The effect of prostaglandin inhibitors on the laser-induced disruption of the blood aqueous barrier in the rabbit

In four series, each containing five pigmented rabbits, the therapeutic effects of different anti-inflammatory agents on the laser-induced disruption of the blood aqueous barrier was investigated. Utilizing an argon laser, the peripheral iris of the left eye of each animal was coagulated with a total energy input of 1,000 mJ. The right eyes served as controls. After the coagulation the intraocular pressure was monitored at intervals of 10 min, and the anterior chamber was tapped for analysis of the aqueous humour 100 min after treatement. In a fifth group of five rabbits, aqueous humour was analysed without laser or drug treatment. The protein concentration and the activity of the lactate dehydrogenase were analysed in all samples of aqueous humour. A significant effect on the protection of the blood aqueous barrier could be identified in the eyes pre-treated with indomethacin (2 mg/kg body weight, injected intramuscularly), and in those pre-treated with dexamethasone (12.8 mg/kg body weight, injected intravenously;P < 0.025%). Pre-treatment with aspirin (20 mg/kg body weight, injected intravenously) also had a protective response in the eyes treatet by laser. The significance of the results of clinical treatment is outlined.     

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.     

The effect of yag laser iridotomy on the blood aqueous barrier in the rabbit

The effect of YAG laser iridotomy on the blood aqueous barrier in the rabbit was investigated in 21 eyes. In seven series, each containing three pigmented rabbits, the right eye received a YAG laser iridotomy in the upper nasal quadrant of the peripheral iris under standardized conditions utilizing the Mikroruptor II (Lasag Company, Thun/Switzerland). One of the parameters describing the blood aqueous barrier effects was the intraocular pressure, which was monitored at 10 min intervals. The iridotomy caused significant pressure increases in the treated eyes which was maintained up to 90 min following the laser procedure. The measurement of the protein concentration and the lactate dehydrogenase activity was done at equal time intervals after the iridotomy, on the basis of anterior chamber tapping of the treated eyes and the untreated control eyes. Over a period of 100 min after laser surgery, a positive correlation between time and protein concentration for the treated eyes (r = + 0.86) could be established. The activity of the enzyme lactate dehydrogenase in the treated eyes was increased within 5 min of the trauma, reaching a maximum 45 min after surgery, and the increase in activity level remained 150 min after surgery. The results indicate that the disturbance of the blood aqueous barrier with the YAG laser is not essentially different from that of the argon laser, although tissue damage may be more pronounced.     

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 effect of timolol maleate on the disruption of the blood-aqueous barrier in the rabbit eye

A disruption of the blood-aqueous barrier in rabbit eyes was elicited by use of topical prostaglandin E2(PGE2), infrared irradiation of the iris, or by subcutaneous alpha-melanocyte-stimulating hormone (alpha-MSH). The aqueous flare provoked was measured quantitatively with a photoelectric instrument. The effect of the (topical) beta-adrenergic antagonist timolol maleate on the breakdown of the blood-aqueous barrier was tested. Timolol applied topically in very large doses had no effect on exogenously administered PGE2. However, even in a very small concentration applied topically, timolol reduced the flare response to both infrared irradiation and alpha-MSH. These results support the theory that the effect of alpha-MSH and infrared irradiation on the blood-aqueous barrier is dependent on intact beta-adrenergic receptor sites.     

Blood-aqueous barrier disruption in experimental anterior segment ischemia in rabbit eyes

The blood-aqueous barrier (BAB) in experimentally induced anterior segment ischemia (ASI) following strabismus or retinal detachment surgery in pigmented rabbits was evaluated by laser flare photometry. Four simultaneous rectus tenotomies produced a significantly higher flare value on the 1st postoperative day. Obstruction of one or two vortex veins produced significantly high flare values on the 1st and 3rd postoperative days. Scleral buckling with interference of one vortex vein produced a higher flare value than that with buckling alone. Interference of three vortex veins by diathermy and the encircling procedure produced serious ASI. Disruption of BAB in ASI can be detected quantitatively with laser flare photometry. Introduction of prostaglandin synthetase inhibitor resulted in a significant reduction of flare values following surgery. Prostaglandin synthetase inhibitor can partly ameliorate BAB disruption.     

The effect of viscoelastic substances on postsurgical blood aqueous barrier

A postsurgical flare was evaluated with a flare-cell meter and the effect of residual viscoelastic substances on the blood aqueous barrier function was studied. The materials consisted of 100 eyes undergoing extracapsular cataract extraction and posterior chamber lens implantation using sodium hyaluronate products (Healon:Pharmacia and Opegan:Santen). The molecular weight is 1.9-3.6 million daltons in Healon and 0.9-1.2 million daltons in Opegan. According to the aqueous warm current on the 1st postoperative day, the eyes were divided into two groups; the poor current group and the normal current group. The poor current group consisted of 13 eyes had static aqueous current, probably due to residual viscoelastic substances from the clinical findings, namely a little pain, foggy general corneal edema and spontaneous recovery of the warm current without specific administrations of antibiotics. Eyes with poor current were recognized in 18% (11/62) among cases with Healon and 5% (2/38) in case with Opegan. Flare values of the poor current group were higher in 7 eyes than the highest of the normal current group on the 1st postoperative day. After the 2nd postoperative day, the median flare value of the poor current group was higher than that of the normal current group. The difference was statistically significant throughout the first week (p less than 0.02). The cell number was also higher in the poor current group on the 1st and 2nd postoperative day (p less than 0.02). These findings suggest that the residual viscoelastic materials may increase the breakdown of blood-aqueous barrier and/or interfere the barrier recovery.     

The site of action of prostaglandin E2 on the disruption of the blood-aqueous barrier in the rabbit eye

The protein content of the anterior chamber and posterior chamber was determined soon after trauma to the eye. The trauma was topical administration of prostaglandin E₂ or paracentesis of the anterior chamber in untreated rabbits or rabbits treated with aspirin. The results are consistent with the hypothesis that the site of action of prostaglandin E₂ is on the tight junctions of the non-pigmented epithelial cells of the ciliary body. The possible routes of flow of plasmoid aqueous humor into the anterior chamber after trauma is discussed.     

Continued breakdown of the blood aqueous barrier following cataract surgery.

Following routine extracapsular cataract and posterior chamber implant surgery, recovery of the blood aqueous barrier (BAB) was quantified by sequential anterior chamber fluorophotometry. This was correlated with surgical details and postoperative findings to ascertain those factors which were related to excessive damage of the BAB immediately after surgery and to failure to recover a normal BAB by 3 months postoperatively. A cohort of 84 patients was followed. In the early postoperative period excessive levels of damage to the BAB were related to iris damage (p < 0.01) and diabetes mellitus (p < 0.01). By 3 months, 79% of the eyes had recovered normal BABs and 21% (18 eyes) had persisting excessive fluorescence which correlated with an abnormal pupil shape (p < 0.02) and the development of posterior synechiae (p < 0.001).     

Development of laser-induced retinal damage in the rabbit

 · Background: Laser lesions may induce retinal damage that is larger than expected from the size of the coagulated area. This study was designed to follow the development of laser-induced reduction in retinal function and to correlate it with structural changes. · Methods: Pigmented rabbits were treated in one eye with 225 argon laser lesions. The ERG responses were recorded at different times after treatment. The effect of the laser treatment upon the functional integrity of the retina was assessed from the ERG responses. Structural damage was examined by light microscopy. · Results: Shortly (1–2 h) after laser treatment, the ERG responses were reduced by about 50%. ERG deficit continued to develop and reached a maximal level about 24 h after treatment. Thereafter, slow recovery was observed but permanent deficit, relative to the initial laser effect, was seen even 30 days after treatment. Histological observations indicated extensive serous retinal detachment between laser lesions that developed within 24 h after treatment. At 30 days post-treatment, lesioned areas were completely destroyed and heavily pigmented. The retina between lesions was attached to the pigment epithelium but exhibited different degrees of structural damage. · Conclusions: The immediate laser damage is confined to the coagulated areas while secondary functional damage develops within 24 h and probably reflects serous retinal detachment between lesions. The serous retinal detachment completely resolves with time but may induce permanent structural abnormalities in non-coagulated retinal areas that is reflected in a functional deficit larger than the initial laser effect. Received: 9 December 1998 Revised version received: 1 March 1999 Accepted: 2 March 1999     

Role of Tromaril as anti-prostaglandin drug on blood aqueous barrier

In this experimental work, it was observed that after anterior chamber paracentesis there was more effusion of protein into the anterior chamber. Pretreatment with aspirin/indomethacin and a new drug, enfenamic acid (Tromaril), decreased this trauma-induced increase in aqueous protein content. It was further observed that this inhibition was more marked with Tromaril pretreatment in comparison with other drugs. Prostaglandin-mediated disruption of blood aqueous barrier can also be decreased with Tromaril pretreatment. Tromaril, a prostaglandin synthetase inhibitor, may help us to control the reactions to surgical ocular trauma and other ocular inflammatory diseases.     

Effects of subconjunctival methylprednisolone on the blood aqueous barrier following cataract surgery

The aim of this double-blind randomized study was to assess the effect of subconjunctival methylprednisolone hemisuccinate (MH) on the recovery of the blood aqueous barrier (BAB) following uncomplicated cataract surgery performed by the same surgeon in normal eyes. Fifty eyes of fifty patients (28 female, 22 male, mean age 72.3 ± 11.2 years) were randomized into two groups: group 1 received a subconjunctival injection of MH (40 mg in 0.5 cc) at the end of the surgery and group 2 did not. All patients were free of other ocular or systemic diseases known to alter the BAB and were not taking any anti-inflammatory medications. Postoperative treatments were similar in both groups. The patients were submitted to laser flare photometry 30 minutes to one hour after mydriasis with a drop of tropicamide preoperatively and on the first, second and seventh day and then one month and six months following surgery. No difference in aqueous flare was seen between the two groups on any of postoperative visits. These data suggest that subconjunctival MH has no beneficial effect in postoperative BAB permeability following uncomplicated cataract surgery in normal eyes.Presented in part at ARVO Meeting 1994 (Sarasota, Florida, USA)     

Effects of anterior chamber irrigation and irrigating solutions on the blood aqueous barrier

Anterior chamber irrigation and irrigating solutions were evaluated for their possible damaging effects on the blood-aqueous barrier. Rabbit anterior chamber was irrigated with physiological saline, lactated Ringer solution, balanced salt solution (BSS) and S-MA2 using the irrigation aspiration tip of Cavitron Kelman phacoemulsifier. Fluorophotometry was performed to evaluate the function of the blood-aqueous barrier. Physiological saline yielded the most severe damage, and lactated Ringer solution and BSS yielded moderate damage in blood aqueous barrier, while S-MA 2 showed only slight damage to barrier function. These results suggest that HCO^–3 and glucose, as well as Ca⁺⁺, Mg⁺⁺ and the buffer system, are essential constituents for maintaining function in the blood-aqueous barrier.     

The anatomy of the rabbit aqueous outflow pathway

The morphology of the filtration angle and pathway of aqueous outflow was studied in 10 pigmented rabbits using light and electron microscopic techniques. The following conclusions were arrived at: Numerous pectinate ligaments were found to cross the rabbit filtration angle. However, large spaces between these ligaments allows aqueous access to the peripheral portion of the angle and then to the trabeculum. The drainage of aqueous filtered through the meshwork is served by a plexus of 1 to 4 channels, which contain giant vacuoles along their internal and external walls. A single layer of endothelial cells was found covering all meridians of the entire trabeculum from the termination of the cornea to the filtration angle recess. This layer, here termed the trabecular endothelial layer, is a continuation of the corneal endothelium, and it is accompanied by the posterior limiting lamina (Descemet's membrane) for its full length. The aqueous passes through the trabecular endothelial layer by an intracellular route that possibly requires energy. The presence of the trabecular endothelial layer in the rabbit may explain the variation that is known to exist between human and rabbit in responses to pharmaceutical agents. The physiology of the rabbit trabecular endothelial layer needs to be investigated to determine the suitability of this species as an animal model for the human glaucomatous conditions caused by the presence of such a layer.     

Effect of indomethacin and prednisolone on the disruption of the blood-aqueous barrier after hyperthermia on the rabbit eye by focused ultrasound

In 24 rabbits both eyes were treated in the perilimbic area with hyperthermia by focussed ultrasound at a frequency of 4.65 MHz. The intra-ocular pressure (IOP) decreased significantly in all eyes. The effect of pre-treatment with indomethacin and prednisolone on the inflammatory response induced by the insonification was assessed by determination of protein in the aqueous humour 2 h after ultrasound treatment. Local pre-treatment with indomethacin but not with prednisolone was followed by less increase in protein concentration of the aqueous humour as compared to placebo-treated controls. The IOP was not influenced significantly by the drug pre-treatments.     

Fluorophotometry as a method for the detection of permeability changes in the blood and aqueous humor barrier

The increase in permeability of the blood-aqueous barrier after Nd-YAG laser iridotomy and the protective effect of locally applied indomethacin were investigated in an experimental animal study using a computerized fluorophotometer. The permeability of the blood-aqueous barrier was evaluated by three different molecules: fluorescein-sodium (molecular weight 330), fluorescein-labeled dextran 70 000 (molecular weight 70 000) and fluorescein-labeled dextran 150 000 (molecular weight 150 000). The fluorescein concentration of the anterior chamber was measured in 36 eyes (18 rabbits) as well as in a control group of 9 eyes (9 rabbits) at fixed times after intravenous dye injection. Fluorescein leakage occurred, but no leakage of fluorescein-labeled dextrans was visible in the control group. Laser iridotomy induced a time-dependent increase in anterior segment permeability to fluorescein and fluorescein-labeled dextrans. Disturbance of the blood-aqueous barrier was effectively reduced by topical pretreatment with indomethacin, which mainly inhibited the leakage of the fluorescein-labeled dextrans. The clinical relevance of the laser-induced breakdown of the blood-aqueous barrier and the protective effect of a prophylactic pharmacotherapy are discussed.     

Diode laser-induced mitosis in the rabbit retinal pigment epithelium.

BACKGROUND AND OBJECTIVE: The induction of retinal pigment epithelium (RPE) proliferation without damaging the inner layers of the retina might be helpful in patients with RPE atrophic changes and degeneration. This study aimed to induce mitosis in the RPE of the rabbit after subthreshold photocoagulation with the diode laser. MATERIALS AND METHODS: Twenty-five male Dutch rabbits received retinal photocoagulation using an 810-nm diode laser with different power settings and exposure times. The eyes were processed for light microscopy, electron transmission microscopy, and immunohistochemistry. RESULTS: Neither morphological alterations nor mitotic activity was found after 5-mJ energies. Retinal layers were not affected and RPE hyperplasia appeared in the treated areas associated with mitotic activity when 10 mJ was used. Mitosis induction and retinal damage appeared with 20, 50, and 100 mJ and were associated with ophthalmoscopic damage. CONCLUSIONS: The use of subthreshold 810-nm diode laser treatment may induce mitosis in the RPE without causing damage to the neighboring layers.