Abstract
Intrinsically photosensitive melanopsin retinal ganglion cells (mRGCs) are crucial for non-image forming functions of the eye, including the photoentrainment of circadian rhythms and the regulation of the pupillary light reflex (PLR). Chromatic pupillometry, using light stimuli at different wavelengths, makes possible the isolation of the contribution of rods, cones, and mRGCs to the PLR. In particular, post-illumination pupil response (PIPR) is the most reliable pupil metric of mRGC function. We have previously described, in post-mortem investigations of AD retinas, a loss of mRGCs, and in the remaining mRGCs, we demonstrated extensive morphological abnormalities. We noted dendrite varicosities, patchy distribution of melanopsin, and reduced dendrite arborization. In this study, we evaluated, with chromatic pupillometry, the PLR in a cohort of mild-moderate AD patients compared to controls. AD and controls also underwent an extensive ophthalmological evaluation. In our AD cohort, PIPR did not significantly differ from controls, even though we observed a higher variability in the AD group and 5/26 showed PIPR values outside the 2 SD from the control mean values. Moreover, we found a significant difference between AD and controls in terms of rod-mediated transient PLR amplitude. These results suggest that in the early stage of AD there are PLR abnormalities that may reflect a pathology affecting mRGC dendrites before involving the mRGC cell body. Further studies, including AD cases with more severe and longer disease duration, are needed to further explore this hypothesis.
Highlights
Melanopsin retinal ganglion cells are intrinsically photosensitive RGCs because of the expression of the photopigment melanopsin (Berson et al, 2002; Hannibal et al, 2002; Hattar et al, 2002)
We evaluated for the first time, using chromatic pupillometry, aimed at isolating the Melanopsin retinal ganglion cells (mRGCs) contribution (Park et al, 2017), the pupillary light reflex (PLR) in a cohort of 26 definite mild-moderate Alzheimer’s disease (AD) patients compared to a group of age- and gender-matched controls
The post-illumination pupil response (PIPR), which is the most reliable marker of mRGC-mediated PLR, was not significantly different between AD and controls, but we found a significant difference in terms of transient PLR amplitude between AD and controls under dark-adaption
Summary
Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive RGCs because of the expression of the photopigment melanopsin (Berson et al, 2002; Hannibal et al, 2002; Hattar et al, 2002). These cells contribute to non-image forming functions of the eye including circadian photoentrainment [projecting via the retino-hypothalamic tract (RHT) to the suprachiasmatic nucleus (SCN) of the hypothalamus] and regulation of the pupillary light reflex (PLR) [via projections to the olivary pretectal nucleus (OPN)] (Sadun et al, 1984; Hannibal et al, 2004, 2014; Baver et al, 2008; Chen et al, 2011; Li and Schmidt, 2018). Extensive morphological abnormalities with dendrite varicosities, patchy distribution of melanopsin, and reduced dendrite arborization were noted in remaining mRGCs of AD retinas (La Morgia et al, 2016)
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