June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Topically Administered Mouse IgG1 Accumulates In the Rat Optic Nerve And Retina
Author Affiliations & Notes
  • Stacy Hu
    Biomedical Sciences and Disease, New England College of Optometry, Boston, MA
  • Steven Koevary
    Biomedical Sciences and Disease, New England College of Optometry, Boston, MA
  • Footnotes
    Commercial Relationships Stacy Hu, None; Steven Koevary, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1077. doi:
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      Stacy Hu, Steven Koevary; Topically Administered Mouse IgG1 Accumulates In the Rat Optic Nerve And Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1077.

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

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Purpose: Frequent intravitreal injections of monoclonal anti-VEGF agents Lucentis and Avastin were shown to reverse the effects of wet AMD. These injections, however, predispose patients to endophthalmitis and stroke, among other ocular and systemic adverse effects. Such complications, as well as patient discomfort, would be potentially reduced or even eliminated by the delivery of these drugs in mist or drop form. The purpose of this study was to obtain pilot data regarding the feasibility of delivering potentially therapeutic large, hydrophilic antibodies to the posterior pole by eye drop application.

Methods: Female Lewis rats received a single 25 mg/10 µL topical dose of whole mouse monoclonal IgG1 antibody in PBS without a permeation enhancer into one eye; control rats were left untreated. The concentration of IgG1 was determined in retinal and optic nerve homogenates 10 to 20 minutes later using an ELISA; tissues were homogenized in lysis buffer containing protease inhibitors. Data are expressed as the mean concentration±SEM and were analyzed using the Kruskal-Wallis test. Serum IgG1 levels were also determined.

Results: Mouse IgG1 levels in the optic nerve were elevated 10 (n=16) and 20 (n=15) minutes after application (11.2±1.8 and 5.8±0.8 ng/mL of clarified homogenate, respectively) relative to control rats (n=15; 3.8±0.6 ng/mL, p=0.0004 and 0.062, respectively). Mouse IgG1 levels in the retina were significantly elevated after an average of 15 minutes (n=31; 3.1±0.6 ng/µg tissue) relative to control rats (n=15; 1.3±0.2 ng/μg, p=0.02). Serum IgG1 levels 10 and 20 minutes after application (both 0.3±0.1 ng/mL) were insignificantly different from levels seen in control rats (0.2±0.2 ng/mL; p=0.52).

Conclusions: Mouse IgG1, applied topically in rats, accumulated in the retina and optic nerve. As in our previous studies with insulin, leptin, and GDNF, IgG1 levels peaked in the optic nerve earlier than in the retina, supporting the hypothesis that topically applied compounds traverse the sclera to reach the posterior pole. Notably, IgG1 application did not result in appreciable uptake into peripheral blood, suggesting that topical treatment with anti-VEGF antibodies would not contribute to the development of systemic complications.

Keywords: 503 drug toxicity/drug effects • 629 optic nerve • 688 retina  

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