News Releases

November 29, 2018
Media Contact: Leigh DeLozier, 404-778-3711

P. Michael Iuvone, PhD., director, Vision Research, with his research core team
P. Michael Iuvone, PhD., director, Vision Research, with his research core team

Emory Eye Center and Morehouse School of Medicine researchers share new discovery connecting retinal development and photoreceptor viability during aging to circadian rhythm

(Atlanta) – New findings published by P. Michael Iuvone, PhD, director of vision research at Emory Eye Center, and others at Emory and Morehouse School of Medicine show that circadian clock dysfunction can contribute to abnormal visual function during development and aging.

Their research, “Removal of clock gene Bmal1 from the retina affects retinal development and accelerates cone photoreceptor degeneration during aging” was published by Proceedings of the National Academy of Sciences USA on Nov. 29, 2018. The work was a collaboration between Emory Eye Center scientists and the lab of Gianluca Tosini, PhD, at Morehouse School of Medicine.

Mammalian retinas contain an autonomous circadian clock system that controls many physiological functions within that tissue. In this study, the teams investigated how removing a specific “clock gene,” Bmal1, affected visual function, retinal circuitry, and photoreceptor viability in both young and old mice.

Previous studies have shown that the retinal clock and its circadian outputs play an important role in the regulation of retinal functions. Iuvone and Tosini’s team extended these findings by examining the effects of Bmal1 disruption on retinal function in relation to age.

“Accumulating evidence indicates that disruption of circadian rhythms contributes to the development of many diseases,” Iuvone says. “We demonstrated that removing the Bmal1 gene from the retina has multiple effects on rod and cone signaling pathways.”

For example, Bmal1 removal significantly affects visual information processing and reduces the thickness of inner retinal layers. The absence of Bmal1 also affected visual acuity and contrast sensitivity. Another important finding was a significant age-related decrease in the number of cone photoreceptors (outer segments and nuclei) in mice lacking Bmal1, which suggests that these cells are directly affected by Bmal1 removal.

“When we genetically disrupted the circadian clocks in the retinas of mice, we found accelerated age-related cone photoreceptor death, similar to that in age-related macular degeneration in humans,” Iuvone says. “This loss of photoreceptor cones affects retinal responses to bright light.

“We also noted developmental effects in young mice,” Iuvone continues, “including abnormalities in rod bipolar cells that affected dim light responses. These findings have potential implications for pregnant shift workers and other women with sleep and circadian disorders, whose offspring might develop visual problems due to their mother’s circadian disruption.”

As part of their work, the team is the first to report the observation that retinal Bmal1 removal caused stunting of rod bipolar cell dendrites and thinning of the retina’s OPL (outer plexiform layer) in both young and old mice. This could indicate that Bmal1 must be present in rod bipolar cells in order to develop normally and promote synapses growth between the OPL and rods and cones.

Iuvone is the Sylvia Montag Ferst and Frank W. Ferst Professor of Ophthalmology in the Emory University School of Medicine. He became director of research at the Emory Eye Center in September 2009. Iuvone is a leader in numerous research organizations, including the Association for Research in Vision and Ophthalmology (ARVO) and the International Society of Eye Research. He serves as principal investigator for National Eye Institute and Department of Defense grants that study retinal function, circadian rhythms, and therapies for ocular and brain trauma that affect vision.

Tosini is Chief Scientific Research Officer at Morehouse School of Medicine and also serves as chair and professor of the Morehouse Department of Pharmacology and Toxicology. He is an adjunct professor of ophthalmology at Emory University School of Medicine.

Iuvone and Tosini have worked on research together for more than 20 years; they began working on this project in 2014. Their next focus will be on trying to understand the mechanisms and possible treatments to prevent vision problems associated with circadian disruption.

The research was funded by the National Eye Institute, Research to Prevent Blindness, Inc., and the Abraham J. and Phyllis Katz Foundation.

 


About Emory Eye Center’s Research Program

From its inception in 1964, Emory Eye Center’s scientific research laboratory has been home to award-winning scientists who dedicate their lives to understanding catastrophic eye diseases that affect people worldwide. Their scientific discoveries have significantly contributed to treatments for patients with conditions such as eye cancer, hereditary cataracts, diabetic retinopathy, age-related macular degeneration, idiopathic intracranial hypertension, and more.  

 

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