Open AccessNonvisual light responses in the Rpe65 knockout mouse: Rod loss restores sensitivity to the melanopsin system
Author(s) -
Susan E. Doyle,
Ana Maria de Lauro Castrucci,
Maureen A. McCall,
Ignacio Provencio,
Michael Menaker
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0600934103
Subject(s) - melanopsin , rpe65 , visual phototransduction , biology , intrinsically photosensitive retinal ganglion cells , knockout mouse , circadian rhythm , microbiology and biotechnology , rhodopsin , retinal , photopigment , retina , gene knockout , endocrinology , neuroscience , genetics , retinal ganglion cell , retinal pigment epithelium , biochemistry , gene , receptor
Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin (OPN4), together with rods and cones, provide light information driving nonvisual light responses. We examined nonvisual photoreception in mice lacking RPE65, a protein that is required for regeneration of visual chromophore in rods and cones. AlthoughRpe65 knockouts retain a small degree of rod function, we show here that circadian phase shifting responses inRpe65 −/− mice are attenuated far beyond what has been reported for rodless/coneless mice. Furthermore, the number of melanopsin-immunoreactive perikarya and the extent of dendritic arborizations were decreased inRpe65 knockout mice compared with controls. To assess the nature of the photoreceptive defect inRpe65 null mice, we eliminated either rods or melanopsin fromRpe65 −/− retinas by generating (i )Rpe65 −/− mice carrying a transgene (rdta ) that results in selective elimination of rods and (ii ) double knockoutRpe65 −/− ;Opn4 −/− mice. Surprisingly, rod loss inRpe65 knockout mice resulted in restoration of circadian photosensitivity. Normal photoentrainment was lost inRpe65 −/− ;Opn4 −/− mice, and, instead, a diurnal phenotype was observed. Our findings demonstrate that RPE65 is not required for ipRGC function but reveal the existence of a mechanism whereby rods may influence the function of ipRGCs.