June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Characterization of the pH and Temperature in the Rabbit Vitreous: Key Parameters for the Development of Long Acting Delivery of Drugs to the Posterior Segment of the Eye
Author Affiliations & Notes
  • Florence LORGET
    Genentech, South San Francisco, CA
  • Chris Schuetz
    Genentech, South San Francisco, CA
  • Simon Authier
    CiToxLAB, Laval, QC, Canada
  • Michel Carrier
    CiToxLAB, Laval, QC, Canada
  • Audrey Parenteau
    CiToxLAB, Laval, QC, Canada
  • Ann Daughety
    Genentech, South San Francisco, CA
  • Vladimir Bantseev
    Genentech, South San Francisco, CA
  • Evan A. Thackaberry
    Genentech, South San Francisco, CA
  • Footnotes
    Commercial Relationships Florence LORGET, Genentech (E); Chris Schuetz, genentech (E); Simon Authier, CiToxLAB (E); Michel Carrier, CiToxLAB (C); Audrey Parenteau, CiToxLAB (E); Ann Daughety, Genentech (E); Vladimir Bantseev, Genentech (E); Evan Thackaberry, Genentech (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 146. doi:
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      Florence LORGET, Chris Schuetz, Simon Authier, Michel Carrier, Audrey Parenteau, Ann Daughety, Vladimir Bantseev, Evan A. Thackaberry; Characterization of the pH and Temperature in the Rabbit Vitreous: Key Parameters for the Development of Long Acting Delivery of Drugs to the Posterior Segment of the Eye. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):146.

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

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Abstract

Purpose: Intravitreal injection is the main route of administration for agents targeting disorders of the posterior segment of the eye such as age-related macular degeneration (AMD) and diabetic macular edema (DME). Current therapies require monthly or every other month administration. Reducing the frequency of dosing (e.g. every 4 to 6 months) thanks to sustained delivery of the therapeutic agent would present significant clinical benefits.<br /> Characterizing the micro-environment and understanding the physiology of the vitreous are paramount in developing strategies for sustained drug delivery in this tissue. Many of these strategies rely on pH- and/or temperature-driven release of the drug. However, these parameters, in particular regional changes, are poorly characterized in ocular animal models.<br />

Methods: Using anesthetized white New Zealand rabbits, we characterized both pH and temperature in several locations in the vitreous and one in the aqueous. We also established postmortem pH changes.

Results: Our data showed several gradients of temperature across the vitreous. Along the central axis, temperatures were higher in the medial vitreous (38.2 C) versus the lateral vitreous (35.8 C). Temperatures were also higher caudally close to the retina (37.7 C) than rostrally near the lens (36.2 C). Finally, a similar gradient was observed from the ventral to dorsal vitreous. Smaller gradients were observed for pH along the dorsal/ventral (7.37 versus 7.29) axis and the medial/lateral axis (7.27 versus 7.36). As compared to the central vitreous (36.9 C and 7.29), the temperature in the aqueous humor was significantly lower (33.7 C), while the pH was significantly higher (7.52). Rapid pH decreases were observed postmortem (pH 6.56, 90 minutes after euthanasia).

Conclusions: Results show regional temperature and pH differences in the vitreous of healthy adult rabbits. These differences need to be factored into strategies for developing biodegradable long acting delivery systems.

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