In vivo analysis of onset and progression of retinal degeneration in the Nr2e3 mouse model of enhanced S-cone sensitivity syndrome.

The photoreceptor-specific nuclear receptor Nr2e3 is not expressed in Nr2e3 mice, a mouse model of the recessively inherited retinal degeneration enhanced S-cone sensitivity syndrome (ESCS). We characterized in detail C57BL/6J Nr2e3 mice in vivo by fundus photography, optical coherence tomography and fluorescein angiography and, post mortem, by histology and immunohistochemistry. White retinal spots and so-called 'rosettes' first appear at postnatal day (P) 12 in the dorsal retina and reach maximal expansion at P21. The highest density in 'rosettes' is observed within a region located between 100 and 350 µM from the optic nerve head. 'Rosettes' disappear between 9 to 12 months. Non-apoptotic cell death markers are detected during the slow photoreceptor degeneration, at a rate of an approximately 3% reduction of outer nuclear layer thickness per month, as observed from 7 to 31 months of age. In vivo analysis of Nr2e3 Cx3cr1 retinas identified microglial cells within 'rosettes' from P21 on. Subretinal macrophages were observed in vivo and by confocal microscopy earliest in 12-months-old Nr2e3 retinas. At P21, S-opsin expression and the number of S-opsin expressing dorsal cones was increased. The dorso-ventral M-cone gradient was present in Nr2e3 retinas, but M-opsin expression and M-opsin expressing cones were decreased. Retinal vasculature was normal.