Abstract
Purpose: :
To investigate the cone photoreceptor loss secondary to disruption of the underlying retinal pigment epithelium (RPE) in vivo as a model of the potential mechanism of sight loss in age-related macular degeneration (AMD).
Methods: :
Sodium iodate solution was injected intraperitoneally in mice (100 mg/kg) to induce patchy RPE cell death. A transgenetic strain of mouse (B6.Cg-Tg(OPN1LW-EGFP), OPN1-EGFP) and C57BL/6 wild type mice were used in this study. The mutant mice contain cones expressing enhanced green fluorescent protein (EGFP) under control of the human long-wavelength-sensitive cone opsin promoter. Phosphate buffered saline (PBS) was injected as the control in both strains. Fundus imaging was performed at 1, 2, 4 and 7 weeks after treatment (WK1, 2, 4 and 7, respectively) with a confocal scanning laser ophthalmoscope (cSLO) using various imaging modes. These included lipofuscin-related blue (488 nm) and melanin-related near-infrared (790 nm) autofluorescence (AF), as well as near-infrared reflectance (IR, 820 nm). At WK7, electroretinography (ERG) data were recorded and all eyes were collected for histological processing.
Results: :
Compared to PBS controls, sodium iodate treated mice showed a pronounced patch-like hyperfluorescence on near-infrared fundus AF images, suggesting changes of the RPE melanin-compartment. There were faint corresponding alterations on blue AF and IR images in C57BL/6 wild type mice. The abnormal appearance was found at WK1 and remained stable until WK7. In OPN1-EGFP mice, EGFP positive cones could individually delineated on blue AF images. Detectable patchy hyperfluorescence was found at WK2. Localized loss of EGFP-expressing cones correlated well with the patchy hyperfluorescent areas on near-infrared AF recordings. Seven weeks after sodium iodate treatment, a significant decrease of a-wave and b-wave amplitudes was recorded in both strains compared to PBS controls. Retinal histology confirmed cell death in the outer nuclear layer in regions overlying the disrupted RPE at WK7.
Conclusions: :
Systemic application of sodium iodate results in RPE-alterations that can be visualized by cSLO imaging. Secondary photoreceptor loss as shown in the EGFP reporter mouse can be tracked over time in vivo, providing a useful model for potential treatments that might be developed to prevent sight loss in AMD.
Keywords: age-related macular degeneration • photoreceptors • drug toxicity/drug effects