Pharmacokinetics of conjunctivally applied nerve growth factor in the retina and optic nerve of adult rats

Alessandro Lambiase, Paola Tirassa, Alessandra Micera, Luigi Aloe, Stefano Bonini

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)3800-3806
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume46
Issue number10
DOIs
Publication statusPublished - Oct 2005

ASJC Scopus subject areas

  • Ophthalmology

Fingerprint Dive into the research topics of 'Pharmacokinetics of conjunctivally applied nerve growth factor in the retina and optic nerve of adult rats'. Together they form a unique fingerprint.

Cite this