence or in the absence of 1 microM forskolin exposure (4 and 24 hours). RESULTS: All three NOS isoforms could be detected in isolated porcine ciliary processes. Protein expression for NOS I was about 6 times higher than for NOS III and 15 times higher than for NOS II. In comparison to controls, after forskolin exposure, NOS I protein expression was increased by about 1.5-fold. No change could be observed in NOS II protein expression after forskolin exposure. CONCLUSIONS: Nitric oxide is involved in transepithelial fluid transport of different organs (lung, kidney, colon, etc.) and is suspected to play a role in ciliary processes by modulating the aqueous humor production. The present study indicates that forskolin (which increases cAMP production) modulates NOS I protein expression in isolated porcine ciliary processes. These results suggest that selective inhibition of NOS I could be tried for reducing aqueous humor production. The clinical relevance requires further investigations.

Effect of palmitoleic acid on bradykinin-induced endothelium-dependent relaxation in isolated pig ciliary artery.

BACKGROUND: Endothelial-dependent relaxation has been reported to be impaired in some normal tension glaucoma patients. The present study investigates whether the gap junction uncoupling agent palmitoleic acid (PA) affects bradykinin-induced endothelium-dependent relaxation in isolated pig ciliary artery. MATERIAL AND METHODS: In a myograph system (isometric force measurement), vessels precontracted with the thromboxane A2 agonist U 46619 ( approximately 0.1 micrometer) were relaxed by increasing concentrations (cumulative) of bradykinin (0.003 - 3 micrometer). Experiments were repeated in the presence of 100 micrometer L-NAME (inhibitor of nitric oxide formation) and/or 100 micrometer PA. Some experiments were conducted in vessels with a non-functional endothelium (intentionally and mechanically damaged). All experiments were conducted in the presence of 10 microM indomethacin (cyclooxygenase inhibitor). RESULTS: In a concentration-dependent manner, bradykinin evoked a relaxation (101 +/- 2 %) that was abolished in vessels with a non-functional endothelium (maximal relaxation: 7 +/- 1 %, p < 0.001). In the presence of L-NAME, relaxations induced by bradykinin were almost completely inhibited (maximal relaxation: 25 +/- 5 %, p < 0.001). Relaxations evoked by bradykinin were not significantly affected by PA (either in the presence or in the absence of L-NAME). CONCLUSIONS: The bradykinin-induced relaxation, known to be associated in porcine ciliary arteries with an electrical coupling between endothelial and smooth muscle cells, appears to be unaffected by the gap junction uncoupling agent palmitoleic acid. Further investigations are needed to understand the physiology of the endothelium-dependent ocular blood flow modulation that is considered to be dysregulated in some glaucoma patients.