CGRP in relation to neurogenic inflammation and cAMP in the rabbit eye

The effects of topical application of neutral formaldehyde (1%) and intracameral administration of calcitonin gene-related peptide (CGRP, 0.5- or 2.0 micrograms) on the intraocular pressure (IOP), blood-aqueous barrier, pupil size, blood pressure and cyclic AMP (cAMP) content in the aqueous humour of a rabbit were studied. Topical chemical irritation with 1% formaldehyde caused a typical irritative response in the eye with a rise in the IOP, breakdown of the blood-aqueous barrier and miosis. The cAMP content in the aqueous humour was also increased (88.5 +/- 35.0 pmol ml-1, P less than 0.05) when compared with the control group (16.3 +/- 3.6 pmol ml-1). Intracameral administration of CGRP caused a rise in the IOP, breakdown of the blood-aqueous barrier and also systemic hypotension. Miosis was not observed after intracameral CGRP but an increase in the cAMP content in the aqueous humour was seen (130.5 +/- 30.3- and 158.7 +/- 48.1 pmol ml-1, both P less than 0.01, after 0.5 or 2.0 micrograms, respectively). The cAMP concentration in the aqueous humour after topical chemical irritation and intracameral CGRP correlated with the intensity of the breakdown of the blood-aqueous barrier. CGRP seems to cause most, but not all, of the ocular changes after sensory nerve stimulation elicited by topical neutral formaldehyde. Of these CGRP-induced changes, only the breakdown of the blood-aqueous barrier is related to an increase in the cAMP content in the aqueous humour. Contralateral responses after sensory nerve stimulation were similar to contralateral responses to intracameral CGRP.     

Determination of the pseudofacility by fluorophotometry in the human eye

Purpose: Pseudofacility (decrease in aqueous humor flow in response to increase in the intraocular pressure (IOP)) has been evaluated in animals and in humans by a combination of different techniques that seriously alter the ocular physiology, such as the cannulation of the eyeballs, use of radioactive isotopes, perilimbic suction cups or tonography. Very different results have been obtained. Our objective is to relate the value of the aqueous humor flow in humans (as measured by fluorometry) with IOP. In order to obtain the widest range of IOP possible, we have performed this study in both normal as well as glaucoma patients. Methods: 48 eyes were studied, corresponding to 31 subjects (mean age 58 ± 14 years). Of these, 21 corresponded to normal subjects and 27 to glaucoma patients. The aqueous humor flow (F) was determined by fluorophotometry (Protocol of Yablonsky) and the IOP was measured thereafter. Results: The mean value of F was 2.1 ± 0.5 l/min for healthy eyes and 2.2 ± 0.7 l/min for glaucoma-affected eyes. The values were not different (p > 0.1). The mean value of the IOP was 15.3 ±3.1 mmHg in the normal population and 22.1 ± 4.3 mmHg in the glaucoma patients. A linear relationship between F and IOP was found (r = – 0.41, p < 0.05, decrease in F = 0.081 l min^–1 mmHg^–1). Conclusions: The value of the pseudofacility in the humans can be estimated at 0.081 l min^–1 mmHg^–1, which constitutes 27% of the total outflow facility. This figure also makes it possible to estimate the role of the ultrafiltration in blood in the production of the aqueous humor since it is assumed that active secretion is pressure-independent. The results obtained are concordant with a secondary but no unimportant role of the plasmatic ultrafiltration with respect to the active secretion.     

Sensory mediation of the ocular response to neutral formaldehyde

Topical application of 100 or 250 μg neutral formaldehyde to the rabbit eye elicits an acute inflammatory response consisting of a raised intraocular pressure (IOP), anterior uveal vasodilation, miosis and an increase in protein in the aqueous humour. Prior treatment with 0·4% benoxinate (12 drops over 30 min) inhibited these ocular changes whereas systemic indomethacin or atropine pretreatment had no notable effect. No raised levels of prostaglandin-like activity were observed in any samples of aqueous humour withdrawn 15 min after stimulation with formaldehyde. The major site of breakdown of the blood-aqueous barrier was shown by fluorescein angiography and colloidal carbon vascular “labelling” to occur in the ciliary processes.The IOP response to 6–50 μg formaldehyde administered intracamerally during closed circuit perfusion was greatly reduced by benoxinate or intracamerally infused tetrodotoxin. Furthermore the response was essentially abolished in eyes in which the ipsilateral sensory nerve supply had been destroyed by diathermic coagulation of the ophthalmic branch of the trigeminal nerve. The response to submaximal doses of formaldehyde was greater in the unilaterally sympathectomized eye than in the fellow control eye.These observations indicate that the ocular response to this form of chemical irritation is dependent largely, if not entirely, upon a non-prostaglandinergic and non-cholinergic excitatory pathway most likely occurring in sensory nervous elements.     

The effect of the water-drinking test on aqueous humor dynamics in healthy volunteers

In 19 healthy volunteers (9 men, 10 women) we studied the effect of drinking 1000 ml of water within 10 min on aqueous humor dynamics. Fluorescein was applied topically five times, 6 h before measurements. All readings were taken during the afternoon. The Wilcoxon signed-rank test was used to evaluate the statistical relevance of the data. Aqueous humor flow was measured 60 min before (F1) and 10 min (F2), 30 min (F3), 60 min (F4) and 90 min (F5) after drinking 11 of water. Flow (mean ± SD) changed as follows: F1, 2.25 ± 1.2 ll/min ; F2, –3.29 ± 3.4 /min (P < 0.0000); F3, 1.69 ± 1.0 gml/min (P=0.007); F4, 2.39±0.9 l/min (P=0.25); F5, 2.64±0.9 l/min (P=0.02). Three to four days later the identical procedure was performed in each individual: F1, 2.06 ± 1.0 l/min F2, –3.12 ± 2.4 l/min (P < 0.0000); F3, 1.09 ± 0.6 l/min (P < 0.0001); F4, 1.76 ± 0.6 l/min (P=0.15); F5, 2.54±0.8 l/min (P=0.01). The correlation coefficient for the left and night eyes (F1–F5, both days) was r=0.85. The mean flow in the 19 healthy volunteers during the afternoon hours was 2.25 ± 1.0 l/min. Water load consistently led to a reflux of unbound fluorescein into the eye about 10 min later. This is documented as a negative flow. Ninety minutes after drinking 1000 ml of water there is a significant increase in flow, which is in contrast to the normal diurnal curve of aqueous humor dynamics. Water load causes hydremia and an increase in episcleral venous pressure. Fluorophotometry together with water load may be useful to study the aqueous humor dynamics in healthy and glaucomatous eyes and eyes with ocular hypertension.     

The effect of latanoprost 0.005% once daily versus 0.0015% twice daily on intraocular pressure and aqueous humour protein concentration in glaucoma patients. A randomized, double-masked comparison with timolol 0.5%

Background: Latanoprost is a PGF₂ analogue which reduces the intraocular pressure (IOP) by increasing the uveoscleral outflow. The objective of this study was to investigate the effect of two different regimens of latanoprost on the diurnal IOP and also the effect of latanoprost on the blood-aqueous barrier measured with a laser flare cell meter (Kowa FM-500). Moreover, the safety aspects of the two regimens regarding hyperemia were studied. Methods: A double-masked, randomized study was performed in 30 patients (9 males, 21 females; mean age 61.9 years) with primary open-angle glaucoma or pseudoexfoliation glaucoma. Twenty patients were treated with latanoprost 0.0015% twice daily or 0.005% once daily for 3 weeks in a cross-over design. Ten patients received timolol 0.5% twice daily as control. Results: Latanoprost 0.005% once daily reduced IOP (± SEM) more effectively than latanoprost 0.0015% twice daily (9.8±0.9 mm Hg and 6.7±0.9 mm Hg, respectively). There was a statistically significant increase in the aqueous humour protein concentration within the timolol group (P=0.004), but not within the latanoprost group (P=0.97). There was no statistically significant difference in the change in aqueous humour protein concentration from baseline between latanoprost and timolol groups (P=0.08). No statistically significant difference in conjunctival hyperemia between the two latanoprost regimens was found (P=0.37). Conclusion: Latanoprost 0.005% once daily reduced IOP more effectively than latanoprost 0.0015% twice daily (P<0.001). Latanoprost had no statistically or clinically significant effect on the blood-aqueous barrier. There was no difference in hyperemia between the two regimens. Both concentrations of latanoprost reduced IOP at least as well as timolol 0.5% eye drops.     

Intraocularer Druck und Kammerwasserzirkulations-Untersuchungen an Kaninchenaugen nach intravenöser Verabreichung von Propranolol (Inderal®)

Zusammenfassung Der intraoculare Druck der mit Urethan anaesthesierten Kaninchen betrug 20,8 mm Hg. I.v. verabreichtes Propranolol (Inderal, 0,3 mg/kg Körpergewicht) verringerte diesen Druck auf 18,8±1,3 mm Hg. Die totale Leichtigkeit des Kammerwasserabflusses an den Kontrollaugen betrug 0,309±0,090 l/mm Hg/min, während sich nach Verabreichung von Propranolol dieser Wert auf 0,237 ±0,083 l/mm Hg/min veränderte. Die Kammerwasserproduktion in den Kontrollaugen betrug 2,16±0,78 l/min. Nach Verabreichung von Propranolol ging sie auf 1,15±0,64 l/min zurück. Die Differenzen erwiesen sich als statistisch signifikant. Die Abnahme der Abflußleichtigkeit erscheint den Daten nach geringer als die Abnahme der Kammerwasserproduktion. Dadurch erklärt sich die Verringerung des intraocularen Druckes. Aufgrund des Vergleiches der verschiedenen und von einander abweichenden Literaturangaben vermuten die Verfasser, daß das Propranolol außer der tonusverringernden Wirkung auf die -adrenergen Receptoren auch noch einen anderen Wirkungsmechanismus entfalten kann.

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Intraocular pressure and circulation of aqueous humour in rabbit eyes following intravenous administration of propranolol (Inderal^®)

Summary The intraocular pressure of rabbits under urethan anaesthesia was found to be 20.8±2.4 mm Hg. 0.3 mg/kg body weight propranolol given intravenously lowered intraocular pressure to 18.8±1.3 mm Hg. The total facility of outflow from control eyes examined at constant pressures of perfusion was 0.309 ±0.09 l/mm Hg/min, which was reduced to 0.237±0.08 l/mm Hg/min by propranolol given systemically. The formation of aqueous humor in the control eyes was 2.16±0.78 l/min, which was diminished to 1.15±0.64 l/min by propranolol. The differences are statistically significant. The decrease in facility of outflow is smaller than the decrease in formation of aqueous humour, which accounts for the lower intraocular pressure. On the basis of the various and gently differing data in the literature it is assumed that propranolol may have some other mode of action in addition to its -adrenolytic effect on receptors.

     

Ocular irritative response to YAG laser capsulotomy in rabbits: release of calcitonin gene-related peptide and effects of methysergide.

The Neodymium (Nd):YAG laser is commonly used in ophthalmology mainly for the posterior capsulotomy in patients with secondary cataract after extracapsular cataract extraction. A frequent side-effect following different kinds of YAG laser treatments is an acute increase in the intraocular pressure (IOP). The present study addresses the role of calcitonin gene-related peptide (CGRP) in the ocular irritative response following YAG laser anterior capsulotomy in rabbits. The YAG laser anterior capsulotomy caused an irritative response in the eye, which consisted of an increase in the IOP, miosis and breakdown of the blood-aqueous barrier. Following YAG laser capsulotomy, CGRP-immunoreactivity was found in the aqueous humour in different molecular weight forms as revealed by gel-permeation chromatography. One of the peaks coeluted with synthetic human CGRP. Methysergide attenuated the increase in the IOP and disruption of the blood-aqueous barrier, but not the miosis, following YAG laser anterior capsulotomy. The present study demonstrates the release of CGRP into the aqueous humour following YAG laser capsulotomy, and suggests that CGRP is partly causing the increase in IOP and disruption of the blood-aqueous barrier in this irritative response.     

Effect of topical chemical irritation on the blood-aqueous barrier of the rat eye

The effect of topical neutral formaldehyde on the blood-aqueous barrier of the rat was studied. Thirty minutes after irritation, the protein concentration of the aqueous humour had increased from the control value of 1.95 +/- 0.25 to 2.95 +/- 0.45 mg/ml (p less than 0.05). Extravasation of Evans blue dye from the iris vessels after irritation could be demonstrated by fluorescence microscope. These changes could be eliminated by prior denervation of the trigeminal sensory nerve. The present work demonstrates that the eye of the rat responds to topical chemical irritation. This response is dependent on sensory innervation.     

Combined cataract and glaucoma surgery: endoscope-controlled erbium:YAG-laser goniotomy versus trabeculectomy

Background To compare endoscopic infrared laser trabecular ablation and trabeculectomy (both combined with cataract surgery) regarding intraocular pressure (IOP), visual acuity, antiglaucomatous drugs and complications.Methods Seventeen eyes of 14 patients [age 74.7±11.7 years (arithmetic mean ± standard deviation)]—13 with primary open-angle glaucoma (POAG) and four with pseudoexfoliation glaucoma (PEXG)—underwent standard cataract surgery. After lens implantation, a probe (1.1 mm external diameter) with optic and laser fibres and an irrigation tube was introduced through the cataract incision. To perforate Schlemms canal, 15–17 single pulses (16 mJ, 160 s) were applied using a photoablative infrared laser (Er:YAG, =2.94 m). All eyes except one received antiglaucoma treatment. The control group treated with cataract surgery and trabeculectomy consisted of 17 eyes (13 POAG, four PEXG) of 15 patients (age 75.0±5.6 years), each eye received antiglaucoma treatment.Results Mean follow-up was 3 years. The eyes treated with the endoscopic laser showed a mean preoperative IOP of 23.3±4.3 mmHg, which was reduced to 15.0±2.1 mmHg (mean IOP lowering 33.7%) after 3 years. Five eyes needed no medication for IOP-control after the procedure. Two eyes needed further surgery for IOP-control. In the control group, mean IOP was 24.5±2.6 mmHg in the beginning and 17.3±6.2 mmHg after 3 years, corresponding to a 33.3% lowering of IOP. Six eyes needed no medication, four eyes needed further surgery to lower IOP.Conclusions After 3 years follow-up of a small pilot group, combined endoscopic infrared laser surgery with cataract surgery seems to be a safe and effective way to lower IOP. It shows the same ability to lower IOP as combined cataract surgery with trabeculectomy. In addition, there are markedly less complications with the endoscope-controlled photoablative laser procedure.The authors have no proprietary interest in the techniques used. This study was presented in part at the 101st meeting of the Deutsche Ophthalmologische Gesellschaft (DOG), Berlin, 2003.     

Increased release of tenascin in tear fluid after photorefractive keratectomy

Background: Extracellular matrix protein tenascin (TN) is expressed in the anterior stroma during corneal wound healing. In this study we analysed TN release in tear fluid after photorefractive keratectomy (PRK). Methods: Tear fluid TN concentrations of ten PRK patients were measured with an immunoassay. Tear fluids were collected preoperatively and 1, 2 and 7 days after PRK. The tear fluid collection time and the volume of tears collected were registered. Because tear fluid flow was greatly increased postoperatively, tear fluid flow-corrected release (TN flux) was calculated. Results: The tear fluid flow was 4.50±0.94 l/min (mean±SEM) preoperatively, 55.48±16.70 l/min (P<0.01) on the 1st, 33.91±7.91 l/min (P<0.01) on the 2nd, and 13.79±5.49 l/min (P>0.05) on the 7th postoperative day. The preoperative TN concentration was 0.85±0.20 g/ml. On the 1st postoperative day it decreased to 0.37±0.17 g/ml (P>0.05), most likely due to the dilution effect caused by hypersecretion after PRK. The TN concentration was 0.67±0.12 g/ml (P>0.05) on the 2nd and 0.78±0.15 g/ml (P>0.05) on the 7th postoperative day. The preoperative TN flux was 5.23±1.88 ng/min. On the 1st and 2nd postoperative days the TN flux was 14.40±4.99 ng/min (P<0.05) and 22.66±6.I2 ng/min (P<0.05), respectively. On the 7th postoperative day a tendency towards decreased flux (14.00±6.02 ng/min, P>0.05) was observed. Conclusion: Although there is a minor decrease in TN concentration after PRK due to increased tear fluid flow, a significant increase in TN flux was observed. Complete reepithelialization of the ablated area was observed in all eyes at the follow-up visit on postoperative day 7.     

Does aqueous humor secretion decrease with age?

Aqueous humor flow was calculated during day-time in 148 healthy volunteers and 75 older patients using the Fluorotron Master II anterior chamber protocol (Coherent, Palo Alto, USA). Healthy volunteers as well as patients had no history of ocular pathology, surgery or laser treatment. Slitlamp examination revealed no ocular pathology. Hypertension, diabetes, local and systemic drug therapy, neoplasia, kidney or liver disease, contact lens and ocular trauma were excluded. Mean age of volunteers was 26.5±3.8 years; age of patients: 65.5±10.5 years. Aqueous humor flow during day-time in healthy volunteers in the OD: (mean± s.d.) 2.26±1.0l/min, in the OS: 2.17±1.0l/min. Correlation coefficient: r=0.8. The mean aqueous humor flow in the older patients during day-time: OD: 1.91±1.1 l/min, OS: 1.86±1.1 l/min. Correlation coefficient: r=0.54. The Mann-Whitney-U-test revealed a significant difference when comparing the right eyes of healthy volunteers with the right eyes of patients (p<0.01). When comparing all left eyes the difference is also significant (p=0.01). The results of the study underline, that the mean aqueous humor secretion does significantly decrease with age. However, the data show that there is only a slight decrease of flow of approximately 2.5% per decade. From the clinical point of view it should be concluded, that although the aqueous humor secretion does decrease with age, this is not of clinical importance, even in cases of glaucoma surgery. Afterall we still don't know, whether this decrease of aqueous humor flow is caused by a decrease of the pigmented and non-pigmented epithelium cells, or via a decrease of outflow facility, or via a decrease of CNS-stimulation.     

Endothelin-like immunoreactivity in aqueous humor of patients with primary open-angle glaucoma and cataract

Background: Experimental evidence suggests a role of endothelin-1 (ET) in the regulation of intraocular pressure (IOP). Method: Therefore, inpatients undergoing cataract surgery, ET-like immunoreactivity (STIR) was measured by radioimmunoassay in pooled samples of aqueous humor of eyes with primary open-angle glaucoma (POAG) and normotensive eyes with cataract only. Results: ETIR was significantly (P < 0.05) higher in patients with cataract and POAG (20.5 ± 1.8 pg/ml,n = 12; preoperative IOP 21.4 ± I.1 mmHg,n = 33) than in patients with cataract only (15.8 ± 1.6 pg/m1,n = 15; preoperative IOP 16.0 ± 0.6 mmHg,n = 77). Conclusion: This finding may indicate a role of ET in POAG or ocular antihypertensive treatment, and its relevance should be further investigated.     

Immediate increase in aqueous humour endothelin 1 concentration and intra-ocular pressure after argon laser trabeculoplasty in the rabbit

PURPOSE: To investigate the immediate changes of aqueous humour endothelin 1 (ET-1) concentration and intra-ocular pressure (IOP) after argon laser trabeculoplasty (ALT) in the rabbit. METHODS: Standard ALT was performed in one eye of 11 pigmented rabbits. IOP was measured with a Tono-Pen-2 tonometer before treatment, under general anaesthesia. Postlaser IOP measurements followed by aqueous humour aspiration were performed under general anaesthesia 30 and 60 min after treatment in 6 and in 5 animals, respectively. RESULTS: The aqueous humour ET-1 concentration was significantly higher (55.0 pg/ml) after ALT than in the contralateral eyes without laser treatment (8.2 pg/ml, p = 0.001). IOP increased significantly after ALT (p = 0.007) but remained unaltered (p = 0.10) in the contralateral eyes without treatment. No statistically significant difference was found either in postlaser IOP elevation or in interocular ET-1 difference between the groups. CONCLUSIONS: The results suggest that in the rabbit the increase in aqueous humour ET-1 concentration after ALT is immediate, detectable even 30 min after the laser treatment, followed by no further increase during the second 30-min period after ALT, and associated with an immediate postlaser IOP elevation within 1 h after ALT. These findings may suggest a similar response to ALT in the human eye, since a similar immediate IOP elevation is frequently observed after ALT in the clinical practice.     

The time course of laser-induced disruption of the blood aqueous barrier in the rabbit

The response of the blood aqueous barrier to a defined laser trauma was investigated in a series of seven groups with three pigmented rabbits in each group. The peripheral iris of the left eye was treated with the Argon laser (ten spots of 50-m size with an energy of 100 mJ). The right eyes served as controls. The anterior chambers of both eyes were tapped at given time intervals after the laser coagulation to enable the analysis of the protein content of the aqueous humour and for the assay of the lactate dehydrogenase activity. Within 100 min after laser treatment a positive correlation between time and protein concentration in the anterior chambers of the treated eyes (r = 0.77) and in the untreated eyes (r = 0.79) was established. There was a significant response on the blood aqueous barrier in the untreated fellow eyes. The activity of the lactate dehydrogenase showed a significant increase 5, 70 and 100 min after laser trauma in the treated eyes only. The laser trauma induced a significant increase ( = 0.01) in the intraocular pressures of the treated eyes, which persisted up to 70 min after treatment. The clinical implications of these findings are discussed.     

Change in Corneal Permeability to Timolol After Laser In Situ Keratomileusis and Photorefractive Keratectomy in Rabbit

Purpose To evaluate the change in corneal permeability to timolol 1 month after laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK) in rabbits.Methods LASIK or PRK was performed on one eye of each of 20 rabbits. One month later, 20µl of 0.5% timolol was instilled into the 10 LASIK eyes, 10 PRK eyes, and the 20 control contralateral eyes. One hour later, 150µl of aqueous humor was collected from all eyes, and the concentration of timolol in the aqueous humor was measured by high-performance liquid chromatography. The effect of LASIK and PRK on the corneal permeability to timolol was analyzed.Results The average timolol concentrations in the aqueous humor of the ten eyes 1 month after LASIK and in the ten contralateral eyes were 1.16 ± 0.58µg/ml and 1.07 ± 0.39µg/ml (average ± SD, P = 0.678), respectively. The average timolol concentrations in the aqueous humor of the ten eyes 1 month after PRK and in the ten contralateral eyes were 1.24 ± 0.43µg/ml and 1.12 ± 0.30µg/ml (P = 0.483), respectively. The average ratio of timolol concentration in the aqueous humor of the LASIK or PRK eyes 1 month after surgery to that of the contralateral normal eyes was 1.18 ± 0.58 or 1.19 ± 0.67 (P = 0.972), respectively.Conclusions LASIK and PRK do not affect corneal permeability to timolol 1 month after surgery. Jpn J Ophthalmol 2005;49:12–14 © Japanese Ophthalmological Society 2005     

Brain natriuretic peptide: identification of a second natriuretic peptide in human aqueous humour

AIMS/BACKGROUND—To measure aqueous humour levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in humans. To compare peptide levels in glaucomatous and control eyes to test the hypothesis that these peptides are increased in glaucoma. BNP and ANP are cyclic endopeptides whose principal biological effects are natriuresis and vasodilatation. Experimental glaucoma in animal models results in elevated aqueous ANP. Intravenous ANP administration in both animals and humans causes lowering of intraocular pressure (IOP). There are equivocal data to support a role for ANP in IOP regulation in human eyes. There are as yet no published data on BNP in human aqueous humour.
METHOD—This was a case-control study. Cases were primary open angle, pseudoexfoliation, and mixed mechanism glaucoma eyes undergoing trabeculectomy. Controls were cataract extraction eyes. There were 47 trabeculectomy eyes (44 patients) and 47 cataract extraction eyes (46 patients) matched for age, sex, race, systemic medications, and type of anaesthetic. 100-200 µl of aqueous humour were aspirated by paracentesis as the first step in the surgical procedure. Peptide levels were later measured by radioimmunoassay.
RESULTS—The presence of BNP and ANP in human aqueous humour was confirmed. BNP was present in higher concentrations than ANP. BNP levels tended to be greater in control eyes—glaucoma median 56.5 (range 0-3526.5) pg/ml versus control median 65.16 (range 0-1788) pg/ml (Wilcoxon signed rank test p = 0.78). ANP levels tended to be greater in glaucoma eyes than in controls: glaucoma median 3 (range 0-68.5) pg/ml versus control median 0 (range 0-60) pg/ml (Wilcoxon signed rank test p = 0.82). ANP and BNP were log linearly related in both groups (r glaucoma group = 0.961, r control group = 0.894).
CONCLUSION—This is the first report of BNP and ANP in human aqueous humour. Peptide levels did not differ significantly between glaucoma and cataract extraction eyes. A linear relation between log BNP and ANP was found. Further studies are required to clarify the role of these peptides in aqueous humour production and IOP regulation.

Keywords: brain natriuretic peptide; aqueous natriuretic peptide; aqueous humour; glaucoma     

Intraocular effects of substance P in the rabbit

The intraocular effects of substance P (SP) were studied in rabbits by measuring the pupil diameter, intraocular pressure (IOP), and aqueous humor protein concentration. Most of the animals were pretreated with indomethacin to avoid any interaction with prostaglandins. Intracameral injection of 1 to 150 ng of SP caused strong and persistent miosis without appreciably affecting the aqueous humor protein concentration or IOP. Intracameral injection of 0.8 to 11 micrograms of SP also induced an increase in IOP (7 to 8 mm Hg) without any apparent concomitant disruption in the blood-aqueous barrier. Outflow facility of aqueous humor decreased by a mean value of 50% after intracameral injection of 0.8 to 1.5 microgram of SP. Since the increase in IOP could be prevented by iridectomy, it was probably caused by a pupillary block from the intense miosis induced by SP. No disruption in the blood-aqueous barrier could be detected after intra-arterial infusion of 10 micrograms of SP or intravitreal injection of 100 ng of SP, indicating that the ciliary epithelium was practically insensitive to exogenous SP. Topical as well as subconjunctival administration of up to 1 mg of SP did not cause any irritative response in the eye. The results show that with concentrations of SP causing intense miosis, the eye does not exhibit visible hyperemia and disruption of the blood-aqueous barrier. This finding is consistent with the hypothesis that after certain irritative stimuli, miosis is mediated by a pathway separate from the hyperemia and disruption of the blood-aqueous barrier.     

The Effect of the Corneal Epithelium on the Intraocular Penetration of Fluoroquinolone Ophthalmic Solution

Purpose Pharmacokinetic studies of antibacterial agents for infectious eye diseases have usually been performed on normal rabbit eyes. In this study, the intraocular penetration of fluoroquinolone ophthalmic solutions was determined in normal rabbit eyes and in rabbit eyes that had the corneal epithelium intentionally removed.Methods We determined the intraocular penetration of ofloxacin (OFLX), levofloxacin (LVFX), and norfloxacin (NFLX), fluoroquinolone ophthalmic solutions that are already on the market and undergoing clinical studies, by injecting 50µl of each solution into the cul-de-sacs of rabbit eyes three times at 15-min intervals. The drug concentration at 10, 30, 60, 120, and 240min after final instillation was determined by high-performance liquid chromatography.Results The maximum concentration in the aqueous humor of normal rabbit eyes was 2.09 ± 1.56µg/ml (60min, OFLX), 2.57 ± 1.00µg/ml (30min, LVFX), and 0.42 ± 0.12µg/ml (120min, NFLX). The drug concentration in the aqueous humor of eyes with intentionally removed corneal epithelium was 12.50 ± 5.62µg/ml (30min, OFLX), 9.02 ± 2.45µg/ml (60min, LVFX), and 8.54 ± 5.17µg/ml (30min, NFLX). The drug penetration of the eye drops into eyes with removed corneal epithelium was around 6 times (OFLX), 3.5 times (LVFX), and 20 times (NFLX) higher than the penetration into the eye with normal cornea.Conclusion Among the pharmacokinetic parameters of the three ophthalmic solutions according to the one-compartment model, the maximum concentration in the aqueous and the area under the concentration–time curve in the aqueous tended to be higher in the eyes with intentionally removed corneal epithelia than in those with normal corneas. Jpn J Ophthalmol 2004;48:93–96 © Japanese Ophthalmological Society 2004     

Effect of Prostaglandin E2 on aqueous humor flow in the rabbit eye

Summary The examinations were carried out in albino rabbits under urethane anaestesia. After intracameral injection of 0.5 g Prostaglandin E₂, dissolved in 10 l 10% ethanol, intraocular pressure increased by 20.5±4.9 mm Hg. Aqueous humor protein concentration in the uninjected control eyes was 0.176±0.03 g%. Thirty minutes after intracameral injection of 10 l 10% ethanol solution the concentration rose to 0.38±0.19 g-%, and after of 0.5 g Prostaglandin E₂ to 1.85 ±0.41 g% These interventions were not followed by significant changes in aqueous humor osmolarity (normal value 313.7±17.9 mOsm, after ethanol 330 5±18. 0, and after prostaglandin E₂ 329.3±6.9).In a special series of experiments the rate of aqueous humor production was determined. In the uninjected control eyes a value of 1.57±0.61 l/min was found, but after intracameral injection of 0.5 g prostaglandin E₂, 5.45±1.99 l/min.The authors draw the conclusion that prostaglandin E₂ increases intraocular tension not by enhancing aqueous humor production but by disrupting the bloodaqueous humor barrier.

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Zusammenfassung Die Untersuchungen wurden an Albinokaninchen in Urethannarkose durchgeführt. Nach Injektion von 0,5 g Prostaglandin E₂ (in 10 l10%iger Äthanollösung) in die Vorderkammer stieg der Augenbinnendruck um 20,5±-4,9 mm Hg an. Der Gesamteiweißgehalt im Kammerwasser der intakten Kontrollaugen betrug 0,176±0,03 g-%. 30 min nach Einspritzung von 10 l 10%iger Äthanollösung in die Vorderkammer erhöhte sich der Gesamteiweißgehalt auf 0,38±0,19 g-%. Diese Einwirkungen hatten keine signifikante Änderung der Kammerwasser-Osmolarität zur Folge (Normalwert 313,7±17,9 mOsm, nach Äthanol 330,5±18,1 und nach Prostaglandin E₂ 329,3±6,9).In einer besonderen Versuchsreihe wurde die Kammerwasserproduktion bestimmt. In den intakten Kontrollaugen ergab sich hierbei ein Wert von 1,57±0,61 (l/m, nach Gabe von 0,5 g Prostaglandin E₂ aber 5,45±1,99 l/min.Die Autoren ziehen den Schluß, daß Prostaglandin E₂ den Augenbinnendruck nicht durch Steigerung der Kammerwasserproduktion, sondern durch Schädigung der Blut-Kammerwasserschranke erhöht.

     

Dynamic contour tonometry versus Goldmann applanation tonometry: a comparative study

Background Various sources of error, including central corneal thickness (CCT) and structural corneal rigidity, have been proposed for Goldmann applanation tonometry (GAT). The Pascal dynamic contour tonometer (DCT) is a novel device designed for intraocular pressure (IOP) measurements assumed to be largely independent of CCT and corneal curvature. We compared DCT with GAT in eyes with normal corneas of various thickness.Methods We prospectively measured IOP using DCT and GAT in random order in 100 eyes of 100 subjects (M:F=46:54; mean age 42±19, range 23–88 years).Results Mean DCT values were about 1mmHg higher than GAT readings (16±3 vs 15±3 mmHg, p=0.001). Bland–Altman analysis of individual pairs of DCT and GAT measurements revealed a bias of –1.0 mmHg [95% confidence interval (CI): ±1.2]. Neither GAT nor DCT showed a significant correlation with CCT (533±48, range 399–641 m).Conclusions In eyes with normal corneas, DCT allows suitable and reliable IOP measurements which are in good concordance with GAT. Comparison of DCT with intracameral manometry is desirable in the future.