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Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms.

Göz D, Studholme K, Lappi DA, Rollag MD, Provencio I, Morin LP - PLoS ONE (2008)

Bottom Line: Intravitreal injection of this immunotoxin results in targeted destruction of melanopsin cells.In particular, the photosensitivity of the circadian system is significantly attenuated.This approach can be applied to any species subject to the existence of appropriate anti-melanopsin antibodies.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.

ABSTRACT
Non-image related responses to light, such as the synchronization of circadian rhythms to the day/night cycle, are mediated by classical rod/cone photoreceptors and by a small subset of retinal ganglion cells that are intrinsically photosensitive, expressing the photopigment, melanopsin. This raises the possibility that the melanopsin cells may be serving as a conduit for photic information detected by the rods and/or cones. To test this idea, we developed a specific immunotoxin consisting of an anti-melanopsin antibody conjugated to the ribosome-inactivating protein, saporin. Intravitreal injection of this immunotoxin results in targeted destruction of melanopsin cells. We find that the specific loss of these cells in the adult mouse retina alters the effects of light on circadian rhythms. In particular, the photosensitivity of the circadian system is significantly attenuated. A subset of animals becomes non-responsive to the light/dark cycle, a characteristic previously observed in mice lacking rods, cones, and functional melanopsin cells. Mice lacking melanopsin cells are also unable to show light induced negative masking, a phenomenon known to be mediated by such cells, but both visual cliff and light/dark preference responses are normal. These data suggest that cells containing melanopsin do indeed function as a conduit for rod and/or cone information for certain non-image forming visual responses. Furthermore, we have developed a technique to specifically ablate melanopsin cells in the fully developed adult retina. This approach can be applied to any species subject to the existence of appropriate anti-melanopsin antibodies.

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Related in: MedlinePlus

UF008/SAP treatment has little effect on visual cliff performance.Both UF008/SAP and IgG/SAP injected groups perform quite accurately in the visual cliff test, but there is a small deficit in the UF008/SAP treated group (p<0.05, Mann-Whitney test).
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pone-0003153-g006: UF008/SAP treatment has little effect on visual cliff performance.Both UF008/SAP and IgG/SAP injected groups perform quite accurately in the visual cliff test, but there is a small deficit in the UF008/SAP treated group (p<0.05, Mann-Whitney test).

Mentions: Having revealed there are no significant morphological differences between retinas dissected from UF008/SAP injected and control eyes, we subjected mice to a visual cliff task, in order to test general visual function. Figure 6 shows that bilaterally sighted and injected mice differ slightly in their responses to a visual cliff test, but both groups perform significantly above 50% chance levels. Mice were also given a light-dark preference test that revealed no difference between UF008/SAP-injected and control mice with respect to the time spent in the dark or the number of times the mice entered the lighted chamber (65.2±3.6 vs 71.6±5.5% time in the dark and (279±53 vs 185±40 entries into the light for UF008/SAP and controls, respectively; the corresponding values for 9 blind controls were 49.7±4.3 and 316±45, both values significantly different from the other groups, p<.02). When the comparison with controls was limited to the 6 mice that were free-running under LD, there was also no difference between groups.


Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms.

Göz D, Studholme K, Lappi DA, Rollag MD, Provencio I, Morin LP - PLoS ONE (2008)

UF008/SAP treatment has little effect on visual cliff performance.Both UF008/SAP and IgG/SAP injected groups perform quite accurately in the visual cliff test, but there is a small deficit in the UF008/SAP treated group (p<0.05, Mann-Whitney test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2519834&req=5

pone-0003153-g006: UF008/SAP treatment has little effect on visual cliff performance.Both UF008/SAP and IgG/SAP injected groups perform quite accurately in the visual cliff test, but there is a small deficit in the UF008/SAP treated group (p<0.05, Mann-Whitney test).
Mentions: Having revealed there are no significant morphological differences between retinas dissected from UF008/SAP injected and control eyes, we subjected mice to a visual cliff task, in order to test general visual function. Figure 6 shows that bilaterally sighted and injected mice differ slightly in their responses to a visual cliff test, but both groups perform significantly above 50% chance levels. Mice were also given a light-dark preference test that revealed no difference between UF008/SAP-injected and control mice with respect to the time spent in the dark or the number of times the mice entered the lighted chamber (65.2±3.6 vs 71.6±5.5% time in the dark and (279±53 vs 185±40 entries into the light for UF008/SAP and controls, respectively; the corresponding values for 9 blind controls were 49.7±4.3 and 316±45, both values significantly different from the other groups, p<.02). When the comparison with controls was limited to the 6 mice that were free-running under LD, there was also no difference between groups.

Bottom Line: Intravitreal injection of this immunotoxin results in targeted destruction of melanopsin cells.In particular, the photosensitivity of the circadian system is significantly attenuated.This approach can be applied to any species subject to the existence of appropriate anti-melanopsin antibodies.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.

ABSTRACT
Non-image related responses to light, such as the synchronization of circadian rhythms to the day/night cycle, are mediated by classical rod/cone photoreceptors and by a small subset of retinal ganglion cells that are intrinsically photosensitive, expressing the photopigment, melanopsin. This raises the possibility that the melanopsin cells may be serving as a conduit for photic information detected by the rods and/or cones. To test this idea, we developed a specific immunotoxin consisting of an anti-melanopsin antibody conjugated to the ribosome-inactivating protein, saporin. Intravitreal injection of this immunotoxin results in targeted destruction of melanopsin cells. We find that the specific loss of these cells in the adult mouse retina alters the effects of light on circadian rhythms. In particular, the photosensitivity of the circadian system is significantly attenuated. A subset of animals becomes non-responsive to the light/dark cycle, a characteristic previously observed in mice lacking rods, cones, and functional melanopsin cells. Mice lacking melanopsin cells are also unable to show light induced negative masking, a phenomenon known to be mediated by such cells, but both visual cliff and light/dark preference responses are normal. These data suggest that cells containing melanopsin do indeed function as a conduit for rod and/or cone information for certain non-image forming visual responses. Furthermore, we have developed a technique to specifically ablate melanopsin cells in the fully developed adult retina. This approach can be applied to any species subject to the existence of appropriate anti-melanopsin antibodies.

Show MeSH
Related in: MedlinePlus