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Shih-Kuo Chen, Melissa Simmonds, Tudor Badea, Samer Hattar; Brn3b Expression Defines Functional Specialization Of Melanopsin-expressing Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5284.
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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). Recent studies indicate that ipRGCs can be classified into at least 5 different subtypes according to defined morphological and electrophysiological parameters. We aimed to determine whether these different subtypes could be differentiated molecularly. To achieve this, we studied a transcription factor, Brn3b, which belongs to the Brn3 transcriptional factor family that are expressed in the majority of RGCs and contribute to RGC differentiation and maturation.
We used immuncytochemistry to determine which ipRGCs express Brn3b. We also used genetic methods to generate mice that either label or ablate Brn3b positive ipRGCs. We measured circadian photo-entrainment, visual and pupillary light reflex behaviors to determine the physiological outcomes of specifically ablating Brn3b positive ipRGCs.
Here we show that ipRGCs are comprised of distinct subpopulations that differentially express the Brn3b transcription factor and can be functionally distinguished. Brn3b-negative ipRGCs innervate the suprachiasmatic nucleus (SCN) of the hypothalamus, whereas Brn3b positive ipRGCs innervate all other known brain targets, including the olivary pretectal nucleus. Consistent with these innervation patterns, selective ablation of Brn3b positive ipRGCs does not impair circadian photoentrainment, but eliminates pupillary light reflex responses.
We have shown that circadian photoentrainment and pupillary light reflex are regulated by distinct group of ipRGCs based on the expression pattern of the transcription factor Brn3b. These studies raise the intriguing possibility that these distinct ipRGCs utilize separate development programs to target the SCN versus the OPN.
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