Retinal Ganglion Cells Functional Changes in a Mouse Model of Alzheimer’s Disease Are Linked with Neurotransmitter Alterations

2021 ◽  
pp. 1-14
Author(s):  
Joaquín Araya ◽  
Felipe Bello ◽  
Gaganashree Shivashankar ◽  
David Neira ◽  
Claudia Durán-Aniotz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Firing Rate ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Early Stage ◽  
Retinal Ganglion ◽  
Gamma Aminobutyric Acid ◽  
Functional Changes ◽  
Model Of Alzheimer’S Disease

Background: Alzheimer’s disease (AD) is the most prevalent form of dementia worldwide. This neurodegenerative syndrome affects cognition, memory, behavior, and the visual system, particularly the retina. Objective: This work aims to determine whether the 5xFAD mouse, a transgenic model of AD, displays changes in the function of retinal ganglion cells (RGCs) and if those alterations are correlated with changes in the expression of glutamate and gamma-aminobutyric acid (GABA) neurotransmitters. Methods: In young (2–3-month-old) and adult (6-7-month-old) 5xFAD and WT mice, we have studied the physiological response, firing rate, and burst of RGCs to various types of visual stimuli using a multielectrode array system. Results: The firing rate and burst response in 5xFAD RGCs showed hyperactivity at the early stage of AD in young mice, whereas hypoactivity was seen at the later stage of AD in adults. The physiological alterations observed in 5xFAD correlate well with an increase in the expression of glutamate in the ganglion cell layer in young and adults. GABA staining increased in the inner nuclear and plexiform layer, which was more pronounced in the adult than the young 5xFAD retina, altering the excitation/inhibition balance, which could explain the observed early hyperactivity and later hypoactivity in RGC physiology. Conclusion: These findings indicate functional changes may be caused by neurochemical alterations of the retina starting at an early stage of the AD disease.

Retinal ganglion cells in Alzheimer's disease and aging

2004 ◽  
Vol 33 (3) ◽  
pp. 248-257 ◽  
Author(s):  
Christine A. Curcio ◽  
David N. Drucker
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion

scholarly journals Multimodal evaluation of the melanopsin retinal ganglion cells system in relation to circadian rhythms in Alzheimer’s disease and aging

2021 ◽  
Vol 17 (S5) ◽  
Author(s):  
Chiara La Morgia ◽  
Micaela Mitolo ◽  
Aurelia Santoro ◽  
Martina Romagnoli ◽  
Michelangelo Stanzani Maserati ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythms ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion

scholarly journals Retinal ganglion cell degeneration correlates with hippocampal spine loss in experimental Alzheimer’s disease

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Ryan J. Bevan ◽  
Tim R. Hughes ◽  
Pete A. Williams ◽  
Mark A. Good ◽  
B. Paul Morgan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Dependent Manner ◽  
Retinal Ganglion ◽  
Brain Pathology ◽  
Cell Degeneration ◽  
Non Invasive

AbstractNeuronal dendritic and synaptic pruning are early features of neurodegenerative diseases, including Alzheimer’s disease. In addition to brain pathology, amyloid plaque deposition, microglial activation, and cell loss occur in the retinas of human patients and animal models of Alzheimer’s disease. Retinal ganglion cells, the output neurons of the retina, are vulnerable to damage in neurodegenerative diseases and are a potential opportunity for non-invasive clinical diagnosis and monitoring of Alzheimer’s progression. However, the extent of retinal involvement in Alzheimer’s models and how well this reflects brain pathology is unclear. Here we have quantified changes in retinal ganglion cells dendritic structure and hippocampal dendritic spines in three well-studied Alzheimer’s mouse models, Tg2576, 3xTg-AD and APPNL-G-F. Dendritic complexity of DiOlistically labelled retinal ganglion cells from retinal explants was reduced in all three models in an age-, gender-, and receptive field-dependent manner. DiOlistically labelled hippocampal slices showed spine loss in CA1 apical dendrites in all three Alzheimer’s models, mirroring the early stages of neurodegeneration as seen in the retina. Morphological classification showed that loss of thin spines predominated in all. The demonstration that retinal ganglion cells dendritic field reduction occurs in parallel with hippocampal dendritic spine loss in all three Alzheimer’s models provide compelling support for the use of retinal neurodegeneration. As retinal dendritic changes are within the optical range of current clinical imaging systems (for example optical coherence tomography), our study makes a case for imaging the retina as a non-invasive way to diagnose disease and monitor progression in Alzheimer’s disease.

Multimodal evaluation of the melanopsin retinal ganglion cells system in relation to circadian rhythms in Alzheimer's disease and aging

2021 ◽  
Vol 429 ◽  
pp. 118980
Author(s):  
Chiara La Morgia ◽  
Micaela Mitolo ◽  
Aurelia Santoro ◽  
Martina Romagnoli ◽  
Michelangelo Stanzani Maserati ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Circadian Rhythms ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion

Distinctive morphological and functional changes in retinal ganglion cells associated with normal aging and early stage of glaucoma

2016 ◽  
Vol 132 (1) ◽  
pp. 36 ◽  
Author(s):  
M. V. Zueva ◽  
M. U. Arapiev ◽  
I. V. Tsapenko ◽  
D. N. Lovpache ◽  
N. M. Maglakelidze ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Early Stage ◽  
Normal Aging ◽  
Retinal Ganglion ◽  
Functional Changes

scholarly journals FTIR imaging of the molecular burden around Aβ deposits in an early-stage 3-Tg-APP-PSP1-TAU mouse model of Alzheimer's disease

The Analyst ◽  
2017 ◽  
Vol 142 (1) ◽  
pp. 156-168 ◽  
Author(s):  
Artur Dawid Surowka ◽  
Michael Pilling ◽  
Alex Henderson ◽  
Herve Boutin ◽  
Lidan Christie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Spatial Resolution ◽  
Mouse Brain ◽  
High Spatial Resolution ◽  
Early Stage ◽  
Ftir Imaging ◽  
Model Of Alzheimer’S Disease ◽  
Tau Mouse Model

High spatial resolution FTIR imaging of early-stage 3-Tg-APP-PSP1-TAU mouse brain identifies molecular burden around Aβ deposits.

scholarly journals The involvement of gamma-aminobutyric acid in the organization of cat retinal ganglion cell receptive fields. A study with picrotoxin and bicuculline.

1976 ◽  
Vol 68 (4) ◽  
pp. 465-484 ◽  
Author(s):  
A W Kirby ◽  
C Enroth-Cugell
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Receptive Fields ◽  
Aminobutyric Acid ◽  
Retinal Ganglion ◽  
Gamma Aminobutyric Acid ◽  
Control Response ◽  
Subsequent Effect ◽  
X Cells ◽  
Y Cells

The effects of picrotoxin and bicuculline upon the discharge pattern of center-surround organized cat retinal ganglion cells of X and Y type were studied. All experiments were carried out under scotopic or possibly low mesopic conditions; mostly but not exclusively on-center cells were studied. Stimuli were chosen so that responses were either; (a) "purely" central; (b) surround dominated; or (c) clearly mixed but center dominated. In each case a pre-drug control response was estaboished, the drug was administered intravenously, and its subsequent effect upon the response was observed. In Y cells both picrotoxin and bicucullin caused the center-driven component of the response to become somewhat reduced in magnitude, while the surround component was substantially reduced. There was thus a change in center-surround balance in favor of the center-driven component. Responses of X cells remained virtually unaffected by both picrotoxin and bicuculline.

scholarly journals Cell-Subtype-Specific Remodeling of Intrinsically Photosensitive Retinal Ganglion Cells in Streptozotocin-Induced Diabetic Mice

2021 ◽  
Author(s):  
Wei-Yi Chen ◽  
Xu Han ◽  
Ling-Jie Cui ◽  
Chen-Xi Yu ◽  
Wen-Long Sheng ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Retinal Ganglion Cells ◽  
Visual Function ◽  
Functional Activity ◽  
Ganglion Cells ◽  
Early Stage ◽  
Retinal Ganglion ◽  
Diabetic Mice ◽  
Pupillary Light ◽  
Dendritic Branching

Recent evidence suggests that melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), a neuronal class regulating non-image forming (NIF) vision and generally thought to be injury-resistant, are dysfunctional in certain neurodegenerative diseases. Although disrupted NIF visual functions have been reported in patients and animals with diabetes, it remains controversial whether ipRGCs exhibit remodeling during diabetes and if so, whether such remodeling is variable among ipRGC subtypes. Here we demonstrate that survival, soma-dendritic profiles and melanopsin-based functional activity of M1 ipRGCs were unaltered in streptozotocin-induced 3-month diabetic mice. Such resistance remained at 6 months after streptozotocin administration. In contrast, M2/M3 ipRGCs underwent significant remodeling in diabetic mice, manifested by enlarged somata and increased dendritic branching complexity. Consistent with the unaltered melanopsin levels, the sensitivity of melanopsin-based activity was unchanged in surviving M2 cells, but their response gain displayed a compensatory enhancement. Meanwhile, the pupillary light reflex, a NIF visual function controlled by M2 cells, was found to be impaired in diabetic animals. The resistance of M1 cells might be attributed to the adjacency of their dendrites to capillaries, which makes them less disturbed by the impaired retinal blood supply at the early stage of diabetes.

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