Chromatic Pupillometry Findings in Alzheimer's Disease. Romagnoli Martina,Stanzani Maserati Michelangelo,De Matteis Maddalena,Capellari Sabina,Carbonelli Michele,Amore Giulia,Cantalupo Gaetano,Zenesini Corrado,Liguori Rocco,Sadun Alfredo A,Carelli Valerio,Park Jason C,La Morgia Chiara Frontiers in neuroscience 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. 10.3389/fnins.2020.00780

Nonamyloidogenic processing of amyloid beta precursor protein is associated with retinal function improvement in aging male APP/PS1ΔE9 mice. Joly Sandrine,Lamoureux Simon,Pernet Vincent Neurobiology of aging Vision declines during normal aging and in Alzheimer's disease (AD). Although the toxic role of amyloid beta (Aβ) has been established in AD pathogenesis, its influence on the aging retina is unclear. Using APP/PS1ΔE9 transgenic (TG) mice, a classical AD model, the retinal cell function and survival was assessed by electroretinogram (ERG) recordings and immunofluorescent stainings. Strikingly, photopic ERG measurements revealed that the retinal response mediated by cones was preserved in aging TG mice relative to WT controls. In contrast to the cortex, the expression of mutated APP and PS1ΔE9 did not allow to detect Aβ or amyloid plaques in 13-month-old male TG retinae. In addition, the CTFβ/CTFα ratio was significantly lower in retinal samples than that in cortical extracts, suggesting that the nonamyloidogenic pathway may endogenously limit Aβ formation in the retina of male mice. Collectively, our data suggest that retinal-specific processing of amyloid may confer protection against AD and selectively preserve cone-dependent vision during aging. 10.1016/j.neurobiolaging.2017.02.004

Identification of early-onset photoreceptor degeneration in transgenic mouse models of Alzheimer's disease. Zhang Jie,Gao Feng,Ma Yuqian,Xue Tian,Shen Yong iScience Light sensitivity of the vertebrate retina relies on the integrity of photoreceptors, including rods and cones. Research in patients with Alzheimer's disease (AD) and in AD transgenic mice reports that accumulated amyloid-β (Aβ) plaques in the retina are toxic to retinal neurons. Moreover, Aβ plaques are deposited around the rods and cones, yet photoreceptor anomalies remain unclear in AD. Here, we identify the progressive degeneration of rods and cones characterized by impaired expression of phototransduction proteins, morphological alterations, functional deficits, and even cell loss. Furthermore, we demonstrate that cell senescence and necroptosis were involved in rod degeneration. Importantly, using in vivo scotopic electroretinogram, we detected rod degeneration in early-stage AD transgenic mice before Aβ plaques were observed in the brain. Moreover, we demonstrate that rod degeneration was among the earliest AD retinal manifestations compared with other types of retinal neurons. Overall, our study is the first to identify and detect in vivo, early-onset photoreceptor degeneration in AD. 10.1016/j.isci.2021.103327