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(Investigative Ophthalmology and Visual Science. 2005;46:3800-3806.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-0301
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Pharmacokinetics of Conjunctivally Applied Nerve Growth Factor in the Retina and Optic Nerve of Adult Rats

Alessandro Lambiase,1,2 Paola Tirassa,3 Alessandra Micera,2 Luigi Aloe,3 and Stefano Bonini1,2

1From the Interdisciplinary Research Center, Laboratory of Ophthalmology, University of Rome "Campus Bio-Medico," Rome, Italy; the 2G. B. Bietti Eye Foundation, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy; and the 3Institute of Neurobiology and Molecular Medicine, National Research Council, Rome, Italy.

PURPOSE. Nerve growth factor (NGF) has been shown to inhibit retinal ganglion cell (RGC) degeneration when injected intraocularly in animal models of ocular hypertension, optic nerve transaction, and ischemia. The present study sought to establish the bioavailability of topical NGF to the retina and optic nerve in rats.

METHODS. Autoradiography was performed to evaluate whether exogenous 125I-labeled NGF reaches the retina and optic nerve when applied topically to the rat conjunctiva. To quantify NGF levels, a highly specific immunoenzymatic test (ELISA) was performed on the retina, optic nerve, lens, sclera and serum of rats at different time points after administration of NGF (1–500 µg/mL). The physiological activity of topically applied NGF was evaluated by determining retinal brain-derived neurotrophic factor (BDNF) protein and mRNA levels by ELISA and RT-PCR, respectively.

RESULTS. After topical conjunctival administration of NGF, high levels were detected in ocular tissues, including the retina and optic nerve, showing a peak increase 6 hours after administration at a concentration of 200 µg/mL. NGF treatment was associated with an increase in BDNF protein and mRNA levels in rat retina.

CONCLUSIONS. These data demonstrate the bioavailability of NGF to the retina and optic nerve in rats when administered topically. These findings justify investigating the clinical effects of topical NGF therapy for treatment of posterior segment diseases.






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