Discordant anatomical, electrophysiological, and visual behavioral profiles of retinal degeneration in rat models of retinal degenerative disease.
OBJECTIVE
To assess structural, functional, and visual behavioral relationships in mutant rhodopsin transgenic (Tg) rats and to determine whether early optokinetic tracking (OKT) visual experience, known to permanently elevate visual thresholds in normal rats, can enhance vision in rats with photoreceptor degeneration.


METHODS
Eight lines of pigmented Tg rats and RCS rats were used in this study. OKT thresholds were tested at single ages (1, 2, 3, 4, and 6 months) in naïve groups of rats, or daily in groups that began at eye-opening (P15) or 10 days later (P25). Electroretinogram (ERG) response amplitudes were recorded after OKT testing, and outer nuclear layer (ONL) thickness measurements were then obtained.


RESULTS
OKT thresholds, when measured at a single time point in naïve Tg lines beginning at P30, did not decline until months after significant photoreceptor loss. Daily testing of Tg lines resulted mostly with OKT thresholds inversely related to photoreceptor degeneration, with rapid degenerations resulting in sustained OKT thresholds for long periods despite the rapid photoreceptor loss. Slower degenerations resulted in rapid decline of thresholds, long before the loss of most photoreceptors, which was even more pronounced when daily testing began at eye opening. This amplified loss of function was not a result of testing-induced damage to the rod or cone photoreceptors, as ERG amplitudes and ONL thicknesses were the same as untested controls.


CONCLUSIONS
The unexpected lack of correlation of OKT testing with photoreceptor degeneration in the Tg rats emphasizes the need in behavioral therapeutic studies for careful analysis of visual thresholds of experimental animals prior to therapeutic intervention.
Department of Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, Oregon, USA. mcgilltr@ohsu.edu
Trevor J
TJ
McGill
Glen T
GT
Prusky
Robert M
RM
Douglas
Douglas
D
Yasumura
Michael T
MT
Matthes
Robert J
RJ
Lowe
Jacque L
JL
Duncan
Haidong
H
Yang
Kelly
K
Ahern
Kate M
KM
Daniello
Byron
B
Silver
Matthew M
MM
LaVail
D000818:Animals; D004195:Disease Models, Animal; D004596:Electroretinography; D009154:Mutation; D051381:Rats; D055647:Rats, Transgenic; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D012243:Rhodopsin / Q000235:genetics; D012684:Sensory Thresholds / Q000502:physiology; D014796:Visual Perception / Q000502:physiology*
D012243:Rhodopsin