Pigmented Rabbit Eyes Research Articles

Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits.

To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy (PVR) and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma. Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus, followed by treatment with a slow-release dexamethasone implant (Ozurdex) or sham injection. Left eyes were used as normal controls. The intraocular pressure (IOP) was monitored using an iCare tonometer. PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk; specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction, Western blot, protein chip analysis, or immunofluorescence staining. During the observation period, PVR severity gradually increased. Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group. Ozurdex significantly alleviated PVR development and Müller cell gliosis. Post-traumatic inflammation fluctuated and was persistent. The interleukin-1β (IL-1β) mRNA level was significantly upregulated, peaking on day 3 and increasing again on day 21 after injury. The expression of nod-like receptor family pyrin domain containing 3 (NLRP3) showed a similar trend that began earlier than that of IL-1β expression. Ozurdex suppressed the expression of IL-1β, NLRP3, and phosphorylated nuclear factor-kappa B (NF-κB). The average IOP after treatment was within normal limits. The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk. Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis, and thus alleviates PVR severity. This study highlights the important role of IL-1β, and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1β inflammatory axis. In summary, Ozurdex provides a potential therapeutic option for traumatic PVR.

Potential Mechanisms of Intraocular Pressure Reduction by Micropulse Transscleral Cyclophotocoagulation in Rabbit Eyes.

PurposeTo evaluate the histological changes associated with, and the potential mechanisms of, intraocular pressure (IOP) reduction by micropulse cyclophotocoagulation (MP-CPC) in rabbit eyes.MethodsMP-CPC was performed on the right eyes of Dutch belted rabbits, whereas the left eyes served as controls. The laser power settings were 250, 500, 750, 1000, 1500, and 2000 mW, 10 seconds per sweep, 100 seconds in total. IOP, outflow facility, and uveoscleral outflow tract imaging, using a fluorescent tracer, were examined at one week after MP-CPC. Changes of morphology and protein expressions in the outflow tissues, conjunctiva, and sclera were also evaluated.ResultsSignificant reductions in IOP after MP-CPC were observed at 500 to 1000 mW (P = 0.036 and P = 0.014, respectively). The pre-MP-CPC IOP was 11.35 ± 0.41 mm Hg. At one week after surgery, the respective IOP values in the eyes treated at 500 mW and 1000 mW were 9.45 ± 0.49 mm Hg and 7.4 ± 0.27 mm Hg, respectively. Severe ciliary body damage was observed at 1500 to 2000 mW. MMP1–3 and fibronectin expression levels in the outflow tract and ciliary body were upregulated after MP-CPC. The α-smooth muscle actin (α-SMA) was upregulated at higher power levels. MP-CPC significantly increased uveoscleral outflow, whereas the outflow facility did not change. The α-SMA, collagen, and fibronectin were significantly upregulated in the subconjunctiva and sclera.ConclusionsReactive fibrotic responses were observed in the outflow tract, conjunctiva, and sclera after MP-CPC. A potential mechanism of IOP reduction by MP-CPC in pigmented rabbit eyes may involve increased uveoscleral outflow related to MMP upregulation.

Cataract Formation by Near-infrared Radiation in Rabbits.

Surveys and epidemiological studies have shown an increased prevalence of cataracts in workers in the glass and steel industries. These cataracts are associated with exposure to intense infrared radiation (IR) emitted from heated materials and industrial furnaces. Thermal model calculations predicted that near and far IR would cause cataract with different mechanisms. The present study investigated cataract formation by near IR. Eyes of pigmented rabbits were exposed to IR at a wavelength of 808nm. Morphological changes in the anterior segment of the eye were assessed by slit-lamp microscopy, and temperature distributions in the anterior chamber of the eye were observed during IR exposure using microencapsulated thermochromic liquid crystals. Cortical cataract appeared below the exposed area of the iris in eyes that had been exposed for 6min to an irradiance of 1.27Wcm-2 or higher. The monitored temperature in the anterior chamber began to increase in the region adjacent to the exposed area of the iris with the onset of IR exposure. These results demonstrate that 808-nm IR is absorbed and converted to heat within the iris, which is then conducted to the lens and produce a cataract, as Goldmann theory states.

Clinical Course of High-Frequency Millimeter-Wave (162\xa0GHz) Induced Ocular Injuries and Investigation of Damage Thresholds

The objective was to investigate the clinical course of ocular damage and the healing process in eyes exposed to 162 GHz millimeter wave (MMW). As a 162-GHz electromagnetic wave source, a gyrotron FU CW GV was used. An ocular damaged rabbit model with good reproducibility for 162 GHz MMW exposure was developed, and damage occurrence threshold values were obtained. The right eyes of pigmented rabbits were exposed to 162 GHz from a spot-focus-type lens antenna, and the non-exposed contralateral eyes were used as control eyes. Slit-lamp examination 1 day after MMW exposure revealed a round area of opacity, characterized by fluorescein staining indicating damaged epithelial cells in the central pupillary zone. Corneal edema, indicative of corneal stromal damage, peaked 2–3 days after exposure, with thickness gradually subsiding to normal by 9 days after exposure. Power densities of 162 GHz MMW causing ocular damage with probabilities of 10, 50, and 90% obtained by probit analysis were 173, 252, and 368 mW/cm2, respectively.

Ultralow energy photoacoustic microscopy for ocular imaging in vivo.

.Significance: The development of ultralow energy photoacoustic microscopy (PAM) on the clinically relevant pigmented rabbit eye model paves a road toward translation of the emerging PAM technology in ophthalmology clinics.Aim: Since the eye is particularly vulnerable to laser damage, we aim to develop an ultralow energy PAM system to significantly improve the laser safety of PAM by increasing the sensitivity of the system and reducing the incident laser energy for imaging.Approach: A multichannel data acquisition circuit with two-stage signal amplification was specially designed, which, in combination with the application of 3 by 3 median filter in the spatial domain, significantly improved the signal-to-noise ratio of the PAM system. The safety of this system was validated by histopathology, fluorescein angiography, and fundus photography.Results: Experiments performed on pigmented rabbits demonstrated that, when using this ultralow energy PAM system, satisfactory image quality can be achieved in the eye with an incident laser fluence that is only 1% of the American National Standards Institute safety limit. Fundus photography, fluorescein angiography, and histopathology were performed after the imaging procedure, and no retinal or ocular damage was observed.Conclusions: The proposed ultralow energy PAM system has excellent safety and holds potential to be developed into a clinical tool for ocular imaging.

Experimental model to evaluate the benefits of lutein to prevent retinal phototoxicity during pars plana vitrectomy surgery using xenon source light illumination in rabbits

BackgroundTo evaluate the benefits of lutein in preventing retinal phototoxicity generated by xenon light sources during vitreoretinal surgery.MethodsA prospective cross-sectional study in pigmented rabbit eyes exposed to different vitreoretinal surgery lighting simulations. Twenty Dutch-belted rabbits were divided into two groups exposed to two different xenon wavelength light sources filters (420 nm and 435 nm). In addition, two subgroups were administered with daily supplemental of 10 mg of Lutein systemically. Electroretinography (ERG), optical coherence tomography (OCT) and fluorescein angiography (FA) were performed before and after surgery to quantify the retinal damage.ResultsAll animals submitted to the experiment presented some degree of phototoxicity independent of wavelength light filter used. Retinal damage was evident as the FA presented areas of hyperfluorescence, and the OCT depicted increased reflective areas of the inner and outer retinal layers, and RPE. ERG showed a diffuse reduction of the a and b waves amplitudes in all animals.ConclusionUse of systemic administration of lutein showed no benefit to avoiding retinal phototoxicity generate to xenon light source using filters of 435 nm and 420 nm when comparing to the control group.

Ocular Response to Millimeter Wave Exposure Under Different Levels of Humidity

It is known that millimeter waves (MMW) are absorbed by surface tissue such as skin and the cornea. We previously demonstrated that MMW damages the eye by heat accumulation and transfer. To examine the influence of humidity on such damage, we investigated the difference in MMW-induced ocular tissue temperature increase under high (70%) and low (30%) relative humidity. Eyes of pigmented rabbits (Dutch, 11–15-week old) were exposed unilaterally to 40-GHz 200 mW/cm2 MMW for 5 or 30 min at the center of the pupillary area with a spot-focus type lens antenna. Infrared thermography was used to measure corneal surface temperature during exposure. Temperature of corneal stroma and lens nucleus were measured using a fluoroptic thermometer during 0–30-min exposure. To visualize the dynamic change of temperature and its distribution in the anterior chamber, saline containing 0.2% microencapsulated thermochromic liquid crystal (MTLC) was injected into the eye anterior chamber. All three temperature measurements were much higher under high than low humidity at 24 °C room temperature and MTLC results showed the same trend during MMW exposure. These findings indicate that humidity affects MMW-induced ocular temperature elevation. We showed that low humidity during MMW exposure decreased heat accumulation and transfer, whereas high humidity increased the thermal effect. The present data demonstrated that controlling the environmental humidity might have an impact on ocular damage in eyes exposed to MMW.

Patching retinal breaks with polyethylene glycol-based synthetic hydrogel sealant for retinal detachment in rabbits

The purpose of this study was to evaluate absorbable polyethylene glycol (PEG)-based synthetic hydrogel as a sealant for retinal breaks in rhegmatogenous retinal detachment (RD). A three-port, 25-gauge vitrectomy was performed on nine Dutch pigmented rabbit eyes. Subsequently, RD was induced by creating a retinal break. The retina was then reattached by fluid-air exchange. In six of nine eyes (RD-PEG group), PEG sealant was applied to completely cover the retinal breaks, and then photopolymerized with light; thereafter, intravitreous air was replaced with balanced salt solution (BSS). In the remaining three eyes (RD group), PEG sealant was not applied, but the intravitreous air was replaced with BSS. Ophthalmological examinations and intraocular pressure measurements were conducted preoperatively, and at 1 and 7 days, and 1, 3, and 6 months postoperatively. Histological examinations of the eyes were performed after 6 postoperative months. At surgery, retinal reattachment with PEG sealant was achieved in all eyes in the RD-PEG group. Fundoscopic and optical coherence tomographic examinations revealed that the retina remained attached in all the eyes of the RD-PEG group throughout the 6-month observation period. Histological examination revealed no signs of damage in the retinal layers at the edges of the retinal breaks that were in contact with the sealant. In the RD group, the retinas detached in all eyes within 7 days postoperatively. The PEG sealant closed the retinal breaks and maintained retinal reattachment. Intraocular tamponade was not necessary.

Ocular Effects of Exposure to 40, 75, and 95\xa0GHz Millimeter Waves

The objective of this study was to develop a model of ocular damage induced by 40, 75, and 95 GHz continuous millimeter waves (MMW), thereby allowing assessment of the clinical course of ocular damage resulting from exposure to thermal damage-inducing MMW. This study also examined the dependence of ocular damage on incident power density. Pigmented rabbit eyes were exposed to 40, 75, and 95 GHz MMW from a spot-focus-type lens antenna. Slight ocular damage was observed 10 min after MMW exposure, including reduced cornea thickness and reduced transparency. Diffuse fluorescein staining around the pupillary area indicated corneal epithelial injury. Slit-lamp examination 1 day after MMW exposure revealed a round area of opacity, accompanied by fluorescence staining, in the central pupillary zone. Corneal edema, indicative of corneal stromal damage, peaked 1 day after MMW exposure, with thickness gradually subsiding to normal. Three days after exposure, ocular conditions had almost normalized, though corneal thickness was slightly greater than that before exposure. The 50% probability of ocular damage (DD50) was in the order 40 > 95 ≈ 75 GHz at the same incident power densities.

The relationship between retinal damage and current intensity in a pre-clinical suprachoroidal-transretinal stimulation model using a laser-formed microporous electrode

Objective. Suprachoroidal-transretinal stimulation (STS) is a stimulation method for retinal prostheses. For STS-type retinal prostheses, we developed a new type of stimulating electrode called a femtosecond laser-induced porous electrode (FLiP electrode). To verify the safety of the FLiP electrode for STS, we investigated the characteristics of STS-induced retinal injury. Approach. Sixteen eyes of pigmented rabbits were studied in this in vivo study. For each examined eye, we implanted a single-channel FLiP electrode (diameter, 0.5 mm; height, 0.3 mm; geometric surface area, 0.43 mm2) in a scleral pocket created at the posterior pole of the eye. A return electrode (diameter, 0.5 mm; length, 3 mm) was inserted into the vitreous cavity. The eyes were divided into five groups, and each group was stimulated with a different current intensity. The stimulus intensities and the number of eyes in each group were as follows: 1.0 mA (n = 2), 1.5 mA (n = 3), 2.0 mA (n = 3), 2.5 mA (n = 4), and 3.0 mA (n = 2). Continuous biphasic pulses (0.5 ms/phase) were applied under general anesthesia at a frequency of 20 Hz for 48 h. Fundus photography, fluorescein angiography (FA), and optical coherence tomography were performed before and after applying the electrical stimulation to evaluate the retinal injury. Main results. The 1.0 mA and 1.5 mA groups showed little or no retinal damage. Fluorescent dye leakage in FA and punctate pigmentation in the fundus were observed around the stimulation site with stimulation of 2.0 mA (1/3), 2.5 mA (1/4), and 3.0 mA (2/2). Significance. Our findings indicate that the threshold current for inducing retinal damage is greater than that for eliciting electrical phosphenes (<1 mA) with STS observed in human trials. Therefore, STS by the FLiP electrode is a safe and feasible stimulation method for retinal prostheses as long as it is used with these pulse parameters.

Polyethylene Glycol-Based Synthetic Hydrogel Sealant for Closing Vitrectomy Wounds: An In Vivo and Histological Study.

PurposeWe conducted an in vivo study using Dutch pigmented rabbit eyes to test the usefulness of polyethylene glycol (PEG) sealant for the closure of sutureless sclerotomies in microincisional vitrectomy surgery (MIVS).MethodsThree-port, 23-gauge vitrectomy was performed on rabbit eyes. After air leakage was confirmed by the application of 0.625% povidone–iodine at the sclerotomy site, PEG sealant was subconjunctivally injected using a 27-gauge needle through conjunctival incisions to cover the sclerotomy wounds, following which it was polymerized by the application of xenon light for 60 seconds. Ophthalmological examinations and intraocular pressure measurements were conducted the day before and 1, 3, 5, and 7 days after surgery. The eyes were enucleated for histological evaluation 7 days after surgery.ResultsPEG sealant was rapidly polymerized by the application of xenon light after subconjunctival injection, and it firmly sealed the sclerotomies without air leakage, as confirmed by povidone–iodine dropping, in all cases. Conjunctival and scleral wounds closed with PEG sealant were successfully attached and remained intact till the end of the follow-up period. There was no sign of postoperative hypotony or infection in any eye, and no adverse effects of PEG sealant were found. In histological examination, linear scar formation and eosinophilic staining of collagen fibers were observed at the sclerotomy sites, while the sclerotomy tunnels appeared tightly closed.ConclusionsPEG sealant can be useful for the closure of sutureless 23-gauge vitrectomy incisions in rabbits.Translational RelevanceThe PEG sealant may become an effective option for closing vitrectomy incisions including pediatric cases.

Laser speckle and hydrogen gas clearance measurements of optic nerve circulation in albino and pigmented rabbits with or without optic disc atrophy.

The purpose of this study was to evaluate the correlation between laser speckle flowgraphy measurements of mean blur rate (MBR) and hydrogen gas clearance measurements of capillary blood flow (CBF) in the optic nerve head (ONH) of albino and pigmented rabbits, with or without chronic ischemia-induced ONH atrophy. The ONH MBR and ONH CBF were measured at baseline, 30 and 60 minutes after the intravenous administration of endothelin-1 (ET-1) (10(-10) mol/kg) in six albino and six pigmented rabbit eyes. The ONH MBR and ONH CBF were also measured in nine pigmented rabbit eyes that underwent the intravitreal administration of ET-1 (20 pmol) twice per week for 4 weeks to provoke chronic ischemia-induced ONH atrophy. In the group that received intravenous ET-1, average measurements of ONH MBR and ONH CBF at all time points were correlated in both the albino (r = 0.88, P < 0.001, n = 18) and pigmented rabbits (r = 0.85, P < 0.001, n = 18), with no intrarabbit correlations (P = 0.524). The ONH MBR and ONH CBF were also correlated in the model of chronic ischemia-induced ONH atrophy (r = 0.78, P = 0.013, n = 9). Pooled ONH MBR and ONH CBF measurements in both the intravenous and intravitreal groups were also highly correlated (r = 0.87, P < 0.001, n = 45), with no significant intergroup differences in the relationship between ONH MBR and ONH CBF (P = 0.138). Regardless of the presence of fundus pigmentation or ONH atrophy, ONH MBR and ONH CBF were highly correlated, suggesting that MBR in the ONH tissue is usable for interindividual and intergroup comparisons.

Effects of Argon Laser Iridotomy on the Corneal Endothelium of Pigmented Rabbit Eyes

PurposeIn Asian countries, laser iridotomy for the treatment of angle-closure glaucoma is a common cause of bullous keratopathy, which may be associated with a shallow anterior chamber and dark iris pigmentation in Asians. Several cases of corneal decompensation after argon laser iridotomy have been reported. In the present study, we evaluated the harmful effects of argon laser iridotomy on the corneal endothelium.MethodsArgon laser iridotomy was performed on the right eyes of pigmented rabbits. Changes in corneal thickness and endothelial cell density after laser iridotomy were evaluated. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed for assessment of corneal endothelial cell apoptosis. Combined staining with alizarin red and trypan blue, as well as a live/dead cell assay, were performed for evaluation of damage to the corneal endothelium induced by laser iridotomy.ResultsCorneal thickness did not change immediately after laser iridotomy; however, a significant increase was observed 24 hours after iridotomy (p = 0.001). The endothelial cell density of laser-treated eyes four days after laser iridotomy was significantly decreased compared with control eyes (p < 0.001). TUNEL staining showed many TUNEL-positive cells in the corneal endothelium and corneal stroma. No endothelial trypan blue-stained cell nuclei were observed after laser iridotomy; however, several large endothelial cells with damaged membrane integrity were observed. The live/dead cell assay clearly showed a large number of dead cells stained red in several areas throughout the entire corneal button 24 hours after iridotomy.ConclusionsArgon laser iridotomy induces corneal endothelial cell apoptosis in pigmented rabbit eyes, resulting in decreased endothelial cell density.

Retinal injury thresholds for 532, 578, and 630 nm lasers in connection to photodynamic therapy for choroidal neovascularization

The purpose of this study was to explore the retinal injury thresholds in rabbits and evaluate the influence of retinal pigmentation on threshold irradiance at laser wavelengths of 532, 578, and 630 nm which might be involved in hypocrellin B (HB) and hematoporphyrin monomethyl ether (HMME) photodynamic therapy (PDT) for choroidal neovascularization (CNV). The eyes of pigmented and non-pigmented rabbits were exposed to 532, 578, and 630 nm lasers coupled to a slit lamp biological microscope. The exposure duration was 100 seconds and the retinal spot size was 2 mm throughout the experiment. The minimum visible lesions were detected by funduscopy at 1 and 24 hours post exposure. Bliss probit analysis was performed to determine the ED50 thresholds, fiducial limits and probit slope. In pigmented rabbits, the 24-hour retinal threshold irradiances at 532, 578, and 630 nm were 1,003, 1,475, and 1,720 mW/cm(2) , respectively. In non-pigmented rabbits, the 24-hour threshold irradiances were 1,657, 1,865, and 15,360 mW/cm(2) , respectively. The ED50 for 24-hour observation differed very little from the ED50 for 1-hour observation. The non-pigmented rabbits required a ninefold increase in threshold irradiance at 630 nm comparing to the pigmented rabbits. This study will contribute to the knowledge base for the limits of laser irradiance in application of HB or HMME PDT for CNV.

Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes

PurposeTo compare the aqueous humor (AH) and iris-ciliary body (ICB) concentration of bimatoprost in rabbit eyes treated with ISV-215 (0.03% bimatoprost formulated in DuraSite) with the marketed product bimatoprost 0.03% ophthalmic solution.MethodsThe left eye of rabbits received a single topical instillation of either ISV-215 (n = 32 eyes) or bimatoprost 0.03% (n = 32 eyes). At predetermined time points, levels of bimatoprost and bimatoprost acid in the AH and the ICB were quantified by HPLC-MS/MS.ResultsBoth bimatoprost and bimatoprost acid were detected in the AH and the ICB within 15 minutes of dosing. Bimatoprost acid concentrations in both compartments were markedly higher than bimatoprost. There was a statistically significant (P < 0.01) increase in the concentration of the prodrug in the AH and its acid form in the ICB in animals treated with ISV-215 compared to bimatoprost 0.03%. In the ISV-215-treated rabbit eyes, the highest concentrations of bimatoprost and bimatoprost acid were in the ICB and AH, respectively, while in the bimatoprost 0.03%-treated eyes, no differences in the drug content of the selected ocular tissues were observed.ConclusionsBimatoprost 0.03% formulated in DuraSite has superior ocular distribution and area under the curve compared to bimatoprost 0.03% in rabbit eyes. This improvement in the pharmacokinetic parameters of ISV-215 may provide us with a better platform to optimize a bimatoprost formulation that offers the same degree of efficacy in lowering intraocular pressure and improved therapeutic index in glaucomatous patients by lessening the ocular side effects associated with long-term use of topical prostaglandin F2α analogs.

Evaluation of extended release brimonidine intravitreal device in normotensive rabbit eyes

To evaluate the safety profile of a brimonidine extended release intravitreal implant, in normotensive rabbit eyes. Devices were made from hollow poly-l-lactic acid (PLA) tubes and contained hundred micrograms of brimonidine pamoate. Device was injected intravitreally in one eye of 12 New Zealand pigmented rabbits, whereas other eye was injected with a sham implant in masked fashion. Ocular examination was conducted at baseline and months 1, 3 and 6 including dilated fundus examination and electro-retinogram (ERG). Four rabbits were sacrificed at each time-point for retinal histology. ERG data were compared between groups and time-points using anova. No complications were reported from either eye of any rabbits over a 6-month period. Photopic A wave was reduced in the control eye at 1 month compared with baseline (p < 0.01). There was no significant difference in other ERG parameters between the groups at different time-points. Gross retinal histology was normal at all time-points. Extended release intravitreal brimonidine device was found to be safe and in normotensive rabbit eyes.

Novel ophthalmic timolol meleate liposomal-hydrogel and its improved local glaucomatous therapeutic effect in vivo

To overcome the limitations of common eye drops, the study developed a novel timolol mealate (TM) liposomal-hydrogel to enhance drug permeability and prolong residence time in the precorneal region, which achieved more effective local glaucomatous therapeutic effect. Firstly, TM liposome was prepared by an ammonium sulfate gradient-pH regulation method, which its entrapment efficiency reached up to 94% and its averaged particle size is 187 nm with narrow distribution. The corneal permeability through isolated rabbit cornea was measured by modified Franz-type diffusion cells. The results of trans-corneal penetration exhibited that the apparent permeability coefficients (Papp) and the flow rates of steady state (Jss) of TM liposome was 1.50-fold higher than that of the commercialized eye drop, while TM liposome with 0.02% transcutol P was 2.19 times. In order to increase the retention time and improve the stability of liposome, we further developed a TM liposomal-hydrogel formulation by adding 1.0% HPMC K4M in TM liposome. The results showed an stability during a 120 days storage period than TM liposome. Precorneal retention study in vivo indicated that the optimal liposomal-hydrogel formulation had improved bioavailability and its retention time on rabbit corneal surface were significantly longer than that of pure liposomes or eye-drops. No obvious irritations to rabbit eyes were observed by histopathology microscopy after 7 days exposure.. Comparing to the eye drops, the TM liposomal-gel displayed prolonged therapeutic effect in cornea and greatly lowered the intraocular pressure IOP on the eyes of normal and glaucomatous pigmented rabbits.

A possible mechanism for transpupillary thermotherapy: nitric-oxide-related cellular damage.

To determine the oxidative stress markers on rabbit vitreous following transpupillary thermotherapy (TTT) application. The pigmented rabbit eyes were divided into 3 groups, each containing 6 eyes. Group 1 was used as a control group. Twelve eyes underwent TTT with a power of 250 mW (group 2) and 800 mW (group 3), with a diameter of 3000 microm and duration of 60 s; 24 h after laser application, vitreous samples were collected. Nitric oxide (NO) and malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities were determined in all groups. NO levels were statistically significantly higher in all groups when compared with the control group (p < 0.05). MDA levels were higher and SOD activities were lower in all groups when compared with the control group, but the differences were not significant statistically (p > 0.05). Our results support the hypothesis that TTT application induces NO synthesis, which may lead to occlusion at choroidal neovessels. Because of the nonsignificantly increased levels of MDA and decrease of SOD activities there maybe only a weak relation between lipid peroxidation induced by free oxygen radicals and TTT-induced vascular damage.

Anti-inflammatory effect of the alpha-melanocyte stimulating hormonein animal eyes undergoing extracapsular lens extraction

In this study anti-inflammatory effects of the alpha-melanocyte stimulating hormone (alpha-MSH) on ocular inflammation caused by extracapsular lens extraction (ECLE) have been investigated and the potential mechanism of an anti-inflammatory effect is discussed. Pigmented rabbit eyes after ECLE were treated locally with alpha-MSH, dexamethasone, diclofenac, or saline 4 times a day (q.i.d.) for 4 weeks. The inhibitory effect of alpha-MSH on infiltrating cells in the aqueous humor (AqH) was almost twice as good as that of dexamethasone or diclofenac for 3 days, 1 week, and 2 weeks after the operation. The eyes of Sprague-Dawley rats were treated with an intravenous injection of alpha-MSH or saline immediately after ECLE. Six hours postoperatively, the iris/ciliary body exhibited increased expression of TNF-alpha and IL-6 mRNAs, which were significantly decreased after alpha-MSH treatment. The number of activated NF-kappa B (NFkappaB)-positive cells in the iris/ciliary body was also significantly reduced by the alpha-MSH treatment. These results suggested that alpha-MSH could effectively reduce ocular inflammation after ECLE, and the potential mechanism for this is by down-regulating the expression of proinflammatory cytokines and inhibiting the NFkappaB-dependent signaling pathway.

Ocular Distribution of Difluprednate Ophthalmic Emulsion 0.05% in Rabbits

To evaluate ocular distribution and excretion of tritium-labeled difluprednate ((3)H-DFBA) ophthalmic emulsion 0.05% after a single or repeated instillation to pigmented rabbit eyes. (3)H-DFBA ophthalmic emulsion 0.05% was instilled in the right eyes of pigmented rabbits, in either a single or repeated quater in die (QID) for 3 days or 7 days) dose of 25 μg/50 μL. The radioactivity in right and left ocular tissues, urine, blood, plasma, and feces were measured with a liquid scintillation counter. Additionally, the distribution of radioactivity around ocular tissues was investigated with autoradiography. After a single instillation, the highest maximum radioactive concentrations were found in the cornea (2,081 ng eq./g), followed by the iris/ciliary body (926 ng eq./g), conjunctiva (330 ng eq./g), anterior retina/choroid (273 ng eq./g), sclera (222 ng eq./g), and aqueous humor (144 ng eq./mL) of treated eyes. The maximum radioactivity concentration of the posterior retina/choroid was 59 ng eq./g, and difluprednate delivered as a topical ophthalmic emulsion reached the back of the eye. However, radioactivity in untreated eyes was very low. Total radioactivity excreted in urine and feces 168 h after a single instillation was 99.5% of the total dose. Radioactivity concentration levels measured 24 h after 28 instillations were no more than twice those measured 24 h after 12 instillations. Radioactive concentrations in ocular and periocular tissues were highest at 0.5 or 1 h after a single instillation, and were mostly eliminated from these tissues by the end of the study. Radioactivity was barely detectable in the blood, with very little accumulation even after multiple doses. After instillation of (3)H-DFBA ophthalmic emulsion 0.05% in rabbit eyes, radioactivity was distributed at the anterior segment and cleared rapidly. Some radioactivity was detected in the posterior retina/choroid, suggesting that difluprednate and its metabolites reach these tissues. These results suggest that difluprednate delivered as a topical ophthalmic emulsion reached the anterior and posterior segments of the eye quickly and may be a potential treatment for ocular inflammation in these areas.