April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Treatment of Experimental Autoimmune Uveoretinitis With Intravitreal Injection of Tacrolimus (fk506) Encapsulated in Liposomes
Author Affiliations & Notes
  • R. Zhang
    Ophthalmology, Fudan University, Shanghai, China
  • J. Qian
    Ophthalmology, Fudan University, Shanghai, China
  • J. Guo
    Ophthalmology, Fudan University, Shanghai, China
  • Footnotes
    Commercial Relationships  R. Zhang, None; J. Qian, None; J. Guo, None.
  • Footnotes
    Support  Shanghai board of health (No. 2007Y01)
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 6021. doi:
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      R. Zhang, J. Qian, J. Guo; Treatment of Experimental Autoimmune Uveoretinitis With Intravitreal Injection of Tacrolimus (fk506) Encapsulated in Liposomes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6021.

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Abstract

Purpose: : To evaluate the effects of intravenously injection of liposomes encapsulating tacrolimus (FK506) on experimental autoimmune uveoretinitis (EAU) in Lewis rats.

Methods: : EAU was induced in Lewis rats by subcutaneous injection of interphotoreceptor retinoid binding protein (IRBP) R16 peptide emulsified in adjuvant. Ten days later, rats were intravitreally injected with saline, tacrolimus, tacrolimus-loaded liposomes, or unloaded liposomes. Clinical signs of inflammation and ocular histological sections were observed and graded. Retinal function was evaluated by electroretinography. Tacrolimus concentration was determined in vitreous body and aqueous humor by ELISA. Ocular biodistribution of rhodamine-conjugated liposomes (Rh-Lip) was analyzed with a laser scanning confocal microscope. To evaluate the systemic effect of intravitreal injection of tacrolimus, delayed type hypersensitivity (DTH) and lymphocyte proliferation assay (LPA) were detected.

Results: : Treatment of EAU with intravitreal injection of liposomal tacrolimus significantly reduced intraocular inflammation and markedly inhibited the development of EAU as determined in clinical and histopathological analysis. No toxic effects could be detected as determined with ERG. The concentration of tacrolimus in ocular fluids remained up to 14-day-period following the liposomal tacrolimus injection. Confocal microscopy showed a transretinal distribution of the liposomal particles. DTH and LPA responses were not impaired in liposomal tacrolimus treated rats.

Conclusions: : Intravitreal injection of liposomal tacrolimus was highly effective in suppressing the process of EAU without any side effects on retinal function and systemic cellular immunity. This treatment may represent a new option for the management of intraocular inflammation.

Keywords: uveitis-clinical/animal model • drug toxicity/drug effects • immunomodulation/immunoregulation 
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