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Editors Selection IGR 15-4

IOP-Related: Melanopsis containing RGC and circadian rhythm

Comment by John Liu on:

23051 Glaucoma alters the circadian timing system, Drouyer E; Dkhissi-Benyahya O; Chiquet C et al., PLoS ONE, 2008; 3: e3931

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For a complicated biological system like the human body, a synchronized master circadian (24-hour) clock in the brain with the environment is critically important in everyday life. When patients with abnormal circadian rhythms, such as sleep disorder, are presented with different degrees of blindness, their symptoms are attributed to a lack of light input to adjust biological rhythms and not a damage to the master circadian clock. Is it possible that a selective loss of retinal ganglion cells in the case of glaucoma can lead to disturbance of the circadian timing system in addition to the deficits in visual function? We might have a lead. Several years ago, a specialized subset of retinal ganglion cells (less than 1%) expressing a new photopigment of melanopsin was discovered in rodents. These retinal ganglion cells provide photic input to the master circadian clock in the suprachiasmatic nucleus. Using a rat model of laser-induced high intraocular pressure and glaucomatous pathology, Drouyer et al. (486) demonstrated that these melanopsin-containing retinal ganglion cells were equally susceptible to an elevated intraocular pressure as other retinal ganglion cells. There were 50-70% reductions in the nerve terminals of retinal ganglion cells to both the visual and non-visual brain structures including the suprachiasmatic nucleus. The affected rats with bilateral loss of retinal ganglion cells responded slower and more inconsistently to the shifting of environmental light-dark cycle than the rats with healthy eyes. These elaborate experiments suggest that human glaucoma patients with severe bilateral loss of retinal ganglion cells have the potential to suffer circadian rhythm disturbances in addition to visual impairments.

Human glaucoma patients with severe bilateral loss of retinal ganglion cells have the potential to suffer circadian rhythm disturbances

Fortunately, environmental light is not the only stimulus, more often called 'zeitgeber', used by mammals to adjust their master circadian clocks. In nature, other environmental factors including temperature, food availability, humidity, and even social contact could all act to adjust the master circadian clock. When the dominant zeitgeber of light is under stress, likely in the case of advanced glaucoma, other second-line zeitgebers may be called into action. Already, some advanced glaucoma patients may have unknowingly employed these alternative mechanisms to avoid the adverse effects associated with circadian rhythm malfunctions due to the loss of retinal ganglion cells. For patients who suffer severe jetlag or seasonal affective disorder, it is known that simple behavior changes may help in resetting the right biological rhythms. For example, frequent gatherings in outdoor cafes with friends are better than having late evening meals alone under dim lights. Similar strategies may work for those advanced glaucoma patients who have not sought every possible way to improve their quality of life. While the loss of visual function is irreversible in these glaucoma patients, any suffering associated with circadian rhythm malfunction is unnecessary and can be reversed. The best news for our patients is that more information is on the way. With the recent discovery of this new photopigment in the retinal ganglion cells, new research is offering hope that circadian rhythm malfunctions related to glaucoma can be diagnosed and treated effectively.

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