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Same cell death pathway involved in three forms of blindness, Penn team finds
Date:1/16/2014

chers looked at the activity of 112 genes in diseased retinas and compared it to gene activity in normal retinas. They assessed gene activity at time points known to correspond with key phases of disease: the "induction phase," the time before the peak level of photoreceptor cell death; the "execution phase," when the highest rates of photoreceptor cell death occur; and the "chronic phase," during which photoreceptor cell death continues at somewhat reduced levels.

During the execution and chronic phases of disease, the researchers identified a number of genes involved in programmed cell death, or apoptosis, that had noticeably different patterns of expression between the diseased and normal dogs.

Of note, several proteins involved in the tumor necrosis factor, or TNF, pathway increased in activity during the induction and execution phases. This pathway is implicated in many diseases, from diabetes to cancer to rheumatoid arthritis.

"This is quite a new result," Genini said. "It was not expected to have the TNF pathway upregulated."

"We assumed," Aguirre said, "the diseases would be different from one another and that cells would commit suicide by their own specific pathway and that perhaps quite late they would have a common final pathway. But what this shows is that there is an early trigger that is quite similar among all three diseases."

An additional surprise was that the differentially expressed proteins were present not only in photoreceptor cells but also in other cells in the retina, including horizontal and Mller cells.

"We were focusing on what would happen with the photoreceptor cells, the cells that we knew were dying," Beltran said. "But what our results are telling us is that, sure, they are dying, but there is something else happening with the cells that they talk to."

Pharmaceutical companies have already developed TNF-inhibitors to treat diseases like rheumatoid arthritis. Genini, Be
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Contact: Katherine Unger Baillie
kbaillie@upenn.edu
215-898-9194
University of Pennsylvania
Source:Eurekalert  

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