Prediction of Ocular Irritancy of 26 Chemicals and 26 Cosmetic Products with Isolated Rabbit Eye (IRE) Test

Objective This study aims to establish and evaluate the methodology of isolated rabbit eye （IRE） test. Methods IRE test was performed according to modifications of the in vitro toxicology （INVITTOX） Protocol No.85： Rabbit enucleated eye test by European Centre for the Validation of Alternative Methods （ECVAM）, and then 26 chemicals and 26 cosmetic products were tested in both in vitro IRE and in vivo Draize tests. A statistical analysis was conducted to determine the relevance of the IRE test to the data generated in the Draize test. Results IRE test was established successfully in our laboratory. It was shown that ranking correlation and class concordance were fairly well between the IRE test and the Draize test for 26 reference chemicals （Fisher＇s Exact Test X2=51.314, P〈0.001; McNemar P=0.261; Gamma=0.960, P〈0.001; Kappa=0.843, P〈0.001） and 26 cosmetic products （Fisher＇s Exact Test X^2=15.522, P〈0.O01; McNemar P=0.311; Gamma=0.967, P〈0.001; Kappa=0.611, P〈0.O01）. Conclusion IRE test was established successfully for in vitro testing of eye irritation as an alternative to Draize test.

Application of sustained delivery microsphere of cyclosporine A for preventing posterior capsular opacification in rabbits

AIM:To explore the inhibitory effect of a sustained cyclosporin A (CsA) delivery microsphere (CsA-MS) on posterior capsular opacification (PCO) in rabbit eyes after cataract extraction. ·METHODS:Twenty New Zealand white rabbits accepted cataract extraction plus intraocular lens implantation and their left eyes were intraoperatively injected CsA-MS prepared using polymer polylactioglycolic acid (PLGA) as a carrier and their right eyes were injected with empty MS. The changes in cornea, anterior chamber reaction, intraocular pressure, PCO and CsA concentration in aqueous humor were examined postoperatively and all the eyes were enucleated 3 months after surgery for histopathological and morphological examination with light microscopy and electron microscopy. · RESULTS:Conjunctival hyperemia, corneal edema, intraocular pressure and anterior chamber response of experimental and control eyes were similar, while PCO in CsA MS injected eyes was greatly improved compared with that in control eyes. Posterior capsules in CsA-MS injected eyes were smooth and lens epithelial cells (LEC) did not proliferate significantly (P 】0.05), while LEC in posterior capsule of control eyes had different degrees of proliferation and cortical regeneration. LEC in CsA-MS injected eyes were not functionally active and underwent apoptosis, whereas LEC in control eyes were functionally active (F-test, P =0.025). In addition, the cornealultrastructure showed no differences between CsA-MS and MS injected eyes. CONCLUSION:CsA-MS has high bioavailability in rabbit eyes and could inhibit postoperative PCO occurrence and development during the study period, suggesting that CsA-MS may be a promising, effective and safe administration route to prevent PCO in clinic.

Ocular penetration of topically applied 1% tigecycline in a rabbit model

AIM：To evaluate ocular penetration of topically applied 1% tigecycline.METHODS：Forty-two New Zealand White rabbits were divided into 3 groups. A 50 μL drop of 1% tigecycline was administered in group 1. In groups 2 and 3, the drop was administered every 15 min for 60min（keratitis protocol）. Aqueous humor samples in groups 1 and 2 were collected under general anesthesia at 15, 30, 45, 60, 120, and 180 min after the last drop. All animals in group 3 were euthanatized. Cornea, vitreous and blood samples were collected 60 and 120 min after the last drop. Tigecycline concentrations were measured using high performance liquid chromatography-mass spectrometry（LC-MS/MS）.RESULTS：The peak aqueous humor tigecycline concentration [mean 0.73±0.14 mg/L（SD） and 2.41±0.14 mg/L, respectively] occurred 45 min after topical drug application in groups 1 and 2. Group 3 mean values in the cornea, and vitreous, were 3.27±0.50 μg/g, and 0.17±0.10 mg/L at 60 min and 3.17±0.77 μg/g and 0.20±0.07 mg/L at 120 min, respectively. Tigecycline serum concentrations were negligible.CONCLUSION：Tigecycline levels in the aqueous humor in groups 1 and 2, and in the cornea in group 3 exceeded the minimum inhibitory concentrations of most grampositive organisms that cause bacterial keratitis and endophthalmitis.