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J. Ecker, A. Guler, R. J. Lucas, S. Hattar; Genetic Ablation of Melanopsin-Containing Retinal Ganglion Cells Severely Attenuates Light-Dependent Physiological Functions. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2989.
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In the absence of functional rod and cone photoreceptors, mammals retain the ability to detect light for a variety of physiological functions such as circadian photoentrainment, pupillary light reflex, and direct effects of light on behavior (masking). This is attributed to a class of retinal ganglion cells that are intrinsically photosensitive (ipRGCs) and express the photopigment melanopsin. It was previously demonstrated that loss of melanopsin results in attenuated pupil constriction, phase shifting, and negative masking. In addition, triple knockout mice in which the phototransduction pathways of rods, cones, and ipRGCs are disabled fail to detect light for any of the aforementioned functions, and are therefore blind for both image and non-image forming visual functions.The newly identified ipRGCs are ganglion cells; like other RGCs, they receive rod and cone input and relay it to the brain. As such, these cells signal light both intrinsically using the melanopsin photopigment and extrinsically through input from rods and cones. The present research aimed to determine the role of each of these mechanisms in mediating non-image-forming functions.
We have generated mice expressing the diphtheria toxin A subunit (DTA) under the control of the melanopsin promoter to genetically ablate the ipRGCs. Using anterograde cholera toxin tracings and X-gal staining, we determined the projections of the total population of RGCs and those of the ipRGCs in the DTA animals. Using pupil constriction and wheel running activity rhythms, we investigated the light sensitivity of the DTA animals.
We determined that DTA mice are severely impaired in photoentrainment, pupil constriction, and negative masking responses. These defects are much more severe in the DTA animals compared to melanopsin knockout mice, suggesting that rods and cones signal nearly exclusively through ipRGCs for these non-image light-dependent functions. Both anatomically and physiologically, we have shown that the defects in the DTA animals are confined to non-image but not image-forming visual functions.
Our results strongly indicate that rods and cones compensate for the absence of the intrinsic photosensitivity of ipRGCs by signaling exclusively through melanopsin containing retinal ganglion cells. This shows that the melanopsin system, acting as photoreceptors and ganglion cells, plays the predominant role in signaling light information for non-image-forming functions.
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