Inflammation In Rabbit Eye Research Articles

Development of an Experimental Drug Eluting Suprachoroidal Microstent as Glaucoma Drainage Device.

A novel glaucoma drainage device (GDD) with local drug delivery (LDD) system was created and characterized for safety and effectiveness after implantation into the suprachoroidal space (SCS) of rabbit eyes. Thin films of two different polymers, Poly(3-hydroxybutyrate) (P(3HB)) and Poly(4-hydroxybutyrate) (P(4HB)), containing the drugs mitomycin C (MitC) or paclitaxel (PTX) were attached to silicone-tubes to create LDD devices. The release kinetics of these drugs were explored in vitro using high performance liquid chromatography (HPLC). Twenty-four New Zealand white rabbits, randomly divided into eight groups, were implanted with different kinds of microstents into SCS. The intraocular pressure (IOP) was monitored noninvasively. After 6 weeks, rabbits were sacrificed and enucleated eyes were used for anterior segment optical coherence tomography (OCT), micro magnetic resonance imaging (MRI), and histology. In vitro, faster drug release from both polymers was observed for MitC compared to PTX. Comparing polymers, the release from P(3HB) matrix was slower for both drugs. MRI and OCT showed all implants maintained a proper location. An effective IOP reduction was observed for up to 6 weeks in eyes with microstents combined with a drug-releasing LDD system. Overall, the surrounding tissue revealed mild-to-moderate inflammation. No pronounced fibrosis was observed in any of the groups. However, both drugs caused damage to the neighboring retina. The suprachoroidal microstent reduced IOP with mild inflammation in rabbit eyes. To avoid negative effects on the retina, it is necessary to identify novel drugs with less cytotoxicity. Future studies are needed to explore the fibrotic process over the long-term. The presented data serve as a proof of principle study for the concept of a suprachoroidal drug eluting microstent. Future device improvements will be focused on the design of LDD systems and the use of specific anti-inflammatory or antifibrotic agents with less cytotoxicity compared to MitC or PTX. Long-term animal studies using a reliable glaucoma model will be a further step towards clinical application and improvement of surgical glaucoma therapy.

Vorinostat: A Potent Agent to Prevent and Treat Laser-induced Corneal Haze

This study investigated the efficacy and safety of vorinostat, a deacetylase (HDAC) inhibitor, in the treatment of laser-induced corneal haze following photorefractive keratectomy (PRK) in rabbits in vivo and transforming growth factor beta 1 (TGFβ1) -induced corneal fibrosis in vitro. Corneal haze in rabbits was produced with -9.00 diopters (D) PRK. Fibrosis in cultured human and rabbit corneal fibroblasts was activated with TGFβ1. Vorinostat (25 μm) was topically applied once for 5 minutes on rabbit cornea immediately after PRK for in vivo studies. Vorinostat (0 to 25 μm) was given to human/rabbit corneal fibroblasts for 5 minutes or 48 hours for in vitro studies. Slit-lamp microscopy, TUNEL assay, and trypan blue were used to determined vorinostat toxicity, whereas real-time polymerase chain reaction, immunocytochemistry, and immunoblotting were used to measure its efficacy. Single 5-minute vorinostat (25 μm) topical application on the cornea following PRK significantly reduced corneal haze (P<.008) and fibrotic marker proteins (α-smooth muscle actin and f-actin; P<.001) without showing redness, swelling, or inflammation in rabbit eyes in vivo screened 4 weeks after PRK. Vorinostat reduced TGFβ1-induced fibrosis in human and rabbit corneas in vitro in a dose-dependent manner without altering cellular viability, phenotype, or proliferation. Vorinostat is non-cytotoxic and safe for the eye and has potential to prevent laser-induced corneal haze in patients undergoing PRK for high myopia.

Glycerogelatin-based ocular inserts of aceclofenac: Physicochemical, drug release studies and efficacy against prostaglandin E2-induced ocular inflammation

An attempt has been made in the present study to formulate soluble ocular inserts of aceclofenac to facilitate the bioavailability of the drug into the eye, as no eye drop solution could be formulated. Glycero-gelatin ocular inserts/films were prepared and physicochemical parameters and drug release profiles of glycerol-gelatin films of aceclofenac were compared with surface cross-linked films of similar compositions. Ocular irritation of the developed formulation was also checked by HET-CAM test and efficacy of the developed formulation against prostaglandin-induced ocular inflammation in rabbit eye was determined. The non-cross-linked films showed poor mechanical, physicochemical properties, and very little potential of sustaining drug release, however cross-linking the films enhanced tensile strength by 70%, but elasticity decreased by 95%. The cross-linked ocular inserts showed less swelling than non-cross-linked. Formulation AF8 (20% gelatin and 70% glycerin, treated by cross-linker for 1 h) demonstrated the longest drug release for 24 h. As per the kinetic models all films showed a constant drug release with Higuchi diffusion mechanism. Formulation was found to be practically non-irritant. The optimized formulation was tested and compared with eye drops of aceclofenac for anti-inflammatory activity in rabbits against PGE2-induced inflammation. In vivo studies with developed formulation indicated a significant inhibition of PGE2-induced PMN migration as compared to eye drops. In conclusion, ocular inserts of aceclofenac was found promising as it achieved sustained drug release and better pharmacodynamic activity.

Effect of Intracameral Triamcinolone to Control Inflammation in Rabbit Eyes

Purpose: To investigate the effect of intracameral triamcinolone on the control of inflammation with rupture of the posterior lens capsule during cataract surgery in rabbit eyes. Methods: Twenty rabbit eyes were subjected to experimentally induced rupture of the posterior lens capsule and prolapse of the vitreous body into the anterior chamber. After anterior vitrectomy with and without triamcinolone, aqueous flare was measured with a laser flare meter on days 1, 3, 7, 14 and 28. Results: Vitrectomized eyes with triamcinolone showed a less marked increase in postoperative aqueous flare intensity on days 14 and 28 than did those without triamcinolone (p

An Animal Model of Corneal Bacterial Infection Induced by Intra-Corneal Injection of Staphylococcus Epidermidis

Purpose: Pharmacokinetic studies of anti-bacterial agents for infectious eye diseases have usually been performed using non-infected rabbit eyes with few studies using infected animal eyes. Methods: In order to induce bacterial corneal inflammation in rabbit eyes, an intra-corneal injection of Staphylococcus epidermidis was done. The applied bacterial dose was 50 μL of 1 × 10 4 cfu/mL. Results: The characteristic corneal change was well-defined ulcer formation located in a limited area and relatively elevated. The area surrounding the infected part of the cornea was rather transparent. Using these infected eyes as models, the intraocular drug dynamics of 0.3% Ofloxacin were examined. The model was successfully induced in 78.6% of the rabbits. The drug concentration in the aqueous humor was 2 times higher in the infectious eyes than in the control eyes. Conclusion: The model might be useful for drug dynamic studies in infected eyes.

Experimental Uveitis Induced by Intravitreal or Intravenous Lipoteichoic Acid in Rabbits

Purpose: To investigate the role of lipoteichoic acid (LTA), one of the cell wall components in Gram-positive bacteria in uveitis. Methods: Intraocular inflammation in rabbit eyes was induced by intravitreal or intravenous injections of LTA from Staphylococcus aureus or Streptococcus sanguis. The inflammation was monitored progressively with the laser flare-cell photometer, and examined by periodic clinical observations. Histological examinations were performed 24 hours after administration, and aqueous protein concentrations and cell counts were also determined. Results: Intraocular inflammation appeared within 6–9 hours of LTA intravitreal injection, became maximal at about 24–48 hours postinjection, and lasted for nearly 6 days. Intraocular inflammation was also induced by intravenous injection of LTA at a higher dose. Inflammation reached a peak 4–5 hours after injection, and rapidly disappeared in 24 hours. No cellular response was observed in intravenous LTA-treated eyes. Conclusions: This study demonstrates that LTAs from Gram-positive bacteria have the biological activity to induce intraocular inflammation in rabbits by intravitreal or intravenous injection. Therefore, we suggest that LTA may play a role in the pathogenesis of uveitis as one of the etiological factors.

Annexin V—coated intraocular lenses

Purpose: To assess whether annexin V—coated poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) prevent postoperative inflammation in rabbit eyes.Setting: Department of Ophthalmology, Hopital Purpan, Toulouse, France.Methods: Thirteen IOLs coated with annexin V were implanted in 13 rabbit eyes; the contralateral eyes received uncoated IOLs. Postoperative fibrin was quantitated by daily slitlamp examination until the anterior chamber was completely clear. Results were analyzed using a Wilcoxon test. Ocular toxicity was evaluated by light and electron microscopy.Results: Eyes with the annexin V—coated IOLs had less severe inflammation on the first postoperative day, and the inflammation resolved more quickly than in eyes with uncoated IOLs (P < .05). No annexin V was released postoperatively, nor were there signs of ocular toxicity.Conclusion: Annexin V—coated lenses effectively reduced postoperative inflammation in rabbit eyes.

Endothelin-1 and intraocular inflammation in rabbit eyes

Endothelin-1 and intraocular inflammation in rabbit eyes