Melanopsin Expressing Retinal Ganglion Cells and Neurodegenerative Disease

Submitted by palmergrabner on Fri, 02/03/2023 - 12:54

There are many different cells involved in the pathway that communicates the light detected by photosensors in the retina to the rest of the brain. One important group of cells sense light, but do not help us see: they are involved in other functions such as maintaining/resetting the circadian rhythm. This particular group of cells are known as melanopsin-expressing retinal ganglion cells (mRGC). 


The circadian rhythm, otherwise known as the sleep-wake rhythm, is an important internal clock in the body. It helps regulate certain hormone levels in the body, particular melatonin, which influences sleep. This cycle's balance is essential for both our physical and mental well being. mRGCs help regulate this rhythm by sensing high frequency waves of light, mainly blue light that excites their photopigment. The main source of blue light for these cells is the sun. In recent years, there have been concerns that blue light from electronics could contribute to the excitation of these cells' photopigment and cause issues. Instead of projecting to the thalamus like a majority of cells in the retina, mRGCs synapse to many peculiar places. When mRGCs project to the hypothalamus, these cells synapse onto the master circadian pacemaker. These cells can also project to the olivary pretectal nucleus, where they play a role in the pupillary light reflex (figure 1). 

Figure 1: The pupillary light reflex. 

With normal aging, mRGC concentration and densities do not change. In other words, mRGCs are relatively stable due to their importance in regulating circadian rhythm. However, some neurodegenerative diseases, such as Alzheimer's disease and Parkinson’s disease, have shown to heavily affect these cells. It is not surprising then, that both AD and PD have symptoms of circadian rhythm disturbance. In AD, amyloid plaques are found in the retina. These plaques interfere with cells and are thought to be the result of AD. A research group in Italy found that these plaques tend to congregate around mRGCs. This disruption of mRGCs could be responsible for the sleep disorders found in patients with Alzheimers. Similar deposits, called alpha synucleins, are found surrounding the mRGCs in Parkinson’s. 

Figure 2: This image shows Alzheimer's patients on the left and Parkinson’s on the right. On the left, there is a loss of axons resulting in axonal thinning. In the right, there is a depletion of axons in the lower parts of the optic nerve. 

Furthermore, certain time based behavioral or physiological patterns are found in both diseases. For example, patients with AD might sundown, which can result in aggressive or agitated behavior after the sun has set. Patients with AD also have shorter periods of REM wave sleep. Patients with Parkinson’s have a variety of rhythms messed up: their blood pressure, gene expression, melatonin rhythm, and many others appear to function abnormally. Thus, understanding the role of mRGCs is important in helping to alleviate many of the major behavioral and physiological issues associated with these neurodegenerative diseases. 


Overall, mRGCs play a critical role in maintaining our circadian rhythm, which in turn influences our mood and other physiological processes. Further understanding these relatively new cells can provide insight into the mechanisms of specific neurodegenerative diseases such as Alzheimers and Parkinson’s.