Total glucosides of paeony (TGP) are active components extracted from the roots of Paeonia lactiflora Pall. In this study, we investigated the role and mechanisms of TGP in experimental autoimmune uveitis (EAU) model of mice. The C57BL/6 mice were randomly divided into three groups: sham group, EAU-control group, and EAU-TGP group. Clinical score of images of the eye fundus were taken on 7, 14, 21, and 28 days after induction of EAU. The concentrations of proinflammatory cytokines in intraocular fluid were measured at 14 days after EAU induction with the use of a multiplex assay system. Flow cytometry was used to analyze the frequency of CD4+, CD8+, interferon-gamma (IFN-γ), and CD4+/CD8+ ratio in spleen and lymph nodes. Western blotting was used to measure expressions of mitogen-activated protein kinase (MAPK) pathway-related proteins in retina. Clinical scores for uveitis were lower in TGP-treated EAU mice than those without TGP treatment. Importantly, the concentrations of cytokines induced by T-helper 1 (Th1) and T-helper 2 (Th2) cells in intraocular fluid were reduced in EAU mice treated with TGP. Furthermore, the frequency of CD4+, IFN-γ, and CD4+/CD8+ ratio was decreased and the frequency of CD8+ was increased in spleen and lymph nodes of mice treated with TGP. The anti-inflammatory effects of TGP were mediated by inhibiting the MAPK signaling pathways. Our results showed that TGP suppressed uveitis in mice via the inhibition of Th1 and Th2 cell function. Thus, TGP may be a promising therapeutic strategy for uveitis, as well as other ocular inflammatory diseases.

Background: The aim of this study was to compare the distribution characteristics and ocular pharmacokinetics of norvancomycin (NVCM) in ocular tissues of the anterior segment between continuous topical ocular instillation and hourly administration of eye drop in rabbits. Methods: Sixty rabbits were randomly divided into two groups: continuous topical ocular instillation drug delivery (CTOIDD) group and eye drop (control) group. In the CTOIDD group, NVCM solution (50 mg/mL) was perfused to the ocular surface using the CTOIDD system at 2 mL/ h up to 10 h and the same solution was administered at one drop (50 μL) per hour for 10 h in the control group. Animals (N=6 per time-point per group) were humanely killed at 2, 4, 6, 10, and 24 h to analyze their ocular tissues and plasma. The concentrations of NVCM in the conjunctiva, cornea, aqueous humour, iris, ciliary body and plasma were measured by HPLC with photodiode array detector. The pharmacokinetic parameters were calculated by Kinetica 5.1. Results: The highest concentrations of NVCM for the CTOIDD group and control group were 2105.45±919.89 μg/g and 97.18±43.14 μg/g in cornea, 3033.92±1061.95 μg/g and 806.99 ±563.02 μg/g in conjunctiva, 1570.19±402.87 μg/g and 46.93±23.46 μg/g in iris, 181.94 ±47.11 μg/g and 15.38±4.00 μg/g in ciliary body, 29.78±4.90 μg/mL and 3.20±1.48 μg/mL in aqueous humour, and 26.89±5.57 μg/mL and 1.90±1.87 μg/mL in plasma, respectively. The mean NVCM levels significantly increased at all time-points in cornea, iris, and ciliary body (p<0.05) in the CTOIDD group. The AUC 0-24 values in the CTOIDD group were 27,543.70 μg•h/g in cornea, 32,514.48 μg•h/g in conjunctiva, 8631.05 μg•h/g in iris, 2194.36 μg•h/g in ciliary body and 343.9 μg•h/mL in aqueous humour, which were higher than for the eye drop group in all tissues. Conclusion: Since continuous instillation of NVCM with CTOIDD could reach significantly higher concentrations and was sustained for a longer period compared with hourly administration of eye drop, CTOIDD administered NVCM could be a possible method to treat bacterial keratitis.

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To compare the safety of implantable Collamer lens (ICL) implantation with and without ophthalmic viscosurgical device (OVD). A total of 148 eyes underwent a conventional ICL implantation with OVD (OVD group), and 112 eyes underwent a modified ICL implantation without OVD (OVD-free group). The balanced salt solution was used to load ICL and maintain the anterior chamber in the OVD-free group. The surgical time, postoperative uncorrected distance visual acuity, intraocular pressure, endothelial cell density (ECD), and percentage of hexagonal cells were compared between the OVD and the OVD-free groups. No significant differences were detected in uncorrected distance visual acuity, intraocular pressure, ECD, and percentage of hexagonal cells at any time post-surgery between the 2 groups (P > .05). The mean ECD loss was 1.9% in the OVD-free group and 2.3% in the OVD group at 2 years post-surgery (P = .680). The surgical time was much shorter in the OVD-free group than that in the OVD group (P ≤ .001). None of the following occurred at any time during the 2-year follow-up period in both groups: cataract formation, macular degeneration, or any other vision-threatening complications. OVD-free ICL implantation presented satisfactory results for safety. Compared to OVD, the OVD-free technique had the advantages of decreased surgical time, increased efficiency, and reduced cost.

Purpose To explore the feasibility of cyclophosphamide (CP) via a sub-Tenon micro-perfusion system (SMS) in rabbits, and assess its therapeutic efficacy in severe ocular inflammation. Materials and Methods Distribution and pharmacokinetics of CP were evaluated in vivo, and the concentrations of CP in plasma, vitreous humor, and retina/choroid were quantitated by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) at different time points. After induction of severe experimental uveitis, rabbits were divided into three groups (n=8 in each): the SMS group, subconjunctival injection (SI) group, and control group. Clinical inflammatory score was assessed in rabbits. Electroretinography and histopathology were performed on post-treatment day 8. Statistical analyses were performed using Mann–Whitney and Kruskal–Wallis tests. P -value less than 0.05 was considered significant. Results The concentrations of CP in vitreous humor and retina/choroid in the SMS group were significantly higher than that of the SI group at 3, 6, 10, and 24 hours ( P <0.01), while plasmatic CP concentrations were comparable at all time points in the SMS group and SI group ( P >0.05). The SMS group showed significantly less inflammation compared to the control group and SI group. Furthermore, the restoration of retinal structure and function were more obvious in the SMS group compared with conventional SI application. Conclusion Sub-Tenon micro-perfusion of CP exhibited satisfied therapeutic efficacy in rabbits with severe ocular inflammation and may provide a promising alternative for controlling ocular inflammatory disease and immune-mediated ocular diseases.