May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
The Pharmacokinetic and Toxicity Study of Intravitreal Erythropoietin (EPO) in New Zealand Albino Rabbits
Author Affiliations & Notes
  • J. Zhang
    SIBS, CAS, Shanghai, China
    Lab of Clinical Visual Science,
    Key Laboratory of Stem Cell Biology,
  • Y. Jin
    SIBS, CAS, Shanghai, China
    Key Laboratory of Stem Cell Biology,
  • Y. Zhang
    Dept. of Ophthalmology, HHFU, Shanghai, China
  • H. Weng
    Dept. of Ophthalmology, HHFU, Shanghai, China
  • W. Shi
    Dept. of Ophthalmology, SJTUSM, Shanghai, China
  • G. Xu
    Dept. of Ophthalmology, SHSU, Shanghai, China
  • S. Sinclair
    Dept. of Ophthalmol, DUCOM, Philadelphia, Pennsylvania
  • M. Yanoff
    Dept. of Ophthalmol, DUCOM, Philadelphia, Pennsylvania
  • W. Li
    SIBS, CAS, Shanghai, China
    Lab of Clinical Visual Science,
    Dept. of Ophthalmol, DUCOM, Philadelphia, Pennsylvania
  • G.-T. Xu
    SIBS, CAS, Shanghai, China
    Lab of Clinical Visual Science,
    Key Laboratory of Stem Cell Biology,
  • Footnotes
    Commercial Relationships  J. Zhang, None; Y. Jin, None; Y. Zhang, None; H. Weng, None; W. Shi, None; G. Xu, None; S. Sinclair, None; M. Yanoff, None; W. Li, None; G. Xu, None.
  • Footnotes
    Support  (1) Ministry of Science and Technology of China (2004CB720300); (2) Shanghai Science and Technology Committee Grant (04ZR14149); (3) Unrestricted Research Fund from the Clear Vision Foundation, PA, US
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5621. doi:https://doi.org/
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      J. Zhang, Y. Jin, Y. Zhang, H. Weng, W. Shi, G. Xu, S. Sinclair, M. Yanoff, W. Li, G.-T. Xu; The Pharmacokinetic and Toxicity Study of Intravitreal Erythropoietin (EPO) in New Zealand Albino Rabbits. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5621. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : It has been proved that EPO protects retinal neurons and vascular cells in rats with early diabetes. In order to further investigate the therapeutic potential of EPO, the pharmacokinetics and toxicity after intravitreal injection (IVit) of EPO were studied in rabbits.

Methods: : 104 male New Zealand albino rabbits were included in the study. For toxicity study (60 rabbits), four groups of rabbits with IVit of EPO were studied, i.e., 10U/eye, 100U/eye, or 1,000U/eye for single injection of left eye and 0.6 U/eye every month, total 6 times in left eyes. In all groups, right eyes were used as control (normal saline injection). The rabbits were examined by indirect funduscopy, ERG, and FFA at 1, 3, 7, 14, 28 days and 6 months after injection. The rabbits with single injection were killed at 2, 4 and 24 weeks, and with repeated injections were killed at 24 weeks for histological study. For pharmacokinetic study, after IVit of 5 units of EPO into the left eye, 44 rabbits were killed at 0, 1, 2, 3, 6, 12, 24, 48, 72, 168 and 336 hours, and the vitreous, aqueous, retina and serum were collected for EPO analysis with ELISA. Pharmacokinetic data like t1/2, Cmax, Tmax, MRT and AUC were calculated. The right eyes remained untreated.

Results: : At all the time points tested, anterior segment, vitreous and retina were within normal limit. No significant funduscopic and ERG change were found. The histological appearances of the retina of EPO-treated eyes remain unchanged in comparison with the control eyes. The pharmacokinetic dada showed that: the half-life times of EPO in vitreous, aqueous and serum were 3.64, 3.07 and 2.12 days, respectively. Tmax and Cmax of EPO in those compartments were 1, 24 and 12 hours, and 4,615.75, 294.31 and 1.60mIU/mL, respectively. EPO concentrations in the retina of the injected eye peaked at 6 hours following the injection, which is 1.36mIU/mg protein. The half-life of EPO in retina is 4.39 days.

Conclusions: : IVit of EPO is well tolerated by rabbit eyes. There is no significant ocular side effect observed. After IVit (5U/eye), the serum EPO levels were always low, within normal range. Therefore, IVit of EPO is a safe procedure in terms of ocular and systemic effect. Further study is required to explain that Epo protects retinal cells for a minimum of 4 weeks, with retinal Epo half-life of 4.39 days.

Keywords: ocular irritancy/toxicity testing • injection • drug toxicity/drug effects 
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