The visual acuity of T
−/− mice is surprisingly high (almost normal) at early ages (
Fig. 4) considering the lack of 11-
cis-retinal generation in RPE65-deficient mice
2,43 ; neither
Rpe65KO nor
Rpe65rd12 mice have detectable amounts of 11-
cis-retinal in the retina.
2,43 Rpe65R91W mice have ∼5% the wild type amount of 11-
cis-retinal in the retina, and this residual enzymatic product is sufficient to preserve vision significantly longer than what is seen in other
Rpe65 mutant mice.
44 We show tvrm148 mice lack 11-
cis-retinal altogether (
Table 2). The residual visual function in T
−/− mice may correspond to residual rod function, not cone function
42,49 because in the absence of 11-
cis-retinal, cone opsins in mice mislocalize,
50,51 and it has been proposed this cone opsin mislocalization may have a toxic effect on cone cells.
51 Work with rd12 mice shows most cones are lost from the retina by P30.
46 This is in contrast to most other retinal degenerations reported in mice in which visual function loss is driven primarily by rod photoreceptor loss.
46 Visual acuity measurements are performed in photopic conditions that are dominated by cone photoreceptors in C57BL/6J mice,
52 so it may at first seem counterintuitive that the visual acuity measurements in T
−/− mice probably rely on residual rod photoreceptor function. Previous work shows the greatly altered kinetics of rod photoreceptors in
Rpe65 knockout mice cause them to function exclusively in photopic conditions because of reduced photon quantum-catch capability.
53 This, coupled with the fact that
Rpe65−/− ::
Rho−/− (
Rhodopsin; pure cone function) mice do not retain visual acuity,
46 suggests the residual visual acuity in T
−/− mice is driven primarily by rod function. Consistent with previous work,
46,51,54 T
−/− mice lost 59.9% of cones by P60 (
Fig. 8); furthermore, many remaining cones are not functional at that age in
Rpe65−/− mice, although they can be restored to activity by reintroduction of 11-
cis-retinal.
55