Presumed congenital nictitating membrane dysplasia in a Japanese white rabbit.

OBJECTIVE: The present report characterises a spontaneous nictitating membrane abnormality in a Japanese white rabbit. ANIMAL STUDIED: The animal was a male Japanese white rabbit (Oryctolagus cuniculus, Kbs:JW, 10 weeks old at the time of purchase) that had not received any treatment. A morphological abnormality of the nictitating membrane in the animal's right eye was detected. PROCEDURES: Ophthalmological examinations, including slit-lamp biomicroscopy, corneal and conjunctival staining with fluorescein and lissamine green, fundoscopy, blinking rate measurement, Schirmer's tear test, and tonometry were performed. The animal was euthanised at 15 weeks of age, and histopathological examinations of the abnormal nictitating membrane, palpebral conjunctiva, eyelid and eyeball were performed. RESULTS: The tip of the nictitating membrane adhered to the palpebral conjunctiva of the medial canthus. The eye and periocular tissues showed no abnormalities in the ophthalmological examinations, except for the structure of the nictitating membrane. Histopathological examination revealed that the adhered site of the nictitating membrane and the palpebral conjunctiva consisted of dense fibrous connective tissue that was consecutive to the conjunctiva adjacent to the eyelid margin and lamina propria of the nictitating membrane. The fibrous connective tissue was covered with stratified squamous epithelium. CONCLUSION: Based on these results, we diagnosed this abnormal finding as congenital nictitating membrane dysplasia. This paper is the first case report describing a congenital structural abnormality of the nictitating membrane in a Japanese white rabbit.

Characteristics of corneal phospholipidosis induced by topical ocular application of chloroquine and amiodarone in rabbits.

Several cationic-amphiphilic drugs such as chloroquine and amiodarone are known to induce phospholipidosis in the cornea by systemic administration. However, the characteristics of ophthalmological and pathological changes when phospholipidosis-inducing drugs are topically applied have not been well studied. This study was conducted to investigate the characteristics of corneal changes caused by topical application of chloroquine and amiodarone to Japanese white rabbits. The changes were evaluated by ophthalmological, histopathological, and ultrastructural examinations. An in vivo confocal microscopy was also applied to the chloroquine-treated corneas. In both chloroquine- and amiodarone-treated corneas, diffuse cloudiness was observed by slit-lamp biomicroscopy, and its transparency increased with duration of dosing. Confocal microscopy showed punctate dots in the corneal epithelium. Histopathologically, cytoplasmic vacuolation was found in the corneal epithelium and keratocytes in both chloroquine- and amiodarone-treated eyes. Furthermore, foamy cytoplasm of the corneal endothelium was observed in the chloroquine-treated eyes. Ultrastructural examination showed multi-lamellar inclusion bodies or membrane-like debris in the lysosome-like vacuoles in the cytoplasm of corneal cells, which is a characteristic of the lesions of phospholipidosis. These changes disappeared after a withdrawal period. Continuous dosing of chloroquine resulted in corneal erosion and focal corneal opacity as shown by gross observation and slit-lamp biomicroscopy. Confocal microscopy could detect the corneal changes prior to the appearance of these ophthalmological changes. The present study showed that phospholipidosis caused by ocular administration of chloroquine and amiodarone first induces reversible diffuse corneal cloudiness. Confocal microscopy is a useful method for monitoring induction of corneal phospholipidosis.

Bepotastine besilate, a highly selective histamine H(1) receptor antagonist, suppresses vascular hyperpermeability and eosinophil recruitment in in vitro and in vivo experimental allergic conjunctivitis models.

To elucidate the ocular pharmacological properties of bepotastine besilate, a selective histamine H(1) receptor antagonist, when compared with other histamine H(1) receptor antagonists, using guinea pig allergic conjunctivitis models and in vitro models of eosinophil recruitment and mast cell membrane stabilization. Conjunctival vascular hyperpermeability was studied in guinea pigs passively sensitized with anti-ovalbumin antiserum or following subconjunctival injection of histamine. Modulation of eosinophil recruitment was evaluated for both platelet-activating factor (PAF)-induced eosinophil infiltration in guinea pigs and leukotriene B(4)-induced in vitro chemotaxis of guinea pig peritoneal eosinophils. Membrane-stabilizing effects of bepotastine also were studied with rat peritoneal mast cells stimulated with the ionophore A23187. Histamine H(1) receptor antagonists including bepotastine besilate were topically administered before ovalbumin, histamine or PAF challenges for in vivo experiments or were added directly to mast cell and eosinophil medium in vitro. Bepotastine besilate significantly inhibited conjunctival vascular hyperpermeability in a dose-dependent manner with maximal effect for bepotastine besilate 1.5%. In separate in vivo experiments, bepotastine besilate 1.0% was significantly more effective than levocabastine 0.025% in the passive sensitization model or olopatadine 0.1% in the histamine-induced hyperpermeability model. Bepotastine besilate 1.0% further suppressed PAF-induced eosinophil infiltration into conjunctival tissue more effectively than ketotifen 0.05%. Chemotaxis of guinea pig peritoneal eosinophils and histamine release from rat peritoneal mast cells in vitro were also inhibited by addition of bepotastine. Olopatadine had a weak effect as compared to that of bepotastine on eosinophil chemotaxis and no effect on mast cell histamine release in our study conditions. Bepotastine besilate was more potent than olopatadine, ketotifen, or levocabastine in reducing vascular hyperpermeability in various animal models of allergic conjunctivitis. Mast cell function and eosinophil chemotaxis were also inhibited in vitro with bepotastine, suggesting bepotastine acts as an inhibitor of allergic response through multiple mechanisms: histamine H(1) receptor antagonism, mast cell stabilization, and inhibition of eosinophil migration to ocular inflammatory sites.

Polylactic acid for visualizing the vitreous body during vitrectomy.

PURPOSE: To investigate the possibility of using polylactic acid (PLA) as a surgical adjuvant for visualizing the vitreous body during vitrectomy. METHODS: After a core vitrectomy, 1 mL of PLA suspension was injected into the rabbit vitreous in two groups: group A, 2.5% PLA (n = 5), and group B, 1% PLA (n = 9). Vehicle injection instead of PLA was used as a control (group C, n = 5). The clinical signs and electroretinogram (ERG) were evaluated for 28 days, and histologic findings were evaluated on day 28. Next, intraocular pressure (IOP) after intracameral injection of a PLA suspension was evaluated in the rabbits (n = 6). Last, the visualization of the vitreous body by PLA suspension was evaluated during vitrectomy in monkey eyes (n = 4). RESULTS: The white granules of PLA disappeared from the vitreous cavity in 10 eyes within 3 weeks; however, a small amount of PLA remained in four eyes for 4 weeks. Mild inflammation of the anterior chamber was observed in one eye in group B and 1 eye in group C. No cataract or retinal hemorrhage was found in any eyes. The amplitude of ERG on each time point did not differ between the groups. IOP remained within normal range except for the initial spike. Retinal structure was well preserved histologically. During vitrectomy in monkey eyes, the vitreous body was well visualized, and the posterior vitreous separation was performed easily and safely. CONCLUSIONS: PLA can be a new surgical adjuvant to visualize the vitreous body during vitrectomy.

Identification of C3a and N-truncated C3a as vascular permeability-enhancing factors from the exudate of chronic phase of carrageenan-induced inflammation in rats.

Two basic proteins enhancing vascular permeability have been purified from the exudate of the chronic phase of carrageenan-induced inflammation in rats. One major and one minor peak on reversed-phase HPLC showed molecular masses of 9.3 kDa and 7.6 kDa, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. NH2-terminal amino acid sequencing analysis of the purified proteins revealed that the major peak is identical to C3a, while the main sequence of the minor peak is identical to NH2-terminal 11 amino acids truncated C3a. In addition, plasmin was able to cleave C3a into the N-truncated C3a. Intradermal injection of both purified C3a and N-truncated C3a into rat skin enhanced vascular permeability, and the increased permeability was suppressed by the pretreatment with cyproheptadine. Our results suggest that the purified C3a and N-truncated C3a have the characteristics of anaphylatoxins and may contribute to exudation in the chronic phase of carrageenan-induced inflammation in rats.