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Topical treatment with nerve growth factor in an animal model of herpetic keratitis
Authors:Alessandro Lambiase  Marco Coassin  Nicola Costa  Paolo Lauretti  Alessandra Micera  Emiliano Ghinelli  Luigi Aloe  Paolo Rama  Stefano Bonini
Institution:(1) Interdisciplinary Center for Biomedical Research (CIR), Laboratory of Ophthalmology, University Campus Bio-Medico of Rome, Via E. Longoni, 83 00155 Rome, Italy;(2) IRCCS-G.B. Bietti Eye Foundation, Rome, Italy;(3) Faculty of Pharmacy, University “Magna Grecia” of Catanzaro, Catanzaro, Italy;(4) Institute of Neurobiology and Molecular Medicine, CNR-EBRI, Rome, Italy;(5) Ophthalmology Department, Scientific Institute San Raffaele Hospital, Milan, Italy
Abstract:Background In vitro and in vivo studies demonstrated the antiviral efficacy of nerve growth factor (NGF) and its cyto-protective effect in herpes simplex virus (HSV)-infected cells. The aims of this study were to evaluate the role of endogenous NGF in HSV corneal infection, and the effects of topical NGF treatment on herpetic keratitis. Methods Herpetic keratitis was induced in 40 rabbits with the HSV-1 McKrae strain. Animals were divided into four groups, and treated with topical neutralizing anti-NGF antibodies, NGF, acyclovir or balanced salt solution (BSS) respectively. The clinical course of HSV keratitis was evaluated and scored by slit-lamp examination. In addition, biochemical (immunohistochemistry for glycoprotein D) and molecular (nested PCR for glycoprotein D) analyses were carried out to estimate viral replication. Results Treatment with anti-NGF antibodies induced a more severe keratitis associated with increased biochemical and molecular markers of active viral replication. Two animals in this group developed lethal HSV encephalitis. Conversely, topical treatment with NGF induced a significant amelioration of clinical and laboratory parameters when compared to the BSS treated group (control). No significant differences were observed between NGF- and acyclovir-treated groups. Conclusions This study demonstrated the crucial role of endogenous NGF in herpetic keratitis. The comparable effects of NGF and acyclovir confirm the antiviral activity of NGF, and indicate a potential use of topical NGF in herpetic keratitis.
Keywords:Nerve growth factor  Herpes simplex virus  Herpetic keratitis  Antiviral therapy
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