Retinal Ganglion Cells and Circadian Rhythms in Alzheimer’s Disease, Parkinson’s Disease, and Beyond

Abstract

There is increasing awareness on the role played by circadian rhythm abnormalities in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The characterization of the circadian dysfunction parallels the mounting evidence that the hallmarks of neurodegeneration also affect the retina and frequently lead to loss of retinal ganglion cells (RGCs) and to different degrees of optic neuropathy. In the RGC population, there is the subgroup of cells intrinsically photosensitive and expressing the photopigment melanopsin [melanopsin-containing retinal ganglion cells (mRGCs)], which are now well known to drive the entrainment of circadian rhythms to the light–dark cycles. Thus, the correlation between the pathological changes affecting the retina and mRGCs with the circadian imbalance in these neurodegenerative diseases is now clearly emerging, pointing to the possibility that these patients might be amenable to and benefit from light therapy. Currently, this connection is better established for AD and PD, but the same scenario may apply to other neurodegenerative disorders, such as Huntington’s disease. This review highlights similarities and differences in the retinal/circadian rhythm axis in these neurodegenerative diseases posing a working frame for future studies.

Phosphorylated α‐synuclein in the retina is a biomarker of Parkinson's disease pathology severity

“…Despite these differences between studies, further investigations of the eye in PD are desirable, given that it is known that ocular structures are involved in the pathology of several neurodegenerative diseases. 33,47 For example, tears, 48,49 lens, 50,51 cornea, 52 and retina 53 have already been investigated and proposed as sources for possible PD biomarkers.…”

24-h Activity Rhythms and Health in Older Adults

“…Patients have a higher fragmentation, lower stability, lower amplitude, and lower mesor than healthy controls [40][41][42]. A low stability is also associated with poorer cognitive performance in Parkinson's disease [42].…”

Oculo‐visual abnormalities in Parkinson's disease: Possible value as biomarkers

“…) as well as other sensory systems and motor function . In addition, sleep and circadian disturbances are a frequent complaint of PD patients associated with the eye, in particular the melanopsin‐containing RGCs, which are believed to control the circadian rhythm . In conclusion, visual complaints are common in PD patients, are likely to originate from a combination of retinal and (sub)cortical disease manifestations, and often affect activities of daily living (Table ).…”

“…Delayed VEPs were demonstrated to correlate with severity of motor symptoms and disease duration, 33,126 whereas pattern ERG abnormalities correlated with clinical stage and disease duration and predicted reduced quality of life. 36,98,125 This led Garcia-Martin and colleagues 33 to conclude that pattern ERG may be used for detecting patients with a higher risk of progression. In addition, they and others have concluded that combining OCT and ERG/VEP biomarkers could increase diagnostic power and aid prediction of quality of life and disease severity.…”