Topical treatment with nerve growth factor in an animal model of herpetic keratitis.
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.
Lambiase
Alessandro
A
Interdisciplinary Center for Biomedical Research (CIR), Laboratory of Ophthalmology, University Campus Bio-Medico of Rome, Via E. Longoni, 83 00155, Rome, Italy.
Coassin
Marco
M
Costa
Nicola
N
Lauretti
Paolo
P
Micera
Alessandra
A
Ghinelli
Emiliano
E
Aloe
Luigi
L
Rama
Paolo
P
Bonini
Stefano
S
D000212:Acyclovir / Q000627:therapeutic use; D000287:Administration, Topical; D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D019610:Cytoprotection; D004195:Disease Models, Animal; D005260:Female; D018259:Herpesvirus 1, Human / Q000502:physiology; D007124:Immunoenzyme Techniques; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000378:metabolism; D020932:Nerve Growth Factor / Q000502:physiology / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011817:Rabbits; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D019138:Antibodies, Blocking; D000998:Antiviral Agents; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; D020932:Nerve Growth Factor; D000212:Acyclovir