May 2003
Volume 44, Issue 13
ARVO Annual Meeting Abstract  |   May 2003
In Vivo Transscleral Delivery of FITC-Conjugated Molecules to the Rabbit Choroid and Retina
Author Affiliations & Notes
  • I.K. Rigas
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, MA, United States
  • P. Calias
    Eyetech Research Center, Woburn, MA, United States
  • K.G. Karrasquillo
    Eyetech Research Center, Woburn, MA, United States
  • E.S. Gragoudas
    Eyetech Research Center, Woburn, MA, United States
  • J.W. Miller
    Eyetech Research Center, Woburn, MA, United States
  • A.P. Adamis
    Eyetech Research Center, Woburn, MA, United States
  • Footnotes
    Commercial Relationships  I.K. Rigas, Eyetech Pharmaceuticals P; P. Calias, Eyetech Pharmaceuticals P; K.G. Karrasquillo, Eyetech Pharmaceuticals P; E.S. Gragoudas, Eyetech Pharmaceuticals P; J.W. Miller, Eyetech Pharmaceuticals P; A.P. Adamis, Eyetech Pharmaceuticals P.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 4432. doi:
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      I.K. Rigas, P. Calias, K.G. Karrasquillo, E.S. Gragoudas, J.W. Miller, A.P. Adamis; In Vivo Transscleral Delivery of FITC-Conjugated Molecules to the Rabbit Choroid and Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4432.

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

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Abstract: : Purpose: To study the in vivo kinetics of various FITC-conjugated compounds through the sclera to the choroid and retina. Methods: A small polypropylene plastic chamber was attached to the bare scleral surface of anesthetized Dutch-belted rabbits with cyanoacrylate glue and loaded with 15ug of FITC-conjugated 10 kDa and 40 kDa dextrans. Transscleral diffusion of the molecules into the orbit, aqueous, vitreous, choroid, retina and peripheral blood was quantified at 24, 48, 72 and 120hrs (5 days) with the use of fluorophotometry. All measurements were corrected for tissue autofluorescence by comparison to the fellow eye. Scleral flat mounts were examined under a fluorescent microscope and the transscleral diffusion pattern was visualized. Results: The dextran concentration in the choroid and in the retina peaked at 24hrs (10kDa: choroid: 57± 3.8ug/ml p=0.0001, retina: 9.91±2ug/ml p=0.001 and 40kDa: choroid: 35.95±2.39ug/ml p=0.0001, retina: 7.43±1.72ug/ml p=0.003) and remained elevated even after 5 days (10kDa: choroid: 8.43±0.89ug/ml p=0.0003, retina: 1.84±0.25ug/ml p=0.001 and 40kDa: choroid: 5.23±1ug/ml p=0.001, retina: 1.71±0.55ug/ml p=0.007), n=7 for 24hrs and n=5 for 120hrs. At 24hrs, the 10kDa dextran had better penetration in the choroid and retina compared to the 40kDa (20% versus 12% of the total, respectively) and at the same time point there was a linear relationship between molecular weight and tissue penetration. In all other tissues, the amounts of the FITC-compounds were negligible, confirming the selective nature of this drug delivery system. Conclusions: With the use of an established experimental animal model, we have studied the kinetics of transscleral delivery of compounds with differing molecular weights. These data demonstrate that molecular weight may be a possible predictor for tissue penetration. Overall, transscleral drug delivery achieves potentially therapeutic levels within the choroid and retina.

Keywords: sclera • choroid • retina 

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