title: HPMPC therapy of MCMV-induced retinal disease in the SCID mouse measured by electroretinography, a non-invasive technique.
abstract: The purpose of these studies was to investigate the use of non-invasive electroretinography for the evaluation of retinal disease and its treatment in an ocular murine cytomegalovirus (MCMV) disease model. While under anesthesia, 10(2.6)plaque forming units (pfu) of salivary gland passaged, Smith strain MCMV was injected in the anterior chamber of 6- to 8-week-old severe combined immunodeficiency (SCID) mice. At various times post-inoculation, bright-flash scotopic electroretinogram, viral titer, and histology were obtained from the injected eye. Antiviral therapy was tested using 0.1 and 5mg/kg/day subcutaneous injections of HPMPC (Cidofovir) once daily for 5 consecutive days. In infected animals, the a- and b-waves of the electroretinographic (ERG) signal were significantly reduced as of 10 days post-inoculation when compared to control animals. Therapy with HPMPC 0.1mg/kg/day subcutaneously (s.c.) once daily for 5 consecutive days was able to delay the decrease in ERG wave amplitude and inhibit viral replication, whereas 5mg/kg/day s.c. significantly protected the ERG, completely inhibited viral replication, and maintained ocular viral titer below the limit of detection for up to 17 days post-infection. The reduction of ERG activity during progression of retinal disease correlated well with reduction of disease pathology. ERG recording represents a valuable non-invasive technique to measure the progression of the retinal disease induced by MCMV and the efficacy of antiviral treatment in the ocular MCMV disease model.
authors.affiliation: Boehringer Ingelheim (Canada) Ltd Research and Development, 2100 Cunard Street, Laval,Québec, Canada H7S 2G5. mgaeneau@lav.boehringer-ingellheim.com
authors.forename: Michel
authors.initials: M
authors.lastname: Garneau
authors.forename: Gordon T
authors.initials: GT
authors.lastname: Bolger
authors.forename: Christiane
authors.initials: C
authors.lastname: Bousquet
authors.forename: Philip
authors.initials: P
authors.lastname: Kibler
authors.forename: François
authors.initials: F
authors.lastname: Tremblay
authors.forename: Michael G
authors.initials: MG
authors.lastname: Cordingley
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000077404:Cidofovir; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy* / Q000821:virology; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004596:Electroretinography / Q000379:methods; D015828:Eye Infections, Viral / Q000188:drug therapy / Q000821:virology; D005260:Female; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000821:virology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D018146:Muromegalovirus / Q000472:pathogenicity*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D012160:Retina / Q000821:virology; D016896:Treatment Outcome; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir