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. 2020 Aug 20:14:3407-3416.
doi: 10.2147/DDDT.S250541. eCollection 2020.

Efficacy of Sub-Tenon Micro-Perfusion of Cyclophosphamide in Rabbits with Severe Ocular Inflammation

Libei Zhao  1 , Manqiang Peng  1 , Wenxiang Lin  1 , Qian Tan  1 , Muhammad Ahmad Khan  1 , Ding Lin  1
Affiliations

Efficacy of Sub-Tenon Micro-Perfusion of Cyclophosphamide in Rabbits with Severe Ocular Inflammation

Libei Zhao et al. Drug Des Devel Ther. .

Abstract

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.

Keywords: cyclophosphamide; ocular inflammation; rabbit; sub-Tenon drug delivery; treatment.

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Conflict of interest statement

All authors declare no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Schematic of sub-Tenon micro-perfusion of CP in rabbit. CP was released via sub-Tenon micro-perfusion system consisting of a catheter, a micro-needle, and a micro-pump, then it permeated into the vitreous from the scleral surface.
Figure 2
Figure 2
CP distribution characteristics in plasma, vitreous humor, and retina/choroid via SMS and SI.
Figure 3
Figure 3
Images of the ocular appearance for the control group (A and D), SI group (B and E), and SMS group (C and F) on post-treatment days 3 and 7. The eyes in the control group had severe anterior chamber fibrin and vitreous opacity, whereas there were less inflammatory signs in the SI group and SMS group. The eyes at day 7 in the SMS group appeared normal. The arrow indicates the response of inflammation.
Figure 4
Figure 4
Clinical signs of inflammatory response in control group, SI group and SMS group. Mean anterior chamber fibrin scores (A) and mean vitreous opacity scores (B) were assessed on post-treatment days 3 and 7 (n=8). #P<0.05, ##P<0.01.
Figure 5
Figure 5
Representative histopathologic section images of the retina in the control group (A), SI group (B), SMS group (C), and normal rabbits (D) (20× magnification; Scale bar −50 µm). Sections of the retina were photographed on post-treatment day 8. Histological scores of the retina in the control group, SI group, and SMS group (E). *P<0.05, **P<0.01.
Figure 6
Figure 6
Scotopic ERG responses in the control group, SI group, SMS group, and normal rabbits. Mean b-wave amplitude in all groups were observed on post-treatment day 8 (n=8 eyes for each group). Error bars represent the SD, **P<0.01.
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References

    1. Dick AD, Tundia N, Sorg R, et al. Risk of ocular complications in patients with noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Ophthalmology. 2016;123(3):655–662. doi:10.1016/j.ophtha.2015.10.028 - DOI - PubMed
    1. Forrester JV, Kuffova L, Dick AD. Autoimmunity, autoinflammation, and infection in uveitis. Am J Ophthalmol. 2018;189:77–85. doi:10.1016/j.ajo.2018.02.019 - DOI - PubMed
    1. Willermain F, Rosenbaum JT, Bodaghi B, et al. Interplay between innate and adaptive immunity in the development of non-infectious uveitis. Prog Retin Eye Res. 2012;31(2):182–194. doi:10.1016/j.preteyeres.2011.11.004 - DOI - PMC - PubMed
    1. Lee RW, Nicholson LB, Sen HN, et al. Autoimmune and autoinflammatory mechanisms in uveitis. Semin Immunopathol. 2014;36(5):581–594. doi:10.1007/s00281-014-0433-9 - DOI - PMC - PubMed
    1. Rosenbaum JT, Bodaghi B, Couto C, et al. New observations and emerging ideas in diagnosis and management of non-infectious uveitis: a review. Semin Arthritis Rheum. 2019;49(3):438–445. doi:10.1016/j.semarthrit.2019.06.004 - DOI - PubMed

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