Enhanced cone dysfunction in rats homozygous for the P23H rhodopsin mutation.
The heterozygous P23H transgenic rat is a model of autosomal dominant retinitis pigmentosa, in which a mutation in the rhodopsin gene leads to a rapid loss of rods and a more protracted loss of cones. It has been suggested that rods play an essential role in preserving cones. We tested this hypothesis by examining whether higher levels of dysfunctional rhodopsin in rats homozygous for the P23H mutation would result in exacerbated cone dysfunction when compared with heterozygous P23H rats. Electroretinogram (ERG) responses were recorded from P21 to P250 in Sprague-Dawley (SD) and homozygous P23H rats. Both scotopic and photopic intensity response ERGs were severely depressed already at P21 when compared with age-matched SD rats. Furthermore, flicker amplitudes and critical fusion frequencies were also lower in P23H compared with SD rats at P21. Scotopic and photopic intensity responses as well as flicker amplitude and critical fusion frequencies declined rapidly up to P60, reaching a steady state that was maintained up to P200. We conclude that in rats homozygous for P23H rhodopsin mutations, the severe loss of rod function already seen by P21 is accompanied by substantial cone functional loss at that age. While rod-related responses are more severely affected than cone-related responses at all ages, their actual rate of decline with age is surprisingly similar. Both undergo a biphasic temporal pattern of decline: very rapid (P21-P60) followed by very slow (P60-P200) deterioration in response parameters, implying a tight link between rod and cone functional deterioration.
Pinilla
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Moran Eye Center, Ophthalmology and Visual Sciences, University of Utah, 75 North Medical Drive, Salt Lake City, UT 84132, USA.
Lund
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RD
Sauvé
Y
Y
D000375:Aging / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D004596:Electroretinography; D005425:Flicker Fusion; D006720:Homozygote; D008297:Male; D009154:Mutation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000254:growth & development; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D012162:Retinal Degeneration / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D012243:Rhodopsin / Q000235:genetics* / Q000502:physiology
D012243:Rhodopsin