UB vision research contributes to a rethinking of what leads to a rare, hereditary disorder causing blindness – UB Now: News and views for UB faculty…
Posted By admin on June 26, 2020
A series of papers published recently by two teams of vision researchers at UB and the University of Alabama at Birmingham (UAB) is revealing important new information about the possible cause of a condition that underlies a rare form of irreversible blindness in young children.
Retinitis pigmentosa (RP) is the label given to a family of disorders characterized by the degeneration and eventual death of the eyes photoreceptor cells, which absorb and convert light into electrical signals in the retina. Symptoms begin in childhood with night blindness and loss of peripheral vision, and the disease typically results in progressive vision loss and, ultimately, blindness.
The UB team is led by Steven J. Fliesler, SUNY Distinguished Professor and the Meyer H. Riwchun Endowed Chair Professor of Ophthalmology in the Jacobs School of Medicine and Biomedical Sciences at UB. The UAB team is led by Steven J. Pittler, professor and director of the Vision Science Research Center at the School of Optometry and Vision Science at UAB.
RP is caused by a multitude of disparate genetic mutations, Fliesler explains. However, one form known as RP59 has been classified as a congenital disorder of glycosylation (CDG). The process of glycosylation involves the addition of sugars to protein molecules to make glycoproteins, which are required for cellular development, structural integrity and viability.
But the researchers findings published this month in a paper in iScience, and two related papers published recently in the journal Cells, demonstrate that this may not be the case.
Although the more common forms of RP have been known for many decades, RP59 was only first described in 2011 in patients of Ashkenazi Jewish heritage. Those patients have a genetic defect involving mutations in the gene that encodes DHDDS, a key enzyme required for synthesizing an essential lipid-like molecule called dolichol. These patients manifest RP-like symptoms.
Up until then, Fliesler says, it was neither known nor imagined that defects in the biochemical pathway that synthesizes dolichol could cause the disorder.
In 2018, the National Eye Institute of the National Institutes of Health awarded Fliesler and Pittler a $2.2 million grant to study RP59 with the hope of eventually developing a gene therapy to treat or cure the condition.
The aim of the grant, which supports the current work, was to study the molecular mechanism underlying RP59 pathology by deleting the DHDDS gene selectively in specific cell types in the retina and examining the consequences to retinal structure and function, Fliesler explains.
The study described in the iScience paper involved targeted deletion in mouse retinal rod photoreceptor cells of the gene that encodes a critical enzyme (DHDDS) responsible for making dolichol and its derivatives, he says. Those mice exhibited a profound retinal degeneration with complete loss of rod photoreceptors by 6 postnatal weeks of age, which is among the most rapid photoreceptor degenerations ever observed.
Although we predicted the retinal degeneration, we expected that protein glycosylation in the photoreceptor cells would be severely compromised, since that process requires dolichol; yet, it was not, he says. That was a tremendous surprise.
We have not yet discovered why this happens, or what is the actual underlying mechanism of the very rapid photoreceptor degeneration observed in our novel mouse model, Fliesler says. Without knowing the underlying mechanism of RP59, it would be more difficult to develop targeted therapies to prevent, retard or cure the disease. Our results, in combination with results obtained from two other recently published studies from our group in collaboration with Dr. Pittlers lab at UAB, challenge the notion that RP59 is a congenital disorder of glycosylation.
The work is related to two previous papers, in which Fliesler and members of his UB lab are co-authors with the lead investigators at UAB. Published in Cells, the first study suggests that retinal pigment epithelium pathology may be a significant contributor to the retinal degeneration observed in humans with RP59 mutations.
More recently, the UAB and UB teams collaborated on a companion study, also reported in Cells, that showed that a knock-in mouse model (where an endogenous gene or parts of a gene have been replaced with exogenous genetic material) harboring the same mutation as found in human RP59 patients not only showed no defect in glycosylation, but failed to undergo retinal degeneration, and exhibited only very subtle physiological defects. These findings again point to a more complex mechanism for RP59 than originally thought, Fliesler notes.
Sriganesh Ramachandra Rao, formerly a graduate student in Flieslers lab at UB and now a postdoctoral researcher there, is first author on the iScience paper, as well as on the second Cells paper. Other UB authors on the paper are Lara A. Skelton, Fuguo Wu, Mark C. Butler and Xiuqian Mu. Pittler and colleagues at UAB are co-authors, along with researchers from the Polish Academy of Sciences.
The research was supported primarily by the NIH grant, with additional support from a Knights Templar Eye Foundation Career-Starter Award and a Fight for Sight Summer Student Award, as well as support from a Clinical and Translational Science Award granted to UB by the National Center for Advancing Translational Sciences of the NIH.
Fliesler conducted the research at the VA Western New York Healthcare System, where he holds a Research VA MERIT Review Award, as well as a Research Career Scientist Award, both from the U.S. Department of Veterans Affairs.
Excerpt from:
- IDF prepared to take action to stop Iran from obtaining nukes - Gantz - The Jerusalem Post - February 26th, 2021
- Israel Elections: Stop blaming Gantz, unite to fight the Right - opinion - The Jerusalem Post - February 26th, 2021
- Israel to Pay $50M to Families of Children Who Disappeared in State's Early Years - Jewish Exponent - February 26th, 2021
- Israel offers compensation to families of missing children - Minneapolis Star Tribune - February 26th, 2021
- Illinois Governor, Israeli Foreign Minister and Sheba Medical Center CEO Partner on the Chicago ARC Innovation Center to Advance Health Equity -... - February 26th, 2021
- Israel giving 'symbolic' number of COVID vaccines to Palestinians, other nations - Ynetnews - February 26th, 2021
- The dispute on how to handle Iran could cost us - JNS.org - February 26th, 2021
- Straight or natural: The best hair products for curly hair - Edmonton Journal - February 19th, 2021
- Children are increasingly the casualties of COVID - Ynetnews - February 19th, 2021
- Bidens first call in region will be Netanyahu, White House says - The Jerusalem Post - February 18th, 2021
- Veteran diplomat Gideon Meir dies at 74 - The Times of Israel - February 18th, 2021
- What I learned from starting a new job during the pandemic - CTech - February 16th, 2021
- Harris' stepdaughter accidentally highlights the complexity of Jewish identity J. - The Jewish News of Northern California - February 16th, 2021
- Lilly exec resigns after relationship that violated policy - The Republic - February 14th, 2021
- Ins and outs: Changes at Merck, Lilly and Editas - BioProcess Insider - BioProcess Insider - February 14th, 2021
- Israel not the reason Biden hasn't called Netanyahu. What is? - analysis - The Jerusalem Post - February 14th, 2021
- A place in the sun? Assessing the Turkish governments olive branch to Israel - Global Risk Insights - February 14th, 2021
- Dagashiya in decline: The slow fade of a traditional sweets institution - The Japan Times - February 7th, 2021
- This 25-year-old Ashkenazi-British-Sudanese comedian is blowing up on TikTok - Forward - February 6th, 2021
- Maxwell House Haggadah used 1695 art, calmed Ashkenazi nerves (the coffee bean is not a bean) - The Jewish Star - February 3rd, 2021
- Bahrain FM mourns victims of Holocaust in letter to Ashkenazi - The Jerusalem Post - February 3rd, 2021
- Letters to the editor - Wicked Local - February 3rd, 2021
- Verimatrix launches enhanced Application Protection service for Android - Help Net Security - Help Net Security - January 22nd, 2021
- For the first time, a Jew of color will lead pathbreaking diversity group Be'chol Lashon - Jewish Telegraphic Agency - January 22nd, 2021
- Is There a Jewish Link to Cancer? - Atlanta Jewish Times - January 18th, 2021
- Early elections increase indicators of an existential threat to Israel - Middle East Monitor - January 18th, 2021
- For the first time, a Jew of color will lead pathbreaking diversity group Be'chol Lashon - JTA News - Jewish Telegraphic Agency - January 18th, 2021
- For the first time, a Jew of color will lead Jewish diversity org Be'chol Lashon - The Jewish News of Northern California - January 18th, 2021
- Being a Black Jewish woman in America on Jan. 6 - The Jewish News of Northern California - January 18th, 2021
- New South Philly Shop Pays Homage to Traditional Jewish 'Appetizing Stores,' Features Artisanal Smoked Fish - Jewish Exponent - January 18th, 2021
- Is a Jew Allowed to Eat Synthetic Meat & Then Drink a Dairy Coffee? - Yeshiva World News - January 18th, 2021
- Beyond Chopped Liver Cookbook Gives Jewish Food a Healthy Makeover - jewishboston.com - January 18th, 2021
- Foreign Minister Gabi Ashkenazi will not run in Gantz's party - Haaretz.com - December 30th, 2020
- MK Cotler-Wunsh quits Blue and White, says shes committed to continue serving - The Times of Israel - December 30th, 2020
- TV report: Gantz, Ashkenazi considering departing politics - The Times of Israel - December 29th, 2020
- Common and rare variant prediction and penetrance of IBD in a large, multi-ethnic, health system-based biobank cohort - DocWire News - December 29th, 2020
- Thoughts on the attack on North Shore Hebrew Academys website - The Jewish Standard - December 23rd, 2020
- How can Israels left-wing parties win more Mizrahi votes? - The Jerusalem Post - December 23rd, 2020
- What will Israel's next government look like? It depends on us! - The Jerusalem Post - December 23rd, 2020
- Jon Ossoffs Letter to the Jewish Community - Atlanta Jewish Times - December 23rd, 2020
- Jews of color exist and heres why it matters - The Jerusalem Post - December 23rd, 2020
- Is Pakistan seeking to normalise ties with Israel? Here`s what new report says - Zee News - December 23rd, 2020
- 'Esau' Puts New Twist on Biblical Brotherhood - Jewish Exponent - December 23rd, 2020
- Treasures of Judaica From the Sassoon Family Collection - The Wall Street Journal - December 12th, 2020
- TV chef brings Mexican latkes and jalapeno matzah ball soup north of border - The Times of Israel - December 12th, 2020
- What are the ties that unite Spain and Israel? - opinion - The Jerusalem Post - December 12th, 2020
- Rapid and ongoing evolution of repetitive sequence structures in human centromeres - Science Advances - December 12th, 2020
- Morocco agrees to normalize ties with Israel in exchange for U.S. recognition of Western Sahara sovereignty - Haaretz - December 11th, 2020
- Ehud Olmert to 'Post': Women need to take on leadership roles in Israel - The Jerusalem Post - December 11th, 2020
- Author Joseph A. Levy's new book Forbidden Love is a moving story about love, friendship, and family for two New York professionals from different... - December 11th, 2020
- Israeli, Jordanian foreign ministers meet, with plenty of issues on their agenda - Al-Monitor - December 11th, 2020
- Ashkenazi: Netanyahu didn't mention budget once in his remarks - The Times of Israel - December 5th, 2020
- What Does the Jewish Last Name Epstein Mean? - Chabad.org - December 5th, 2020
- Films From a Vanished World - The Wall Street Journal - December 5th, 2020
- Israel and Jordan aim to thaw relations with secret meeting - Axios - December 4th, 2020
- Chanukah Foods From Around the World - Jewish Exponent - December 4th, 2020
- Bahrain minister to visit Israel, meet Netanyahu, Ashkenazi - The Times of Israel - December 4th, 2020
- Looking to the future from Izmirs glorious Jewish past - The Jerusalem Post - December 4th, 2020
- It's time to end the farce of this government - The Jerusalem Post - December 4th, 2020
- Fear of peace - Daily Pioneer - December 4th, 2020
- Becky with the good hair: Colorism and power in the Jewish community - Campus Times - November 17th, 2020
- Israel's Netanyahu Scared Fellow Countrymen Will "Misbehave" in the United Arab Emirates - Paddle Your Own Kanoo - November 17th, 2020
- Israeli FM: Biden Will Sign Amended Nuclear Deal with Iran and We Must Be Involved - The Jewish Press - JewishPress.com - November 17th, 2020
- Researchers Suggest Breast Cancer Screening in Black Women be Initiated by Age 40 - Cancer Network - November 17th, 2020
- Malawi to be first African nation to open embassy in Jerusalem - Cleveland Jewish News - November 5th, 2020
- Malawi to be first African state with embassy in Jerusalem - The Jerusalem Post - November 5th, 2020
- Will a possible Biden win have an influence on EU-Israel relations ? - European Jewish Press - November 5th, 2020
- Great non-fiction on tap at upcoming Arts, Books & Culture Festival - Jewish Community Voice - November 5th, 2020
- Rabbis volunteering in Philadelphia encounter the unexpected: Peace and optimism - The Times of Israel - November 5th, 2020
- Comprehensive Genomic Analysis in Some Patients With Breast Cancer Reveals Rare, Pathogenic TP53 Variant in Families of Ashkenazi Jewish Descent -... - October 25th, 2020
- Spiced, stuffed, and skinless Jewish sausages - The Jewish Star - October 25th, 2020
- Jewish Organization Sharsheret Helps Women with Breast and Ovarian Cancer During Pandemic - Jewish Journal - October 25th, 2020
- Why Israel's anti-Netanyahu protests will not change the system - Middle East Eye - October 25th, 2020
- Cleopatra's Golden Rule - or, she who has the gold, makes the rules - Neos Kosmos - October 20th, 2020
- Maybe its true Israels Jews are incapable of sovereignty - Haaretz.com - October 20th, 2020
- In an Ashkenazi world, I'm struggling to connect to my Bukharian heritage - Cleveland Jewish News - October 18th, 2020
- Shtetl-inspired sweatshirts are creating controversy online but is shtreetwear really beyond the pale? - Forward - October 18th, 2020
- Redefining the Diaspora: The Jews of Latin America and Beyond - jewishboston.com - October 18th, 2020
- Vegetarian cholent and kishke with a side of Shabbat mysticism J. - The Jewish News of Northern California - October 18th, 2020
- Talking to Your Kids About Breast Cancer - Dan's Papers - October 18th, 2020
Comments