To summarize the relative degeneration rates, ONL thicknesses were
plotted as a function of time. In
GHL
+ rho +/+ retinas,
the rod degeneration was slow but complete by P210 (
Fig. 6A ). When both normal rhodopsin alleles were absent, the degeneration was
much faster and essentially complete at P60. Degenerations in
rho −/− and
GHL
+ rho +/+ retinas
progressed at nearly the same rate.
Rho −/− rods,
however, never formed an outer segment, whereas
GHL
+ rho +/+ rods did.
To correlate ONL thickness with function, ERGs from individual
rho −/− and
rho +/− mice, as well as
GHL
+ rho −/− and GHL
+ rho +/+ mice
were studied as a function of age. Transgene expression on a null
background led to an early and severe loss of rod function; scotopic
(rod) ERG a- and b-wave amplitudes of the P30
GHL
+ rho −/− mouse were not recordable, consistent with absence of
ROSs.
17 Decay of ERG b-wave amplitudes as a function of
age up to P180 is summarized for scotopic
(Fig. 6B) and photopic
(Fig. 6C) conditions. Scotopic b-wave responses of
rho −/− mice
vanished at P90. Decline of scotopic responses of
GHL
+ rho +/+ mice was
slower, with a well detectable response at P90. In contrast, scotopic
responses of heterozygotes attained a high level, even at P180, and
thereafter showed a moderate decline. The photopic response of the
GHL
+ rho −/− mouse, most likely reflecting cone activity, was barely detectable at
P30. Decay of
rho −/− and
GHL
+ rho +/+ photopic
responses occurred at similar rates. The results show that mitigation
of degeneration occurring with GHL transgene expression was correlated
with wild-type rhodopsin gene copy number. Overall, degeneration
occurred with the following order of severity:
GHL
+ rho −/−>
GHL
+ rho +/− >
rho −/− ∼
GHL
+ rho +/+ >
rho +/− >
rho +/+.