Matthew Campbell, PhD Smurfit Institute of Genetics Trinity College Dublin Dublin

Circadian Rhythm of Retinal Eye Vessels May Influence Age Related Macular Degeneration Interview with:

Matthew Campbell, PhD Smurfit Institute of Genetics Trinity College Dublin Dublin

Dr. Campbell

Matthew Campbell, PhD
Smurfit Institute of Genetics
Trinity College Dublin
Dublin What is the background for this study? What are the main findings?

Response: Age related macular degeneration (AMD) is the most common form of central retinal blindness in the world. However the underlying causes and initiating factors for disease progression are still not clear. It is classically a disease of the outer retina, where cells called retinal pigment epithelial (RPE) cells degenerate. However, our findings suggest that some of the early initiating events that promote AMD progression are actually coming from the inner retina and more specifically the microvasculature of the inner retina.

We discovered that a gene called claudin-5 appears to be regulated by a circadian rhythm that in turn can regulate what gets into and out of the retina on a daily basis. Dysregulating the levels of this component made the inner retinal blood vessels marginally leaky and promoted a pathology that was AMD-like in animal models.  We also showed that the blood vessels of the retina appear to be highly dynamic in human subjects and can appear leakier at different times of the day, likely a mechanism that allows for clearance and replenishment of material into and out of the retina.  It is this process we believe breaks down in early AMD. What should readers take away from your report? 

Response: This is the first report that the blood vessels of the inner retina may be involved in the very early stages of AMD.  If we can understand these processes in more detail, we may be able to tailor treatments to prevent the progression of dry AMD to its end stage termed Geographic atrophy. What recommendations do you have for future research as a result of this work?

Response: We are now in the process of examining the integrity of the retinal blood vessels in all stages of AMD, early, moderate and late stage so that we can fully understand at what stage we could therapeutically intervene.  Added to this, future research efforts should be focused at regulating the integrity of he so-called inner blood retina barrier which may aid in the prevention of AMD progression. 

Any disclosures? Trinity College Dublin owns an IP portfolio related to regulating the retinal blood vessels to treat AMD. 


Dysregulated claudin-5 cycling in the inner retina causes retinal pigment epithelial cell atrophy

Natalie Hudson, … , Sarah L. Doyle, Matthew Campbell

Published August 8, 2019 
Citation Information: JCI Insight. 2019;4(15):e130273. 

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Last Updated on August 8, 2019 by Marie Benz MD FAAD