May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Leptin Drops but Not Leptin-Containing Implants Result in the Accumulation of Leptin in the Hypothalamus of Rats
Author Affiliations & Notes
  • S. B. Koevary
    Biomedical Science & Disease, New England Coll of Optometry, Boston, Massachusetts
  • J. Y. Lee
    Biomedical Science & Disease, New England Coll of Optometry, Boston, Massachusetts
  • C. Robinson
    Biomedical Science & Disease, New England Coll of Optometry, Boston, Massachusetts
  • P. Mayo
    Biomedical Science & Disease, New England Coll of Optometry, Boston, Massachusetts
  • Footnotes
    Commercial Relationships S.B. Koevary, None; J.Y. Lee, None; C. Robinson, None; P. Mayo, None.
  • Footnotes
    Support NEI R24 EY014817 HIGHWIRE EXLINK_ID="48:5:5812:1" VALUE="EY014817" TYPEGUESS="GEN" /HIGHWIRE ; Massachusetts Lions Eye Research Fund
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5812. doi:
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    • Get Citation

      S. B. Koevary, J. Y. Lee, C. Robinson, P. Mayo; Leptin Drops but Not Leptin-Containing Implants Result in the Accumulation of Leptin in the Hypothalamus of Rats. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5812.

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

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Abstract

Purpose:: Our previous data showed that the application of leptin-containing eye drops resulted in its accumulation in the hypothalamus of rats. We theorized that delivery of leptin in this manner to its CNS target might be useful in reducing appetite and body weight in obese individuals who display blood-brain-barrier resistance to leptin. However, our previous data also showed that such treatment failed to influence the body weight or food intake of rats. Since this lack of effect may have been due to the penetration through the eye of insufficient amounts of leptin, we theorized that the more sustained release of leptin from an ocular implant might be more efficacious in this regard. In this study, we examined the effects of leptin-containing ethylene vinyl acetate copolymer ocular implants on the delivery of leptin into the hypothalamus.

Methods:: In an initial experiment, we loaded 2 mg pieces of the above copolymer with 10 micrograms of leptin and then incubated them in microtiter wells, after which we removed aliquots at various time points and measured their leptin concentrations. In a second experiment, we cultured leptin-containing implants for 1 hour following their 30 minute incubation in the rats’ ocular cul-de-sac and measured their ability to release peptide into the supernatants. Finally, we compared hypothalamic leptin levels in rats 30 minutes and 2 hours after they received a 10 microliter drop of a 1.25 mg/ml solution of leptin to those that harbored a leptin containing implant for the same lengths of time. Leptin levels were quantified by ELISA and tissues levels were expressed as pg of leptin/mg protein.

Results:: Cultured, leptin-containing implants released markedly elevated amounts of leptin over the first 2 hours (>9 ng/ml), and reduced levels at 3 and 4 hours. Animals treated with leptin eye drops displayed significantly elevated leptin concentrations in the hypothalamus at 30 minutes (p<0.03). On the other hand, hypothalamic leptin levels were not significantly elevated in the implant group at either 30 minutes or 2 hours post-implantation. However, these implants released 11.2+0.9 micrograms/ml of leptin over the course of 1 hour after they were removed from the eyes of rats that housed them for 30 minutes.

Conclusions:: Our results showed that while leptin inserts had the ability to release large amounts of leptin, at least over the course of 2 hours, they were ineffective in delivering leptin to the hypothalamus.

Keywords: drug toxicity/drug effects 
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