Navigation Links
Same cell death pathway involved in three forms of blindness, Penn team finds

Gene therapies developed by University of Pennsylvania School of Veterinary Medicine researchers have worked to correct different forms of blindness. While effective, the downside to these approaches to vision rescue is that each disease requires its own form of gene therapy to correct the particular genetic mutation involved, a time consuming and complex process.

Hoping to develop a treatment that works more broadly across diseases, a Penn Vet team used canine disease models to closely examine how retinal gene activity varied during the progression of three different forms of inherited vision disease. Their results turned up an unexpected commonality: Early on in each of the diseases, genes involved in the same specific pathway of cell death appeared to be activated. These findings point to possible interventions that could curb vision loss across a variety of inherited retinal diseases.

The work, published in PLOS ONE, was conducted by Sem Genini, a senior research investigator; William A. Beltran, assistant professor of ophthalmology; and Gustavo D. Aguirre, professor of medical genetics and ophthalmology, all of Penn Vet's Department of Clinical Studies, Philadelphia.

The team examined three forms of retinal degenerative diseases, rod cone dysplasia 1 being the most severe, or earliest onset, followed by X-linked progressive retinal atrophy 2 and then early retinal degeneration. All of these diseases involve the death of photoreceptor cells and each is caused by a distinct genetic mutation. But what scientists did not know is how the mutations trigger a molecular signaling pathway that leads to the death of photoreceptor cells.

"What we have in mind is to be able to address multiple forms of disease with one treatment," Beltran said. "We wanted to get a better understanding of whether there are any common cell death or cell survival pathways that could be targeted in some of these diseases."

The researchers 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, Beltran and Aguirre say their results suggest that these drugs or similar ones might have a role to play in the retinal diseases they investigated and perhaps in others that their team is currently studying.

"On its own," Beltran said, "a TNF-inhibitor might not be a cure, but it could be used complementary to gene therapy, either by slowing the course of degeneration before the corrective gene therapy is delivered or in combination with the corrective gene therapy."


Contact: Katherine Unger Baillie
University of Pennsylvania

Related medicine news :

1. Tripling tobacco taxes worldwide would avoid 200 million tobacco deaths
2. Jesus Was Not Born On December 25th - Controversial New Novel Tells Compelling Story About His Birth, Life and Death
3. Lung cancer death rates continue to fall, helping the decrease in overall cancer death rates
4. St. Paul Treatment Center Announces New Effort to Curb Opiate-Related Deaths in Region
5. Fosamax Lawsuits Update: Rottenstein Law Group LLP Comments on Reported $28 Million Merck ‘Jaw Death’ Settlement
6. Cigarette smoking after cancer diagnosis increases risk of death
7. New York Truck Accident Lawyer Adnan Munawar Comments on “Freak Accident” Death of 71-Year-Old NYPD Traffic Agent
8. CARING Criteria shows 1 year death risk at time of hospital admission
9. More alcohol and traffic laws mean fewer traffic deaths, NYU Steinhardt study concludes
10. Death of an adult son increases depressive symptoms in mothers, but not fathers
11. Cardiovascular Institute: Unfolded protein response contributes to sudden death in heart failure
Post Your Comments:
Related Image:
Same cell death pathway involved in three forms of blindness, Penn team finds
(Date:12/1/2015)... , ... December 01, 2015 , ... ... of Excellence (BHCOE) today announced that the organization has awarded Education and Developmental ... with a Distinguished Award. The award celebrates exceptional special needs providers that excel ...
(Date:12/1/2015)... MA (PRWEB) , ... December 01, 2015 , ... Lutronic, ... release of Clarity, the latest addition to the devices for sale in the United ... 755 nm Alexandrite and long-pulsed 1064 nm Nd:YAG lasers, into a single platform that ...
(Date:12/1/2015)... (PRWEB) , ... December 01, 2015 , ... XTC ... selected 10 semi-finalists to head to Las Vegas for CES 2016, the world’s largest ... CEO of Consumer Technology Association Gary Shapiro, Founding Partner of Pacific Investments Veronica Serra, ...
(Date:12/1/2015)... ... , ... Nurotron Biotechnology Co., Ltd., maker of cochlear implant systems, has won ... order will be from the China Disabled Persons’ Federation, a central government association, for ... for children and adults suffering from severe and profound hearing loss . The ...
(Date:12/1/2015)... IL (PRWEB) , ... December 01, 2015 , ... ... Unified Contact Center Enterprise Authorized Technology Provider (ATP) status from Cisco. This designation ... deploy and support Cisco Unified Contact Center solutions targeted to the high-end enterprise ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... December 1, 2015 --> ... research report "Nucleic Acid Labeling Market by Product (Reagents ... Random Primer, In Vitro Transcription, Reverse Transcription, End Labeling), ... MarketsandMarkets, The global market is expected to reach USD ... 2015, growing at a CAGR of 8.65%. ...
(Date:12/1/2015)... , Dec. 01, 2015 ... announced the addition of the ... Campylobacter, Cryptosporidium, E. Coli, Enterovirus, Rhinovirus, ... report to their offering. --> ... addition of the "2016 Europe ...
(Date:12/1/2015)... ANGELES , Dec. 1, 2015 CytRx ... development company specializing in oncology, today announced that it ... the company,s pivotal global Phase 3 clinical trial of ... (STS). Enrollment was originally estimated to be completed in Q1 ... being conducted under a Special Protocol Assessment from the ...
Breaking Medicine Technology: