Remaining Rod Activity Mediates Visual Behavior in AdultRpe65^−/−mice.

Abstract

The optomotor test is a simple method of estimating the visual function and evaluating the respective contributions of rod and cone systems. This test was used to demonstrate that in Rpe65(-/-) mice, devoid of functional cones and of detectable 11-cis-retinal protein, the rods mimic cone function in part, by mediating vision in photopic conditions.

Complementation Test ofRpe65Knockout and Tvrm148

“…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 À/À mice probably rely on residual rod photoreceptor function.…”

“…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 À/À 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.…”

“…This is the first reported progressive visual acuity loss in Rpe65 mutant mice and goes well beyond previous work reporting RPE65 visual acuity. 46 Human LCA2 patients 45,47,48 have mostly intact retina architecture even at late ages, 45,47,48 so we sought to qualitatively and quantitatively examine the retina for similar phenotypes. The architecture of the retina in T À/À mice relative to Rpe65 þ/þ and T þ/À mice was strikingly normal considering the visual function deficits (Fig.…”

“…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 À/À ::Rho À/À (Rhodopsin; pure cone function) mice do not retain visual acuity, 46 suggests the residual visual acuity in T À/À mice is driven primarily by rod function. Consistent with previous work, 46,51,54 T À/À mice lost 59.9% of cones by P60 (Fig.…”

“…53 This, coupled with the fact that Rpe65 À/À ::Rho À/À (Rhodopsin; pure cone function) mice do not retain visual acuity, 46 suggests the residual visual acuity in T À/À mice is driven primarily by rod function. Consistent with previous work, 46,51,54 T À/À mice lost 59.9% of cones by P60 (Fig. 8); furthermore, many remaining cones are not functional at that age in Rpe65 À/À mice, although they can be restored to activity by reintroduction of 11-cis-retinal.…”