65 — Retinal Ganglion Cells and Circadian Rhythms in Alzheimer's Disease, Parkinson's Disease, and Beyond

My mother recently mentioned that she had started learning about light therapy as a proxy for gamma-wave “recalibration” in Alzheimer’s patients: Radiolab covered gamma-wave mouse light therapy in a 2016 episode, and more recently the idea has been gaining traction in human therapies.

Gamma waves — somewhere around 40Hz — are the subject of a lot of science, and a lot of bogus pseudoscience… Even the official Wikipedia page on gamma waves contains this garbage phrase:

According to a popular theory, gamma waves may be implicated in creating the unity of conscious perception (the binding problem).

Gag me with a tetrode.

But there has been reputable research on the role of light in brain disorders as well; considering the huge amount of the human brain that is dedicated to vision, it’s intuitive that light affects the brain in a significant way.

I’ve added a few papers on this subject to my #365papers foray; hopefully they’ll shed some light thoughts on the matter.

Specialized retinal ganglion cells, such as melanopsin-containing RGCs (mRGCs) or intrinsically photoreceptive RGCs (ipRGCs) transmit signals to brain areas known to control circadian rhythms (namely, the suphrachiasmatic nucleus, or SCN). Optical coherence tomography (OCT) has shown that neurodegeneration in Alzheimer’s and Parkinson’s diseases extends into the retina (which we could have guessed, given the retina’s degenerative qualities in multiple sclerosis).

mRGCs in particular — of all of the many types of retinal ganglion cells — are preferentially lost in Alzheimer’s retinas; AD patients often have a difficult time retaining normal sleep schedules. 80% of Parkinson’s patients report sleep disturbances as well, though PD patients’ parvocellular RGCs are generally most affected (mRGCs on the other hand are magnocellular).

That these RGCs are often found depleted or dead in AD/PD retina, surrounded by Aβ or α-synuclein, is a very strong indicator that these neurodegenerative diseases are quite present in the retina, and the variance of circadian rhythms in AD/PD brains may be a result of this.