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Haidong Shan, Peter C. Issa, Sher A. Aslam, Alun R. Barnard, Robert E. MacLaren; Cone Photoreceptor Death Occurring Secondary To Retinal Pigment Epithelium Loss Assessed In Vivo In Transgenic Fluorescent Reporter Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1141.
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© ARVO (1962-2015); The Authors (2016-present)
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).
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.
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.
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.
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