The effects of prostaglandins and endocannabinoids on iris arterial vascularization in Wistar rats - Experimental analysis.

Introduction: The iris vascular supply originates in the anterior and long posterior ciliary arteries. The endothelium influences local blood flow by releasing endothelium relaxing and contracting substances. From a functional perspective, the ocular vascular tonus adjustment is humoral and neural dependent. Objectives: The present article aims to evaluate the possible implications of topical administration of selective COX2 and nonselective COX inhibitors generically named nonsteroidal anti-inflammatory drugs (NSAIDs) and their possible interactions with the endocannabinoid system and the way they could interfere with the vascular tone at the level of ocular iris territory in Wistar rats. Materials and methods: Experimental protocol on Wistar rats was performed in accordance with present laws regarding animal welfare and ethics in animal experiments (Directive 86/ 609EEC/ 1986; Romanian Law 205/ 2004; Romanian Laws 206/ 2004, 471/ 2002 and 9/ 2008; Romanian Order 143/ 400). The studied substances were instilled topically under general anesthesia, and images of the rat iris vessels were captured over a period of 10 minutes. The obtained images were further analyzed using an appropriate hardware and software program. Results: The nonselective NSAIDs induced vascular dilation in the iris vessels, while the selective COX2 inhibitors determined a variable degree of vasoconstriction. Conclusion: In view of the results of this experiment and the added evidence found in literature, we consider that further research will show the potential benefits for the additional use of NSAIDs in ocular pathology, otherwise unaffected by this medication until the present time (for example, glaucoma treatment).

Acute Effect of Hypervolemic Hemodilution on Retrobulbar Hemodynamics in Anterior Ischemic Optic Neuropathy.

PURPOSE: Ischemic ocular disorders may be treated by hypervolemic hemodilution. The presumed therapeutic benefit is based on a volume effect and improved rheological factors. The aim was to investigate the acute effect of intravenous hydroxyethyl starch on retrobulbar hemodynamics in patients with nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: 24 patients with acute NAION were included. Retrobulbar hemodynamics were measured using color Doppler imaging before and 15 min after intravenous infusion of 250 cc 10% hydroxyethyl starch (HES). Peak systolic velocity (PSV), end diastolic velocity (EDV), and Pourcelot's resistive index (RI) were measured in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (PCAs). RESULTS: After infusion of HES blood flow velocities significantly increased in the CRA (PSV from 7.53 ± 2.33 to 8.32 ± 2.51 (p < 0.001); EDV from 2.16 ± 0.56 to 2.34 ± 0.55 (p < 0.05)) and in the PCAs (PSV from 7.18 ± 1.62 to 7.56 ± 1.55 (p < 0.01); EDV from 2.48 ± 0.55 to 2.66 ± 0.6 cm/sec (p < 0.01)). The RI of all retrobulbar vessels remained unaffected. Blood pressure and heart rate remained unchanged. CONCLUSIONS: Hypervolemic hemodilution has an acute effect on blood flow velocities in the CRA and PCAs in NAION patients. Increased blood flow in the arteries supplying the optic nerve head may lead to a better perfusion in NAION patients. This trial is registered with DRKS00012603.

Pharmacology of Serotonin Receptors Causing Contraction of Isolated Bovine Posterior Ciliary Arteries: Role in Ocular Blood Flow.

PURPOSE: To determine the serotonergic (5HT) receptor subtype mediating the contraction of bovine posterior ciliary arteries (BPCAs) in vitro. METHODS: Longitudinal isometric tension was measured in BPCA strips (4-5 mm) mounted in 25 mL organ baths containing oxygenated Krebs solution at 37°C. Cumulative contractile concentration-response (C-R) curves were generated for various 5-HT agonists to assess their potencies and maximal degrees of contraction. Multiple agonist C-R curves were also constructed in the presence and absence of receptor-selective antagonists to determine antagonist potencies using Schild plots. RESULTS: Selective and nonselective agonists for 5-HT receptors elicited concentration-dependent contractile responses in BPCAs with the following rank order of potency: MK-212 > BW723C86 > α-methyl-5-HT >5-methoxy-α-5-methyl-5-HT >> R-DO1 > >5-HT >> cabergoline >> 5-methoxy-dimethyl-tryptamine >> 2-methyl-5-HT >> tryptamine. Interestingly, both 8-OH-DPAT (5HT1A agonist) and quipazine (5HT3 agonist) did not elicit contractions in BPCAs. The contractions produced by BW723C86 (5-HT2B agonist) were antagonized by 5-HT receptor blockers, RS-127445 (5-HT2B antagonist), and M-100907 (5-HT2A antagonist), yielding antagonist pA2 values of 7.5 ± 0.12 (n = 4) and 6.2 ± 0.17 (n = 4), respectively. Furthermore, contractions elicited by MK-212 (5-HT2C agonist) was blocked by RS-102221 (5-HT2C antagonist), although noncompetitively. CONCLUSIONS: On the basis of the pharmacological profile of selective agonists and antagonists, we conclude that serotonin-induced contractions of the BPCA are mediated primarily by a combination of 5HT2C and/or 5HT2B receptors. It appears that 5-HT1A and 5-HT3 receptors are not involved in the contractile action of BPCAs to serotonin.

Vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary arteries in vitro and increased optic disc blood flow in vivo.

PURPOSE: This study aimed to clarify the vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary arteries (PCAs) and to investigate changes in optic disc blood flow after an infusion of L-arginine in vivo. METHODS: Vascular ring segments were mounted on a double myograph system. After obtaining maximal contraction following administration of high-K solution, L-arginine was administrated. Six volunteers received an intravenous drip infusion of 100 ml of L-arginine or saline. Changes in optic disc blood flow were measured by laser speckle flowgraphy. RESULTS: L-arginine relaxed high-K solution-induced contracted rabbit PCAs. Carboxy-PTIO (nitric oxide scavenger) and L-NAME (nitric oxide synthase inhibitor) inhibited L-arginine-induced relaxation in rabbit PCAs. After removal of the endothelium of the rabbit PCAs, L-arginine still relaxed rabbit PCAs. L-arginine relaxed human PCAs, despite the lack of nitric oxide production. In the L-arginine infusion group, the mean blur rate was significantly greater than that of the control group in vivo. CONCLUSION: L-arginine has both nitric oxide-dependent and independent vasodilatory effect on high K- induced contractions in isolated rabbit and human PCAs. L-arginine increased optic disc blood flow in vivo.

Effects of ripasudil hydrochloride hydrate (K-115), a Rho-kinase inhibitor, on ocular blood flow and ciliary artery smooth muscle contraction in rabbits.

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.

Retrobulbar ocular blood flow changes measured by colour Doppler imaging after intra-arterial chemotherapy in retinoblastoma.

PURPOSE: To evaluate the effects of intra-arterial chemotherapy on retrobulbar blood flow parameters in patients with retinoblastoma. METHODS: 20 eyes of 10 patients with unilateral retinoblastoma that were treated with intra-arterial chemotherapy were evaluated using colour Doppler imaging. The peak systolic and end-diastolic velocities of the ophthalmic, central retinal and posterior ciliary arteries were determined. The pulsatility and resistance indices were calculated automatically. The treated eye was compared with the untreated (control) eye and with itself before and after intra-arterial chemotherapy. RESULTS: When comparing the retinoblastoma-containing eyes with the contralateral normal eyes, the peak systolic and end-diastolic velocities of the central retinal artery were significantly higher in the tumorous eyes than in the normal eyes before intra-arterial chemotherapy. Moreover, the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries were significantly decreased after intra-arterial chemotherapy in the tumorous eyes (p<0.05). There were no statistically significant differences in the other parameters. CONCLUSIONS: Our results suggest that intra-arterial chemotherapy has a measurable effect on the retrobulbar blood flow, which can cause a decrease in the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries.

Different effect of serotonin on intracellular calcium ion dynamics in the smooth muscle cells between rat posterior ciliary artery and vorticose vein.

5-hydroxytriptamine (5-HT: serotonin) is an important transmitter that causes vessel constriction, although few studies have examined the effect of 5-HT on venous smooth muscles. The intracellular Ca(2+) concentration ([Ca(2+)]i) plays an essential role in stimulus-response coupling in numerous tissue/cells including vascular smooth muscle cells. The present study was performed to examine whether differences between arteries and veins in the response to 5-HT can be detected under confocal microscope with respect to [Ca(2+)]i dynamics. In posterior ciliary arteries of rats, 5-HT induced a [Ca(2+)]i increase. The 5-HT-induced responses were caused by both Ca(2+) influx and mobilization. Agonist and antagonist experiments revealed that arterial smooth muscles possess 5-HT1a, 1b, 2 (Gprotein-coupled type) and 5-HT3 (ion channel type) receptors, and that 5-HT2 in particular plays a major role in these responses. For vorticose veins, the 5-HT-induced responses were also caused by both Ca(2+) influx and mobilization. However, the cAMP dependent pathway (5-HT4-7) was found to be significant in vasocontraction with respect to 5-HT in these vessels. Thus, Ca(2+) mobilization was induced by 5-HT2 and 5-HT4-7 in a vessel-dependent manner, whereas Ca(2+) influx universally was induced by 5-HT3. These results indicate that the posterior ciliary arteries and vorticose veins in the same tissue might differ greatly in their responses to stimulus.

Inhibitory action of novel hydrogen sulfide donors on bovine isolated posterior ciliary arteries.

In the present study, we investigate the inhibitory effect of novel H2S donors, AP67 and AP72 on isolated bovine posterior ciliary arteries (PCAs) under conditions of tone induced by an adrenoceptor agonist. Furthermore, we examined the possible mechanisms underlying the AP67- and AP72-induced relaxations. Isolated bovine PCA were set up for measurement of isometric tension in organ baths containing oxygenated Krebs solution. The relaxant action of H2S donors was studied on phenylephrine-induced tone in the absence or presence of enzyme inhibitors for the following pathways: cyclooxygenase (COX); H2S; nitric oxide and the ATP-sensitive K(+) (KATP) channel. The H2S donors, NaSH (1 nM - 10 µM), AP67 (1 nM - 10 µM) and AP72 (10 nM - 1 µM) elicited a concentration-dependent relaxation of phenylephrine-induced tone in isolated bovine PCA. While the COX inhibitor, flurbiprofen (3 µM) blocked significantly (p < 0.05) the inhibitory response elicited by AP67, it had no effect on relaxations induced by NaSH and AP72. Both aminooxyacetic acid (30 µM) and propargylglycine (1 mM), enzyme inhibitors of H2S biosynthesis caused significant (p < 0.05) rightward shifts in the concentration-response curve to AP67 and AP72. Furthermore, the KATP channel antagonist, glibenclamide (300 µM) and the NO synthase inhibitor, l-NAME (100 µM) significantly attenuated (p < 0.05) the relaxation effect induced by AP67 and AP72 on PCA. We conclude that H2S donors can relax pre-contracted isolated bovine PCA, an effect dependent on endogenous production of H2S. The inhibitory action of only AP67 on pre-contracted PCA may involve the production of inhibitory endogenous prostanoids. Furthermore, the observed inhibitory action of H2S donors on PCA may depend on the endogenous biosynthesis of NO and by an action of KATP channels.

Effect of tamsulosin on iris vasculature and morphology.

PURPOSE: To determine whether preoperative iris vasculature and morphology are altered in patients who have taken tamsulosin (Flomax). SETTING: Academic multispecialty practice. DESIGN: Case series. METHODS: Patients with current or past tamsulosin use and age- and sex-matched control patients were included. Anterior segment optical coherence tomography (AS-OCT) and iris fluorescein angiography were performed to measure iris vasculature and thickness before cataract surgery. Data collected at surgery included pupil diameter, clinical signs of intraoperative floppy-iris syndrome, and surgical complications. RESULTS: Tamsulosin was currently used by 16 patients and in the past by 4 patients; the control group comprised 10 patients. Pharmacologically dilated pupil diameter was statistically significantly smaller preoperatively and immediately postoperatively in the tamsulosin group than in the control group (P=.009 and P=.003, respectively). There was a statistically significant decrease in pupil size intraoperatively in the tamsulosin group (P=.05) but not in the control group (P=.3). Iris-vasculature parameters, specifically time to first vessel fill and percentage of vessel fill on iris fluorescein angiography, were not significantly different between the 2 groups. The AS-OCT measurements of iris morphology were not statistically significantly different between the groups. No surgical complications occurred. No fluorescein dye leakage, staining, or other vascular anomalies were observed. CONCLUSIONS: Although there were differences in pupil measurements and intraoperative iris behavior between patients who had been on tamsulosin and control patients, there were no significant differences in iris vasculature on iris fluorescein angiography or in iris morphology on AS-OCT.

Unusual adverse choroidal reaction to intravitreal bevacizumab in aggressive posterior retinopathy of prematurity: the Indian Twin Cities ROP screening (ITCROPS) data base report number 7.

PURPOSE: To describe a case of choroidal ischemia in a neonate after single, bilateral, intravitreal bevacizumab (IVB) injection for severe zone 1 aggressive posterior retinopathy of prematurity (AP-ROP). METHODS: A six-week-old baby, born at a gestation age of 28 weeks and birth weight of 1.08 kg, presented at a postconceptional age of 34 weeks for ROP screening. On examination, both eyes revealed engorged iris new vessels with poorly dilating pupils. Retinal examination showed media haze, severe zone 1 APROP with confluent new vessels, severe plus disease, and early vitreous condensation at the edge of new vessels for 12 clock hours. The child was treated bilaterally, with single IVB injection before laser. After 16 hours, hypotony and exudative retinal detachment with patches of choroidal whitening suggestive of choroidal ischemia were seen. RESULTS: The child was treated with topical steroids and cycloplegic drops and exudative retinal detachment resolved on the tenth day. Initial resolution of new vessels showed recurrence after two weeks and was treated with laser photocoagulation. Stable retinopathy status was noted up to six months follow-up. CONCLUSION: Choroidal ischemia secondary to a single IVB injection for the treatment of AP-ROP could be an unusual complication which raises the concern of its use as a monotherapy in neonates.

Pharmacological actions of the slow release hydrogen sulfide donor GYY4137 on phenylephrine-induced tone in isolated bovine ciliary artery.

Hydrogen sulfide (H2S), a colorless gas characterized by its pungent odor of rotten eggs has been reported to elicit relaxation effects on basal and pre-contracted non-ocular smooth muscles of several mammalian species. In the present study, we investigated the pharmacological actions of a H2S donor, GYY4137 on isolated bovine posterior ciliary artery after contraction with the adrenergic receptor agonist, phenylephrine. Furthermore, we studied the underlying mechanism of inhibitory action of GYY4137 on the posterior ciliary arteries. Isolated bovine posterior ciliary arteries were mounted in oxygenated organ baths and changes in isometric tension were measured with a Grass FT03 transducer connected to a recorder using a Grass Polyview Software. The relaxant actions of GYY4137 on phenylephrine pre-contracted arteries were observed in the absence and presence of an inhibitor of cyclo-oxygenase, flurbiprofen. Furthermore, the inhibitory effects of GYY4137 were studied in the absence or presence of inhibitors/activators of biosynthetic enzymes for H2S and nitric oxide production, as well as specific ion channel blockers. In the concentration range, 100 nM to 100 µM, GYY4137 elicited a concentration-dependant relaxation of phenylephrine-induced tone in isolated posterior ciliary arteries, with IC50 value of 13.4 ± 1.9 µM (n = 6). The cyclo-oxygenase inhibitor, flurbiprofen, significantly (p < 0.01) enhanced the relaxation induced by GYY4137 yielding IC50 value of 0.13 ± 0.08 µM (n = 6). Both the inhibitors of cystathionine ß-synthase (aminooxyacetic acid, AOAA, 30 µM) and cystathionine γ-lyase (propargylglycine, PAG, 1 mM) caused significant (p < 0.05) rightward shifts in the concentration-response curve to GYY4137. Furthermore, the KATP channel antagonist, glibenclamide (100 µM) significantly (p < 0.01) attenuated the relaxant action induced by GYY4137 on bovine ciliary artery. Conversely, the activator of cystathionine ß-synthase, SAM (100 µM) and an inhibitor of nitric oxide synthase, L-NAME (100 µM) had no significant effect on relaxations induced by GYY4137. We conclude that the inhibitory action of GYY4137 on isolated bovine ciliary artery is dependent upon the endogenous production of both prostanoids and H2S. Furthermore, the observed vascular smooth muscle relaxation induced by GYY4137 is mediated, at least in part, by KATP channels.

Dual effect of prostaglandins on isolated intraocular porcine ciliary arteries.

PURPOSE: Prostaglandin analogues are used to reduce the intraocular pressure (IOP) in glaucoma, but also affect the tone of the arteries supplying the ciliary body. Previously, the effect of prostaglandins has been studied on the extraocular ciliary arteries, whereas the effect on intraocular ciliary arteries has not been studied in detail. METHODS: Intraocular long posterior porcine ciliary arteries were isolated and mounted in a myograph system for isometric tension recording, and the effects of PGF2α , the prostaglandin analogue latanoprost, PGD2 , PGE2 , PGI2 and the thromboxane analogue U46619 were studied in the presence and absence of selective receptor antagonists. RESULTS: The prostaglandins PGD2 and PGE2 induced relaxation at low concentrations (10(-9) - 3 × 10(-7) m), which could be inhibited by blocking either the DP or the EP4 receptor, whereas PGD2 , PGE2 , PGF2α , latanoprost and U46619 induced contraction at high concentrations (10(-6) - 10(-5) m), which could be inhibited by blocking the TP receptor. Additionally, blocking of the FP receptor induced a right-shift of latanoprost-induced contraction. CONCLUSIONS: Prostaglandins with affinity to DP1 and EP4 receptors induce relaxation at low concentrations, and prostaglandins with affinity to TP and FP receptors induce contraction at high concentrations of intraocular porcine ciliary vessels in vitro. The findings may contribute to understanding the regulation of blood flow to the ciliary body.

Vasodilatory effects of antivascular endothelium growth factor (VEGF) antibody, corticosteroid, and nitric oxide on the posterior ciliary arteries.

PURPOSE: The purpose of this study was to determine whether an antivascular endothelium growth factor (VEGF) antibody, a corticosteroid, and sodium nitroprusside (SNP) [a nitric oxide (NO) donor] are possible treatment agents for nonarteritic ischemic optic neuropathy (NAION) by clarifying their effects on high-K (potassium) solution-induced contraction in isolated rabbit and human posterior ciliary arteries (PCA). METHODS: Vascular ring segments were cut from the distal section of the PCA and mounted in a double-myograph system. After obtaining the maximal contraction following the administration of high-K solution, bevacizumab as an anti-VEGF antibody, methylprednisolone as a corticosteroid, and SNP were administered separately. When a vasodilatory effect was observed, carboxy-PTIO (a NO scavenger) or L-NAME (a NO synthase inhibitor) was administered. RESULTS: Bevacizumab did not relax either the rabbit or the human PCA, whereas methylprednisolone relaxed both. Neither carboxy-PTIO nor L-NAME inhibited methylprednisolone-induced relaxation. SNP relaxed the rabbit PCA. Carboxy-PTIO inhibited SNP-induced relaxation, but L-NAME did not. In the human PCA, the vasodilatory effect of SNP was present, but weaker than in the rabbit PCA. CONCLUSIONS: A corticosteroid has NO-independent vasodilatory effects. Exogenous NO has a weak dilating effect in the human PCA. Therefore, corticosteroid could be effective for the treatment of NAION.

The effects of prostaglandin analogues on intracellular Ca2+ in ciliary arteries of wild-type and prostanoid receptor-deficient mice.

PURPOSE: To clarify the mechanism of prostaglandin (PG) analogue-dependent relaxation in ciliary arteries from wild-type (WT) and prostanoid receptor-deficient mice. METHODS: The intracellular-free calcium concentration ([Ca(2+)](i)) in isolated WT mouse ciliary arteries was measured by fluorescence photometry. Reduction of [Ca(2+)](i) leading to vascular relaxation by PG analogues latanoprost, isopropyl unoprostone, or tafluprost was compared to the maximum increase of [Ca(2+)](i) by 50 mM KCl. The cyclooxygenase inhibitor indomethacin and the NO synthase inhibitor N(G)-nitro-(L)-arginine methylester ((L)-NAME) were added to investigate the involvement of vascular endothelial factors. Moreover, PG analogue-dependent reduction of [Ca(2+)](i) was measured in ciliary artery strips from FP, EP1, EP2, and EP3 receptor-deficient mice. RESULTS: The 3 PG analogues reduced K(+)-dependent increase in [Ca(2+)](i) in a concentration-dependent manner. Indomethacin (10 µM) had little effect. The reductions of [Ca(2+)](i) induced by 10 µM PG analogues were not significantly affected by the treatment with the NO synthase inhibitor (L)-NAME (10(-4) M). The effect of all 3 PG analogues in FP and EP3 receptor-deficient arteries was similar to the effect in WT arteries. Latanoprost significantly enhanced the reduction of [Ca(2+)](i) in ciliary arteries from prostanoid EP1 and EP2 receptor-deficient mice compared to WT mice. Tafluprost had a similar effect in arteries from EP2 receptor-deficient mice. CONCLUSIONS: PG analogues latanoprost, isopropyl unoprostone, and tafluprost reduced the K(+)-dependent increase in [Ca(2+)](i) in isolated mouse ciliary arteries. Endothelial-derived factors and FP and EP3 receptors were not involved in the responses. The increased effectiveness of latanoprost and tafluprost in reducing [Ca(2+)](i) in EP1 and EP2 receptor-deficient arteries suggests that the PG analogues may act, at least partially, through nonprostanoid receptor pathways. For glaucoma patients, PG analogues can be selected to reduce the intraocular pressure and increase the ocular blood flow.

Dual effects of ATP on isolated arteries of the bovine eye.

Although the presence of purinoreceptors has been shown in many human and animal arteries, there is few data yet about their role in the arteries of the eye. The purpose of the present study was to evaluate the effects of several agonists of purinoreceptors on isolated arteries of the bovine eye. Responses of isolated preparations of bovine ophthalmic (OA) and posterior ciliary arteries (PCA) to agonists of purinoreceptors (ATP, α,ß-methylene-ATP-α,ß-meATP, 2-methylthioATP-2meSATP, uridine-5'-triphosphate-UTP) as well as agonists of adreno-, cholino-, adenosine and histamine receptors were recorded by a standard organ bath method. ATP induced contractions of the intact vessels but caused relaxation of α,ß-meATP-pretreated arteries. Contractile responses of PCA to high concentrations of ATP and α,ß-meATP were significantly stronger than responses of OA, as well as relaxative responses to ATP and adenosine were significantly stronger in PCA than in OA. We suggest that there are several subtypes of functionally active purinoreceptors in both OA and PCA, although the potency of agonists of purinoreceptors to produce mechanical responses is higher in PCA than in OA. Purinoreceptors can be potential targets for new drugs, treating vascular pathology of the eye.

Does phacoemulsification under topical anesthesia affect retrobulbar blood flow?

PURPOSE: To investigate with color Doppler imaging the effects of phacoemulsification surgery under topical anesthesia on retrobulbar vessels hemodynamics. METHODS: In this prospective study, color Doppler imaging was used to measure the maximum (Vmax) and minimum flow velocity (Vmin) of the central retinal vein, and the Vmax and Vmin, pulsatility index and resistance index of the central retinal artery, nasal, and temporal posterior ciliary arteries, and ophthalmic artery blood flow before and 1 day after phacoemulsification surgery under topical anesthesia. RESULTS: After phacoemulsification surgery under topical anesthesia, Vmin of the central retinal artery increased (p ≤ 0.05), whereas the other variables showed no significant change. CONCLUSIONS: Phacoemulsification surgery under topical anesthesia has a minor effect on retrobulbar blood flow. Therefore topical anesthesia should be suitable for patients with ocular perfusion disorders (eg, glaucoma).

Changes in corneal innervation and sensitivity and acetylcholine-mediated vascular relaxation of the posterior ciliary artery in a type 2 diabetic rat.

PURPOSE: Corneal confocal microscopy is emerging as a clinical tool to evaluate the development and progression of diabetic neuropathy. The purpose of these studies was to characterize the changes in corneal sensitivity and innervation in a rat model of type 2 diabetes in relation to standard peripheral neuropathy endpoints. Assessment of diabetes-induced changes in corneal innervation and sensitivity in animal models will be important for determining the usefulness of corneal markers for preclinical studies to test potential new treatments for diabetic neuropathy. METHODS: High-fat/low-dose streptozotocin diabetic rats were used to examine diabetes-induced changes in standard diabetic neuropathy endpoints and innervation of the cornea using confocal microscopy, corneal sensitivity using a Cochet-Bonnet esthesiometer, and vascular reactivity of the posterior ciliary artery. RESULTS: Compared with age-matched control rats, the induction of hyperglycemia in rats fed high-fat diets caused a decrease in nerve conduction velocity, thermal hypoalgesia, and intraepidermal nerve fiber profiles. In the cornea there was a decrease in corneal nerve fiber length and sensitivity. In addition, vascular relaxation in response to acetylcholine was decreased in the posterior ciliary artery. CONCLUSIONS: These studies suggest that in a type 2 diabetic rat model, changes in corneal nerve innervation and sensitivity occur that are consistent with changes seen in diabetic patients. Corneal sensitivity and innervation may be valuable endpoints for examining the potential treatments of diabetic neuropathy in preclinical studies.

Effects of Rho-associated protein kinase inhibitors Y-27632 and Y-39983 on isolated rabbit ciliary arteries.

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(2+)](i)) 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 (G)-nitro-L: -arginine methyl ester (L: -NAME) or 10 µM indomethacin. In Ca(2+)-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(2+)](i) 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(2+) concentration.

Effects of anti-glaucoma drugs on resistive index of the medial long posterior ciliary artery using color Doppler imaging in Beagle dogs.

Color Doppler imaging (CDI) was carried out to evaluate the effects of anti-glaucoma drugs on ophthalmic circulation using CDI-derived resistive index (RI) values. CDI was performed on nine Beagle dogs, and RI values were calculated for the medial long posterior ciliary artery before and after the administration of anti-glaucoma drugs. A significant increase in RI values was found after topical administration of levobunolol (p < 0.05) or dipivefrin (p < 0.05). Pilocarpine showed no effects on RI values after topical administration. The results suggest that some anti-glaucoma drugs could affect ophthalmic blood flow.