Abstract
Purpose :
Glaucoma is the second major cause of blindness worldwide and is characterized by the loss of the retinal ganglion cells (RGC) which convey visual information from the retina to the brain. More than 40 subtypes of RGCs have been identified and studies suggest that their susceptibility to insults differ. In particular, one type of retinal ganglion cells, intrinsically photosensitive retinal ganglion cells (ipRGC), has been shown to be relatively resistant to damage in glaucoma and similar injuries. ipRGCs consist of 6 subtypes, M1-M6, each one projecting to different brain areas and involved in distinct functions such as circadian entrainment, the pupillary light reflex, image forming vision, etc. Accordingly, it is important to determine the correlation between the loss of particular ipRGCs subtypes and behavioral deficits such as circadian dysfunction and vision loss. Such information will provide important insights to address the pathologies of glaucoma patients.
Methods :
In this study, we used laser photocoagulation of the trabecular meshwork of the eyes to induce chronic ocular hypertension (OHT). Visual acuity and contrast sensitivity of the animals were measured by the optomotor test. We also assessed circadian rhythmicity and photoentrainment in these mice through the progression of the disease. Finally, retinas were dissected, immunostained for RGC subtypes, and flatmounted for confocal imaging. We quantified the survival of RGCs and ipRGC subtypes in mice with chronic OHT.
Results :
We found that ipRGCs are more resistant to the ocular hypertension insult than the general RGC population. Moreover, the survival of ipRGCs depends on subtypes. Specifically, M1 and M2 cells survived better than M4s. Though the contrast sensitivity and visual acuity of the OHT group dropped significantly, circadian rhythmicity and photoentrainment were barely disrupted.
Conclusions :
Our results suggest the circadian behaviors were relatively well maintained with glaucoma progression, which is correlated with the survival of ipRGCs . Future studies are needed to dissect out the neural circuit and its underlying mechanisms.
This is a 2021 ARVO Annual Meeting abstract.