April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Ocular Biodistribution of a Single-Chain Antibody Fragment Directed Against Tumor Necrosis Factor Alpha (tnf Alpha), Following Topical Administration in the Rabbit
Author Affiliations & Notes
  • M. Berdugo-Polak
    INSERM U872, Paris, France
    Les Cordeliers, Université Pierre et Marie Curie Paris6, Université Paris Descartes, Paris, France
  • E. Furrer
    ESBATech AG, Schlieren, Switzerland
  • C. Stella
    University of Geneva, Geneva, Switzerland
  • R. Gurny
    University of Geneva, University of Lausanne, Geneva, Switzerland
  • U. Feige
    ESBATech AG, Schlieren, Switzerland
  • P. Lichtlen
    ESBATech AG, Schlieren, Switzerland
  • D. M. Urech
    ESBATech AG, Schlieren, Switzerland
  • F. Behar-Cohen
    INSERM U872, Paris, France
    Hôtel-Dieu University Hospital, Paris, France
  • Footnotes
    Commercial Relationships  M. Berdugo-Polak, None; E. Furrer, ESBATech, E; C. Stella, None; R. Gurny, None; U. Feige, ESBATech AG, E; P. Lichtlen, ESBATech AG, E; D.M. Urech, ESBATech AG, E; F. Behar-Cohen, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5993. doi:
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      M. Berdugo-Polak, E. Furrer, C. Stella, R. Gurny, U. Feige, P. Lichtlen, D. M. Urech, F. Behar-Cohen; Ocular Biodistribution of a Single-Chain Antibody Fragment Directed Against Tumor Necrosis Factor Alpha (tnf Alpha), Following Topical Administration in the Rabbit. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5993.

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

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Purpose: : To evaluate biodistribution and pharmacokinetics of a single-chain antibody fragment directed at TNF alpha (named ESBA 105) onto the rabbit eyeball, following various topical administration regimens.

Methods: : New Zealand White rabbits received either ten topical drops of ESBA 105 within one single day or five drops a day during up to 6 days. Control group received the same cumulative dose of ESBA 105 intraveinously. After sacrifice and enucleation, aqueous, vitreous, neuroretina and RPE/choroid of both treated and non-treated eyes and sera were collected. For each sample, ESBA 105 concentration was quantified by ELISA and Cmax was determined.

Results: : High frequency one-day topical treatment allowed ESBA 105 to penetrate into the eye: when cumulative administered dose was 5 mg per eye, the concentration measured was above 10 ng/ml in the aqueous and above 100 ng/ml in the vitreous, neuroretina and RPE/choroid. Systemic administration allowed higher ESBA 105 concentrations in sera, aqueous and RPE/choroid and lower concentrations in vitreous and neuroretina. Topical application was more efficient to reach the posterior segment than the aqueous humor. The contralateral untreated eye intraocular biodistribution parraleled that of the treated eye but at a lower and delayed level. Following multi-day topical dosing (up to 15 mg administered), the higher intraocular ESBA 105 concentration was found in the RPE-choroid (1298 ng/ml), the lower one in the aqueous (153 ng/ml) and all the studied compartment were reached; whereas in the serum, ESBA 105 concentration did not exceed 3 ng/ml at 1 day and was not detectable later.

Conclusions: : Topically administered ESBA 105 seems an interesting compound for treatment of both acute and chronic TNF alpha-related ocular diseases.

Keywords: inflammation • pathology: experimental • pathobiology 

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