Pharmacokinetics of conjunctivally applied nerve growth factor in the retina and optic nerve of adult rats.
OBJECTIVE
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 (125)I-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 microg/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 mug/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.
Lambiase
Alessandro
A
Interdisciplinary Research Center, Laboratory of Ophthalmology, University of Rome Campus Bio-Medico, Italy. a.lambiase@unicampus.it
Tirassa
Paola
P
Micera
Alessandra
A
Aloe
Luigi
L
Bonini
Stefano
S
D000287:Administration, Topical; D000818:Animals; D001345:Autoradiography; D001682:Biological Availability; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003228:Conjunctiva / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D020932:Nerve Growth Factor / Q000235:genetics / Q000493:pharmacokinetics*; D009900:Optic Nerve / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D020932:Nerve Growth Factor