Intravitreal acyclovir in rabbit eyes: a pharmacological, electrophysiological, immunocytochemical and morphological study

• Grant number: 11/06924-4
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2011
• End date: September 30, 2014
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Dora Selma Fix Ventura
• Grantee: Dora Selma Fix Ventura
• Host Institution: Instituto de Psicologia (IP). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Francisco Max Damico

Abstract

Acute retinal necrosis (ARN) is a devasting viral infection of the retina. Intravenous acyclovir is the drug of choice for its selectivity against herpes simplex virus and varicella-zoster vírus. However, clinical studies show that its concentration in the vitreous after oral intake is very low. We postulate that intravitreal injection of acyclovir may better control this type of aggressive retinitis by delivering acyclovir directly inside the infected eye as soon as the diagnosis is established. Less retinal destruction may allow better visual outcome and smaller risk for retinal detachment.The aims of this study are: (1) To determine acyclovir half-life after intravitreal injection in the vitreous in two conditions (normal vitreous and after vitreous liquefaction using hyaluronidase); (2) To determine the effect of intravitreal acyclovir on the rabbit retinal function; (3) To evaluate acyclovir effect in the expression of retinal apoptosis marquers and retinal cellular proliferation; and (4) To determine the morphological effects of intravitreal acyclovir on the rabbit retina.Acyclovir half-life in the vitreous before and after vitreous liquefaction will be determined by high-performance liquid chromatography. Animals will be sacrificed 1, 7, 14 and 28 days after intravitreal injection of acyclovir. Functional retinal changes will be assessed by electroretinography. Retinal expression of retinal apoptosis marquers and retinal cellular proliferation will be determined by TUNEL and immunohistochemistry. Morphological retinal findings will be assessed by light microscopy.Intravitreal injection of acyclovir may be an important tool for the treatment of ARN as this highly specific antiviral drug will be directly delivered inside the eye with prompt action. The experimental study in rabbit eyes of this new route for acyclovir delivery to the retina to treat retinal viral infections may be the first step before this approach may be used in pré-clinical studies. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FRANCISCO MAX DAMICO; MARIANA RAMOS SCOLARI; GABRIELA LOURENÇON IOSHIMOTO; BEATRIZ SAYURI TAKAHASHI; ARMANDO DA SILVA CUNHA JR.; SÍLVIA LIGÓRIO FIALHO; DANIELA MARIA BONCI; FABIO GASPARIN; DORA FIX VENTURA. Vitreous pharmacokinetics and electroretinographic findings after intravitreal injection of acyclovir in rabbits. Clinics, v. 67, n. 8, p. 931-937, 2012-08-00. (11/06924-4, 10/08331-8, 08/58731-2)