Interaction of adrenergic agents with alpha-melanocyte-stimulating hormone and infrared irradiation of the iris in the rabbit eye.

Breakdown of the blood aqueous barrier in the rabbit eye induces a protein leakage into the aqueous humor, seen as a flare in the anterior chamber. A barrier damage was induced by topical prostaglandin E2(PGE2), infrared irradiation of the iris, or alpha-melanocyte-stimulating hormone (alpha-MSH) given subcutaneously. The aqueous flare was measured quantitatively by means of a photoelectric instrument. The interference of adrenergic antagonists and agonists on the breakdown of the barrier was tested. The alpha-adrenergic antagonist phentolamine and the beta-adrenergic antagonist propranolol, given intravenously, had no effect on exogenously administered PGE2, but both antagonists reduced the flare response to infrared irradiation which is supposed to exert its effect via endogenous prostaglandin release. The alpha-MSH response was unaffected by phentolamine, whereas propranolol abolished the flare response to alpha-MSH totally. The PGE1 response was unaffected both by the alpha-adrenergic agonist noradrenaline and the beta-adrenergic agonist terbutalin sulfate, administered topically. Noradrenaline, however, inhibited the flare response to infrared irradiation and facilitated the flare response to alpha-MSH. Terbutalin sulfate worked synergistically with both infrared irradiation and alpha-MSH. It is assumed that alpha-MSH exerts its effect on the barrier via enhanced beta-adrenergic activity, whereas the effects caused by infrared irradiation seem conditioned by intact alpha- as well as beta-adrnergic receptor sites.     

The effect of experimental uveitis on the uptake of prostaglandin E1 in the rabbit iris-ciliary body

Disruption of the blood-aqueous barrier in rabbits was elicited by infrared irradiation of the iris or by alpha-melanocyte stimulating hormone (alpha-MSH) given subcutaneously. One group of animals was pretreated with topical imidazole before the injection of alpha-MSH. The aqueous flare response was followed and the rabbits were killed at the expected height of the uveitis. The uptake of 3H-prostaglandin E1 in the iris with the ciliary body was then determined and found to be significantly decreased in the rabbits in which alpha-MSH had caused a severe damage of the blood-aqueous barrier. When alpha-MSH caused a more moderate aqueous flare response the prostaglandin uptake was on the contrary significantly increased. Pretreatment of the animals with topical imidazole enhanced parallelly the prostaglandin uptake and the aqueous flare response to alpha-MSH. Topical imidazole per se was found to increase the accumulation of prostaglandin. The prostaglandin uptake values were, however, unchanged in eyes in which infrared irradiation of the iris induced a moderate flare response.     

The effect of theophylline on the breakdown of the blood-aqueous barrier in the rabbit eye.

A disruption of the blood-aqueous barrier in rabbit eyes was elicited by topical prostaglandin E2, infrared irradiation of the iris, or subcutaneous alpha-melanocyte stimulating hormone (alpha-MSH). The course of the inflammatory reaction was followed by photoelectrical measurements of the aqueous flare in the anterior chamber. Pretreatment with intravenous theophylline, a phosphodiesterase inhibitor, significantly increased the protein leakage caused by prostaglandin E2 and alpha-MSH, but the response to infrared irradiation was slightly but not significantly enhanced. Intravenous theophylline given in higher doses caused per se an aqueous flare increase, which could not be inhibited by pretreatment with topical indomethacin. Our results indirectly indicate that accumulation of intraocular cAMP promotes a barrier damage and that cAMP might be the common effector of the barrier breakdown caused by prostaglandin as well as by nonprostaglandin agents.     

Capsaicin pretreatment prevents disruption of the blood-aqueous barrier in the rabbit eye

Capsaicin, the irritating agent of red pepper, produces ocular inflammation through a neurogenic mechanism. The present study is concerned with the long-term effects of capsaicin pretreatment on the capacity of the eye to respond to different inflammatory stimuli. Following retrobulbar injection of capsaicin to rabbits the aqueous flare response induced by subsequent infrared irradiation (IR) of the iris, subcutaneously administered alpha-melanocyte-stimulating hormone (alpha-MSH) and exogenously administered prostaglandin E2 (PGE2) was reduced greatly. In the case of IR and alpha-MSH the reduced responsiveness was manifest for several weeks after capsaicin pretreatment, involving first the capsaicin-treated eye, but later also the contralateral control eye. After 2-3 months the aqueous flare response was normal in both eyes. In the case of PGE2 the responsiveness was reduced for a shorter time; after 3 weeks the response was normal in both eyes. The results indicate that all three stimuli tested are at least partly dependent upon an intact sensory innervation to disrupt the blood-aqueous barrier, but that the mechanism of action of PGE2 is different from that of IR and alpha-MSH.     

The effects of 3-isobutyl-methyl-xanthine on experimentally induced ocular inflammation in the rabbit

The effect of topical administration of 3-isobutyl-methyl-xanthine (IBMX), a potent phosphodiesterase inhibitor, was studied on an experimentally provoked uveitis in rabbits. After presensitization with an intravitreal injection of human serum albumin (HSA), intravenous antigenic challenge induces blood-aqueous barrier breakdown and leukocyte infiltration. The effect of IBMX on the blood-aqueous barrier was determined by scoring the severity of the flare in the anterior chamber and by determination of the levels of ascorbic acid and protein in the aqueous. Treatment with IBMX 1% two times daily, significantly inhibited the breakdown of the blood-aqueous barrier and the increase in PGE2 level of the aqueous humor. There was no effect on leukocyte infiltration. The therapeutic effect of IBMX in blood-aqueous barrier protection is comparable with the effect of topical treatment with the corticosteroid medrysone.     

The effect of polyphloretin phosphate on the aqueous flare response to alpha-melanocyte stimulating hormone

The breakdown of the blood aqueous barrier caused by topical prostaglandin E1 (PGE1), prostaglandin E2 (PGE2) or subcutaneous alpha-melanocyte stimulating hormone (alpha-MSH) was quantified by measurements of the aqueous flare seen in the anterior chamber. Polyphloretin phosphate (PPP) administration subcutaneously was found to effectively block the protein leakage caused by all three traumatic stimuli. The same dose of PPP given intravenously inhibited effectively the flare response to PGE1 and alpha-MSH, whereas the effect of PGE2 was only slightly decreased. Significant inhibition by subconjunctival PPP was not achieved for any of the three stimuli. Assuming that PPP is a specific PG-antagonist the present results support the eariler suggestion that PGs take part in the barrier damaging action of alpha-MSH. However, it cannot be excluded that PPP acts on a step subsequent to PG. This step might be common to PGs- and alpha-MSH-effects on the barrier, explaining why PPP inhibits both types of trauma.     

Effects of tetramethylpyrazine on prostaglandin E(2)- and prostaglandin E(2) receptor agonist-induced disruption of blood-aqueous barrier in pigmented rabbits

PURPOSE: To evaluate the effect of tetramethylpyrazine on the elevation of aqueous flare and intraocular pressure (IOP) induced by prostaglandin (PG) E(2) and PGE(2) receptor (EP) agonists. METHODS: PGE(2) or EP agonists (11-deoxy PGE(1), EP(2) agonist; 17-phenyl trinor PGE(2), EP(1) and EP(3) agonist; or sulprostone, EP(1) and EP(3) agonist), 25 microg/mL, were transcorneally administered to pigmented rabbits. Animals were pretreated with tetramethylpyrazine intravenously (10 or 30 mg/kg) or topically (0.1% solution). Aqueous flare was measured using a laser flare-cell meter, and the intensity was expressed as the area under the curve (AUC). Intraocular pressure was measured using a noncontact tonometer. RESULTS: After administration of PGE(2), aqueous flare and IOP increased and then gradually decreased. The AUC of eyes pretreated with tetramethylpyrazine, 10 or 30 mg/kg, intravenously, or topical 0.1% solution, was significantly smaller than that of the controls. The mean Delta IOP of eyes pretreated with tetramethylpyrazine, 30 mg/kg intravenously, was significantly lower than that of the controls. After administration of 11-deoxy PGE(1), aqueous flare increased and then gradually decreased. 17-phenyl trinor PGE(2) and sulprostone did not disrupt the blood-aqueous barrier. The AUC of eyes pretreated with tetramethylpyrazine, 10 or 30 mg/kg, intravenously, before 11-deoxy PGE(1) application was significantly smaller than that of the controls. CONCLUSION: The results indicated that tetramethylpyrazine inhibited PGE(2)- or 11-deoxy PGE(1)-induced elevation of aqueous flare and IOP.     

Effect of topical betaxolol on acute rise of aqueous flare induced by prostaglandin E(2) in pigmented rabbits.

PURPOSE: To evaluate the effects of topical betaxolol on experimental ocular inflammation. METHODS: Transcorneal diffusion of 25 microg/mL (7.09 x 10(-2) mmol/L) of prostaglandin E(2) (PGE(2)), placed in a glass cylinder, was employed to induce aqueous flare elevation in pigmented rabbits. Betaxolol was administered topically before PGE(2) application. Aqueous flare was measured with a laser flare cell meter. RESULTS: Four-, two-, and one-time topical instillations of betaxolol inhibited the PGE(2)-induced aqueous flare elevation by 44% +/- 8%, 32 +/- 7%, and 8 +/- 6%(mean +/- SD), respectively. The inhibition of flare elevation was dependent on the number of betaxolol instillations. CONCLUSION: Topical betaxolol has an inhibitory effect on PGE(2)-induced aqueous flare elevation in rabbit eyes.     

Comparison of the effects of corticosteroids and indomethacin on the response of the blood-aqueous barrier to injury

Aqueous protein content was estimated as a measure of the integrity of the blood-aqueous barrier after paracentesis or argon laser photo-coagulation of the iris in rabbits. Corticosteroid pretreatment topically or by subconjunctival or intramuscular injection exerted only a moderate inhibitory effect on the breakdown of the blood-aqueous barrier. Instillation of 0.1% indomethacin however, strongly inhibited the response in both models. The results are indicative of the potential usefulness of topical administration of prostaglandin synthetase inhibitors in the treatment of non-infectious inflammatory diseases.     

Effects of isopropyl unoprostone, latanoprost, and prostaglandin E(2) on acute rise of aqueous flare in pigmented rabbits

PURPOSE: To evaluate the effect of isopropyl unoprostone, latanoprost, and prostaglandin E(2) (PGE(2)) on aqueous flare elevation. METHODS: Isopropyl unoprostone (0.12%) or latanoprost (0.005%) was topically instilled. Transcorneal diffusion of PGE(2), 25 microg/ml, using a glass cylinder, was achieved in pigmented rabbits. Aqueous flare was measured with a laser flare cell meter. RESULTS: Topical instillation of isopropyl unoprostone induced aqueous flare elevation in rabbit eyes. Also, topical isopropyl unoprostone additionally induced aqueous flare elevation in eyes with transcorneal diffusion of PGE(2). Latanoprost did not induce flare elevation. CONCLUSION: Isopropyl unoprostone induced aqueous flare elevation in rabbits, and latanoprost did not produce aqueous flare elevation.     

Topical timolol and blood-aqueous barrier permeability to protein in human eyes]

The effect of topical 0.5% timolol on the permeability of the blood-aqueous barrier to plasma protein was studied in ten young normal volunteers. Before and after instillation of timolol in one eye, simultaneous measurements of aqueous flow rate, f(t), by fluorophotometry and protein concentration in the anterior chamber, Ca(t), with a laser flare-cell meter were made in both eyes at hourly intervals. The coefficient of protein entry into the anterior chamber was calculated using an equation formulating protein dynamics in the anterior chamber from the changes in f(t), Ca(t), and plasma protein concentration. The Ca(t) in the treated eye showed a maximum increase of 37 +/- 4% (mean +/- SEM) as compared with that in the fellow eye 5 hours after instillation, while the f(t) in the treated eye showed a maximum reduction of 30 +/- 4% 2 hours after instillation. The intraocular pressure in the treated eye showed a maximum reduction of 3.0 +/- 0.3 mmHg 2 hours after instillation. No significant changes were found in the coefficient of protein entry in the anterior chamber between before and after timolol instillation or between timolol-treated and fellow untreated eyes. These results indicated that topical 0.5% timolol does not affect the permeability of the blood-aqueous barrier to plasma protein significantly.     

Comparison of diclofenac and fluorometholone in preventing cystoid macular edema after small incision cataract surgery: a multicentered prospective trial

PURPOSE: To compare a nonsteroidal topical solution (0.1% diclofenac) to a steroidal topical solution (0.1% fluorometholone) in preventing cystoid macular edema (CME) and disruption of the blood-aqueous barrier. METHODS: A multicentered, prospective clinical trial was performed on eyes undergoing phacoemulsification followed by implantation of a foldable acrylic intraocular lens by the envelope technique. The presence and degree of cystoid macula edema (CME) was determined by fluorescein angiography. A breakdown of the blood-aqueous barrier was determined by laser flare-cell photometry. RESULTS: Five weeks after surgery, CME was present in 3 of 53 eyes (5.7%) receiving diclofenac and in 29 of 53 eyes (54.7%) receiving fluorometholone. This difference was statistically significant (P < .001). The amount of flare in the anterior chamber at 3 days, 1, 2, 5, and 8 weeks after surgery was also significantly lower (P < .01-P < .001) in the diclofenac group. The degree of flare at 3 days, 1, 2, 5, and 8 weeks after surgery was significantly higher in eyes with CME (P < .001). CONCLUSIONS: These findings suggest that diclofenac effectively prevents CME following cataract surgery and that CME is closely related to the breakdown of the blood-aqueous barrier.     

Effects of topical clonidine on prostaglandin-E(2)-induced aqueous flare elevation in pigmented rabbits

We evaluated the role of topical clonidine on experimental ocular inflammation. Transcorneal diffusion of prostaglandin (PG) E(2), 7. 09 x 10(-2) mmol/l, with the use of a glass cylinder was employed to produce aqueous flare elevation in pigmented rabbits. Clonidine was topically administered and yohimbine was injected intravenously. Aqueous flare was measured with a laser flare cell meter. Topical instillation of 0.25% clonidine inhibited 89% of PGE(2)-induced aqueous flare elevation. Instillation of clonidine at 60 or 30 min before and 10 min after PGE(2) inhibited flare significantly. Pretreatment with intravenous yohimbine decreased the clonidine-induced inhibition of the flare elevation in a dose-dependent manner. It is possible that the anti-inflammatory action of topical clonidine may be mediated partly by alpha(2)-receptors.     

The effect of topically applied prostaglandin inhibitors on the laser-induced disruption of the blood aqueous barrier

The therapeutic effect of topically applied prostaglandin inhibitors on the laser-induced disruption of the blood-aqueous barrier was investigated in six series of five rabbits each. One series was not coagulated and served as baseline, and in a reference group laser coagulation was performed without pretreatment with a prostaglandin inhibitor. In four series the iris laser coagulation of the left eyes was preceded by topical application of a prostaglandin inhibitor. The right eyes served as controls for the contralateral effect on the blood aqueous barrier. After laser coagulation the intraocular pressure was monitored at 10-min intervals, and the anterior chamber was tapped for analysis of the protein concentration and the lactate dehydrogenase activity. Pretreatment with dexamethasone eyedrops and indomethacin eyedrops markedly blocked the laser-induced disruption of the blood-aqueous barrier. The level of protein concentration in the aqueous humor after laser coagulation was much less after pretreatment with dexamethasone or indomethacin eyedrops. The effect was significant, both for the laser-treated eyes and for the noncoagulated fellow eyes (p < 0.025). The subconjunctival pretreatment with dexamethasone 1 or 24 h before laser coagulation had no significant effect with respect to the protection of the blood aqueous barrier.     

Effects of topical mydriatics and vasoconstrictors on prostaglandin-E2-induced aqueous flare elevation in pigmented rabbits

We evaluated the effects of topical instillation of mydriatics and vasoconstrictors on prostaglandin E2 (PGE2) induced aqueous flare elevation in pigmented rabbits. Transcorneal diffusion of PGE2 (25 microg/ml) by means of a glass cylinder produced aqueous flare elevation. Mydriatics (atropine sulfate, tropicamide, tropicamide plus phenylephrine hydrochloride, phenylephrine hydrochloride, and cyclopentolate hydrochloride) or vasoconstrictors (naphazoline nitrate and tramazoline hydrochloride) were topically administered before PGE2 application. Aqueous flare was measured with a laser flare-cell meter. One or two instillations of atropine sulfate 1.0%, tropicamide 0.4%, tropicamide 0.5% plus phenylephrine hydrochloride 0.5%, phenylephrine hydrochloride 5.0%, cyclopentrate hydrochloride 1.0%, and naphazoline nitrate 0.05% did not inhibit PGE2-induced aqueous flare elevation. Tramazoline hydrochloride 0.118% inhibited significantly (p < 0.05) PGE2-induced aqueous flare elevation. It is possible that vasoconstriction may be involved partly in inhibition of PGE2-induced aqueous flare elevation by some drugs in pigmented rabbits.     

Disruption of the blood-aqueous barrier following retinal laser photocoagulation and cryopexy in pigmented rabbits

Disruption of the blood-aqueous barrier (BAB) induced by retinal photocoagulation and cryopexy in pigmented rabbits was evaluated by laser flare photometry. A significant increase in flare values after retinal photocoagulation was measured from the 1st postoperative day, with values returning to baseline levels by day 7. Cryopexy induced consistently high flare values for 14 days. Intravitreal injection of interleukin (IL) 1, IL-6 and prostaglandin (PG) E(2) induced a significant increase in flare values. Following these treatments, introduction of a PG synthetase inhibitor can partially ameliorate BAB disruption. IL-1, IL-6 and PGE(2) may be involved in BAB disruption following retinal photocoagulation and cryopexy.     

超声乳化白内障吸除术对血-房水屏障功能的影响

目的　观察小切口超声乳化白内障吸除人工晶状体植入术及相关因素对血 房水屏障功能的影响。方法　使用激光蛋白细胞检测仪对 60例 (64只眼 )白内障患者超声乳化白内障吸除人工晶状体植入术前、后的房水蛋白浓度进行定量检测 ,记录并比较闪光值。术后随访时间为 3个月。结果　超声乳化白内障吸除人工晶状体植入术前 ,术后 1d、1周、1个月及 3个月术眼房水的平均闪光值分别为 (6 94± 0 3 4 )、(2 6 2 7± 1 3 7)、(13 96± 1 0 5)、(9 0 7± 0 43 )及 (7 16± 0 2 7)光粒子数 /ms ,其中术后 1d、1周及 1个月高于术前 ,且差异均有显著意义 (P <0 0 5) ;术后 3个月与术前比较 ,差异无显著意义 (P >0 0 5)。术后早期术眼房水蛋白浓度与患者年龄呈正相关 (r =0 40 0 ,P =0 0 0 1) ,与患者的性别和眼别均无相关。术中虹膜脱出者术后 1d和 1周血 房水屏障功能破坏严重。结论　超声乳化白内障吸除人工晶状体植入术在术后短期内影响术眼的血 房水屏障功能 ;激光蛋白细胞检测仪可动态评价超声乳化白内障吸除术对血 房水屏障功能的影响。 (中华眼科杂志 ,2 0 0 4,40 :2 6 2 9)     

Indomethacin and the epinephrine-induced breakdown of the blood-ocular barrier in rabbits

Using aqueous and vitreous fluorophotometry, the authors examined the blood-aqueous and blood-retinal barrier functions in three groups of pigmented rabbits. Epinephrine (1.25%) was applied topically five times daily and indomethacin (0.5% sesame oil suspension) was applied topically three times daily to one eye of each of the animals in Group 1; under the same regimen, epinephrine and indomethacin placebo were administered to one eye of each of the animals in Group 2 and epinephrine placebo and indomethacin placebo were administered to one eye of each of the animals in Group 3. Fluorophotometry was done 1, 2, and 3 months after drug administration. The results showed that epinephrine induced disruption of the blood-aqueous barrier 2 and 3 months after drug administration, and that the magnitude of this disruption increased with time. Epinephrine also induced disruption of the blood-retinal barrier 3 months after drug administration. Indomethacin significantly prevented disruption of the blood-aqueous barrier at 2 and 3 months and significantly prevented disruption of the blood-retinal barrier at 3 months. The magnitudes of the barrier disruptions in eyes treated with both epinephrine and indomethacin were slightly higher than, or the same as, those of the control eyes. The results strongly indicated that the epinephrine-induced disruption of the blood-ocular barrier was partially caused by prostaglandins and other cyclo-oxygenase products whose biosynthesis was initiated by epinephrine.     

Effects of topical antiglaucoma eye drops on prostaglandin E(2)-induced aqueous flare elevation in pigmented rabbits

PURPOSE: To evaluate the role of topical instillation of some antiglaucoma agents on experimental elevation of aqueous flare induced by prostaglandin E(2) (PGE(2)) in pigmented rabbits. METHODS: Transcorneal diffusion of PGE(2) (25 microg/mL or 7.09 x 10(-2) mM) with the use of a glass cylinder was achieved to produce aqueous flare elevation in pigmented rabbits. An antiglaucoma agent was topically administered before application of PGE(2). Aqueous flare was measured with a laser flare cell meter. RESULTS: A single instillation of apraclonidine 1.15%, two instillations of epinephrine 1.25%, two instillations of dipivefrin 0.1%, and two instillations and one instillation of dipivefrin 0.04% eye drops inhibited 98%, 96%, 87%, 73%, and 47% of PGE(2)-induced aqueous flare elevation, respectively. Timolol 0.5%, nipradilol 0.25%, dorzolamide 1%, and pilocarpine 2% eye drops had no effects on the increase of PGE(2)-induced flare. CONCLUSIONS: Apraclonidine, epinephrine, and dipivefrin eye drops inhibit PGE(2)-induced elevation of aqueous flare in pigmented rabbits.     

Effects of cyclic nucleotide analogs on intraocular pressure and trauma-induced inflammation in the rabbit eye.

In this study the effects of cell-permeable 8-bromo-cAMP and 8-bromo-cGMP on intraocular pressure (IOP) and puncture-induced inflammatory response were investigated. Both 8-bromo-cAMP and 8-Bromo-cGMP reduced IOP when given subconjunctivally, but not topically. Subconjunctival administration of 8-bromo-cAMP induced a moderate disruption of the blood-aqueous barrier (BAB); in addition, subconjunctival 8-bromo-cAMP, but not topical 8-bromo-cAMP or subconjunctival 8-bromo-cGMP, reduced the disruption of the BAB and elevation of the aqueous PGE2 level after puncture trauma. It is concluded that the effects of 8-bromo-cAMP depend on the mode of administration, since this determines the concentration of 8-bromo-cAMP reached in the aqueous humor. It is suggested that 8-bromo-cAMP can partially suppress a slight inflammatory response by interference with the release of arachidonic acid from the tissues surrounding the aqueous humor.