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A. Engelund, J. Hannibal, J. Fahrenkrug; Pituitary Adenylate Cyclase Activating Peptide (PACAP) Signalling in the Pupillary Light Response. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2560.
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Intrinsically photosensitive retinal ganglion cells (ipRGCs), which project to areas in the mammalian brain involved in non image forming photoperception, are involved in light entrainment of the circadian clock, masking behaviour in rodents, modulation of melatonin secretion, and regulation of the pupillary light reflex (PLR). In the rat, we have previously demonstrated that the neuropeptide PACAP (pituitary adenylate cyclase activating peptide) is co-stored with melanopsin in ipRGCs and that PACAP containing retinal axons project to the olivary pretectal nucleus (OPN) involved in PLR. Furthermore, we have shown that the specific PACAP receptor (PAC1-R) is found in the rat OPN. In the present study we examined the role of PACAP signalling in the PLR using mice lacking the PAC1-R.
To verify the presence of PACAP in retinal projections in the OPN in mice, we performed bilateral tracing by intravitreal injections of Choleratoxin Subunit B (CtB) followed by perfusion fixation. CtB and PACAP was visualized by immunohistochemistry. Expression of PAC1-R in the OPN was identified by in situ hybridization. The PLR was studied in PAC1-R KO mice and wild type littermates. Unanaesthetized dark-adapted mice were hand restrained and exposed to white halogen light (30µW/cm2) into one eye for 2 minutes, and the pupil size was recorded in the same eye.
Co-Localization of PACAP and CtB immunoreactivity was observed in the rostral, medial and dorsal parts of the OPN confirming the innervation of the OPN by PACAP containing retinal fibres. Expression of the PAC1-R was visualized in the mouse OPN. Upon light stimulation PAC1-R KO mice and wild type animals showed maximal pupillary constriction 15 seconds after lights on with similar constriction patterns. When exposed to continuous light for 2 min, the PAC1-R KO mice failed to sustain the constriction. A slow pupillary dilation (escape) was detected in KO mice after 45 seconds and lasting throughout the light stimulation.
PACAP mediated signalling via the PAC1-R seems to play a role in the pupillary reflex mediated via ipRGCs of the mouse.
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