Construction of a mouse model of Posner-Schlossman syndrome by anterior chamber infection with cytomegalovirus

Abstract

Accumulated clinical evidence has shown that Posner-Schlossman syndrome (PSS) is most likely the result of recurrent human cytomegalovirus (HCMV) infection in the anterior chamber (AC). Establishing an animal model is necessary to investigate the pathogenesis of PSS. In this study, we constructed a mouse model of (PSS) by injecting murine cytomegalovirus (MCMV) into the AC of BALB/c mice. Twenty-five BALB/c mice were divided into 5 groups. Smith strain MCMV expressing enhanced green fluorescent protein (EGFP) was passaged with mouse embryonic fibroblast (MEF). Right eyes in the 4 experiment groups received AC injection of 1 μL of virus solution with concentrations of 10³,10⁴,10⁵,10⁶ pfu/mL respectively, and the control group received only PBS. PSS-like signs (mutton-fat keratic precipitates (KP), pupil dilation, IOP elevation and corneal edema) were recorded 0-28 days post-injection (DPI). Sections of eyeballs from another 9 mice harvested on 0,10 and 28 DPI were examined to locate KP and the fluorescence signal of the virus. Reversible PSS-like signs except KP were observed in 20% and 60% mice of 10⁴ and 10⁵ groups while no PSS-like signs in the control and 10³ group; 80% in the 10⁶ group with partially unreversible signs till 28DPI. Much More fluorescent signals of virus in the iris and KP were found on 10DPI than 28 DPI, while no fluorescent signals and KP on 0DPI. The extent of PSS-like signs (pupil dilation, IOP elevation and corneal edema) was virus concentration-dependent (Spearman correlation coefficient, r = 0.830, = 0.475, = 0.662, p < 0.0001, <0.05, <0.001, respectively, n = 25). Success rate of PSS model (mice with PSS-like signs) was also virus concentration-dependent (Chi-square trend test, χ² = 6.828, df = 1, p < 0.01, n = 25). Our results indicate that AC injection of 1 μL MEF passaged MCMV (Smith strain) of 10⁴-10⁶ pfu/mL in BALB/c mice can be used to construct a mouse model of PSS. MCMV can infect iris tissue and replicate in it and then establish latency. This might account for the recurrent and self-limited nature of PSS.

Keywords: Animal model; Cytomegalovirus; Etiology; Intraocular pressure; Pathogenesis; Posner-Schlossman syndrome.