Abstract
Abstract: :
Purpose: During the course of certain retinal degenerative (RD) diseases in humans, and in animal models, gradual loss of photoreceptors is associated with a general decrease in rod photoreceptor outer segment (ROS) length. Changes in rod flash response kinetics were investigated in a pigmented P23H rat, a proposed model for autosomal dominant retinitis pigmentosa (ADRP), at 4 wks of age. At this age, the outer nuclear layer (ON) thickness and ROS length are similar to wild–type (WT) rats, but a–wave amplitudes are significantly reduced (see companion poster, Baig–Silva and Hetling). Methods: Pigmented rats heterozygous for the P23H transgene were tested. A paired–flash electroretinogram (ERG) protocol was used to derive the full time course of the rod response to a sub–saturating (2.25 sc cd s m–2 ) test flash. The pooled derived response data (n = 4) were fitted with a function, A(t)/Amo, used previously to describe the time course of the derived rod response in mouse. Results: The times to peak of A(t)/Amo were 83 ms and 64 ms for age matched wild–type (WT) and transgenic (P23H) rats, respectively; peak amplitudes were 0.85 and 0.65, respectively. A(t)/Amo fitted to the P23H data exhibited faster development and slower recovery compared to A(t)/Amo fitted to the WT data. The integrated areas of A(t)/Amo, between 0 and 600 ms, were: 319 A ms (WT); 227 A ms (P23H); 295 A ms (P23H scaled to the peak amplitude of the WT response); where "A" represents a dimensionless amplitude index. Conclusions: The reduced integrated response (∫A(t)/Amo dt) is consistent with the reduced ERG a–wave observed at an age before significant photoreceptor degeneration is evident, and suggests a reduced response per isomerized photon. The shorter time to peak and longer recovery time are consistent with altered passive electrical properties of a small population of photoreceptors with reduced ROS length. An alternative explanation is that the reduced response involves alterations in phototransduction activation and recovery processes.
Keywords: electroretinography: non–clinical • photoreceptors • transgenics/knock–outs