Topical treatment with nerve growth factor in an animal model of herpetic keratitis |
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Authors: | Alessandro Lambiase Marco Coassin Nicola Costa Paolo Lauretti Alessandra Micera Emiliano Ghinelli Luigi Aloe Paolo Rama Stefano Bonini |
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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 |
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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. |
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Keywords: | Nerve growth factor Herpes simplex virus Herpetic keratitis Antiviral therapy |
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