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S.-K. Chen, J. L. Ecker, S. Hattar; Understanding the Complexity of ipRGCs Targeting and Functions. Invest. Ophthalmol. Vis. Sci. 2010;51(13):664.
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Intrinsically photosensitive retinal ganglion cells (ipRGCs) serve as the primary conduits for light signals originating in the outer retina to influence non-image forming functions. These inner retinal photoreceptors target the suprachiasmatic nucleus (SCN) to photoentrain circadian rhythms and the olivary pretectal nucleus (OPN) to control the pupillary light reflex (PLR). Morphological and electrophysiological studies of ipRGCs using the cre-lox system showed that ipRGCs comprise at least 4 distinct subtypes that arborize both in the ON and OFF sublamina of the inner plexiform layer (IPL). Furthermore, ipRGC subtypes have convergent but also distinct innervation patterns in the brain. Brn3b is expressed in the majority of RGCs and plays a major role in RGC differentiation and maturation. Adult brn3b knockout mice have near complete ablation of fibers innervating the OPN but have grossly normal targeting in the SCN. This indicates that a subset of ipRGCs projecting to the OPN is dependent on the Brn3b transcription factor. Therefore, we wanted to determine the complexity and targeting of the different subtypes of ipRGCs in the mammalian retina.
We use several genetic methods to label sparse populations of ipRGCs using conventional and conditional cre knock in lines that use the melanopsin promoter, in combination with Cre-dependent reporter and conditional knockout lines to decipher the complexity of the ipRGC subtypes.
We have shown that the original ipRGCs that arborize in the OFF sublamina of the IPL (known as M1) target predominantly brain regions important for non-image forming functions, whereas, non-M1 ipRGCs innervate brain regions responsible for supporting image-forming functions. In addition, we have preliminary results indicating that even the M1 ipRGCs may have distinct subpopulation that targets the OPN to influence PLR independent of circadian photoentrainment.
These results point to the possibility that distinct subtypes of ipRGCs contribute differentially to image versus non-image forming functions.
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