Sony Pixel Power calrec Sony

March 22, 2021

23/03/2021

New genetic links found to rare eye disease, opening the door to better diagnostics and potential treatments The gene mutations explain why patients with MacTel are unable to produce enough of an amino acid needed for eye health.

March 22, 2021

LA JOLLA, CA An analysis of thousands of genomes from people with and without the rare eye disease known as MacTel has turned up more than a dozen gene variants that are likely causing the condition to develop and worsen for a significant share of patients.

The discovery, by a team of scientists from Scripps Research and the Lowy Medical Research Institute, in collaboration with Columbia University in New York and UC San Diego, provides a new avenue to pursue for diagnosis and treatment. It also sheds light on fundamental aspects of metabolism in the retina, a tissue with one of the highest energy demands in the human body. Findings appear today in the journal Nature Metabolism.

It's exciting to uncover new answers to the many questions surrounding this rare and complex eye disease, says Martin Friedlander, MD, PhD, professor at Scripps Research and president of the Lowy Medical Research Institute in La Jolla. Although we've known that MacTel has a genetic component, the precise variants had remained elusive. These findings will serve as a springboard for further scientific investigation and as a guide to potential therapeutic targets.

MacTel, short for macular telangiectasia type 2, is a progressive and debilitating eye disease that occurs in roughly one out of 5,000 people, or about 2 million people worldwide. A disease of the retina, the light-sensing tissue at the back of the eye, MacTel causes a gradual deterioration of central vision, interfering with critical tasks such as reading and driving.

Piecing together the puzzle

For more than 15 years, scientists have collaborated in an international effort, the MacTel Project, to find the cause of MacTel and develop treatments. Earlier studies found patients had low levels of an amino acid called serine in their bloodstream. However, while serine is essential for many biological processes, it was not known at that time to affect eye health.

In 2019, Friedlander and colleagues found the connection. They made a breakthrough discovery that low serine levels were responsible for a buildup of toxic lipids, which cause photoreceptor cells to die. But still, many questions remained. For example, what caused the decline in serine? The investigation continued.

In the new study, Rando Allikmets, PhD, of Columbia University, used an alternative approach to find genetic drivers of disease. Instead of assessing individual mutations in genes, he and his team analyzed groups of mutations, giving them a greater ability to identify disease-causing genes in a small population of people with MacTel.

One gene, PHGDH, had significantly more variants in MacTel patients than those without the disease. The team identified 22 rare variants in PHGDH which, together, account for approximately 3 to 4 percent of MacTel cases. Many more variants likely exist but haven't been found yet a challenge considering the small patient population with diverse genetic causes.

Implications for other diseases

PHGDH is a key enzyme that enables the body to make serine, and these studies provided the long-sought link to low serine observed in MacTel patients. Its function is essential for the health of neurons in the eye and elsewhere in the body.

Several of the gene variants identified in the study are known to cause rare, severe neuropathies when both of the alleles, or copies of the gene, are affected. In the case of MacTel, only a single allele is affected, resulting in a partial loss of the enzyme function, which leads to retinal degeneration.

Many of these variants in PHGDH were identified for the first time and were predicted to cause defects in the gene, and Friedlander's group worked to confirm this. They directly tested whether each of the multitude of variants identified in MacTel patients are actually harmful to PHGDH function, and found they were.

The PHGDH gene is essential for the production of serine, which plays a central role in cellular metabolism, says Kevin Eade, PhD, a former Scripps Research postdoctoral associate who is a senior scientist at the Lowy Medical Research Institute. Through genetic analyses and experiments in human-derived retinal tissue, we were able confirm that even a partial loss of PHGDH function can have a damaging effect on the retina.

The scientists then used human induced pluripotent stem cells to generate specialized retinal cells that contained one of the MacTel-associated PHGDH mutations. They found that a PHGDH mutation in these cells leads to the production of a toxic lipid previously shown to cause MacTel.

Vision for a therapy

By more fully understanding the role of PHGDH in MacTel, scientists are hopeful they can begin to map out potential treatment approaches.

We still have much to learn about this rare disease, including why systemic changes in serine metabolism leads to retinal degeneration, says Marin Gantner, PhD, senior staff scientist at the Lowy Medical Research Institute and doctoral graduate of Scripps Research. We have come such a long way in identifying links to the disease, and every step provides new insights that can be leveraged in creating a therapy.

The study, Serine biosynthesis defect due to haploinsufficiency of PHGDH causes retinal disease, was authored by Kevin Eade, Marin Gantner, Joseph Hostyk, Takayuki Nagasaki, Sarah Giles, Regis Fallon, Sarah Harkins-Perry, Michelle Baldini, Esther Lim, Lea Scheppke, Michael Dorrell, Carolyn Cai, Evan Baugh, Charles Wolock, Martina Wallace, Rebecca B. Berlow, David Goldstein, Christian Metallo, Martin Friedlander and Rando Allikmets.

The work was supported by the Lowy Family,
LINK: https://www.scripps.edu/news-and-events/press-room/2021/20210322-fried...
See more stories from scripps

Most recent headlines

13/03/2025

FCC Chairman Carr Launches Massive Deregulation Initiative

WASHINGTON FCC Chairman Brendan Carr announced that the agency has launched a massive, new deregulatory initiative that could potentially subject virtually all ...

13/03/2025

SDVI Integrates Rally With Spectra Vail

SUNNYVALE, Calif. SDVI has announced that it has integrated its Rally media supply chain management platform with the Spectra Vail multi-cloud data management s...

13/03/2025

FCC Approves Gray's Acquisition of KXLT

ATLANTA Gray Media has announced that the Federal Communications Commission (FCC) has granted a waiver of its local ownership rules to permit Gray Media to acqu...

13/03/2025

NAB Show 2025 Exhibitor Insight: Blackmagic Design

TV Tech: What do you anticipate will be the most significant technology trends at the 2025 NAB Show?...

13/03/2025

Watch Student Naomi Soleils Folk Pop Performance on The Voice

Watch Student Naomi Soleils Folk Pop Performance on The Voice The songwriting major sang Stars by Grace Potter and the Nocturnals during the blind auditions. ...

12/03/2025

Como o Impacto Cultural e Financeiro da Indstria Musical Define Seu Sucesso em 2025

O Spotify acaba de lan ar o relat rio Loud & Clear deste ano, uma vis o transpar...

12/03/2025

Cmo el impacto cultural y financiero de la industria musical define su xito en 2025

Spotify acaba de presentar el informe Loud & Clear de este a o, una mirada trans...

12/03/2025

Nourish Mind, Body, and Soul This Ramadan With Spotify

Ramadan, a period of profound spiritual significance for Muslims worldwide, is a time for fasting, prayer, reflection, and community. Enrich your experience thi...

12/03/2025

How the Music Industry's Cultural and Financial Impact Define Its Success in 2025

Spotify has just unveiled this year's Loud & Clear report, a transparent loo...

12/03/2025

FAST now transcends back catalog content

More than 70% of FAST programming has been produced since 2010, according to new Gracenote report NEW YORK March 12, 2025 Gracenote, the content data busin...

12/03/2025

Viamedia Adopts ShowSeeker Pilot To Streamline Ad Workflows

GEONA, Nev. Independent digital and linear advertising rep firm Viamedia will adopt cloud-based ShowSeeker Pilot as its primary ad campaign and order management...

12/03/2025

Mediagenix Appoints Wael Yasin as Sales Director Central Europe

BRUSSELS Mediagenix has announced that Wael Yasin has joined the company as sales director Central Europe....

12/03/2025

Omdia: Global Online Consumer Expenditure to Hit $6.6 Trillion by 2029

LONDON A new study highlights opportunities for shoppable TV and the massive impact online consumer spending is having on the economy, with Omdia predicting tha...

12/03/2025

Comcast Technology Solutions Upgrades to Interra Systems BATON Version 9

CUPERTINO, Calif. Interra Systems has announced that Comcast Technology Solutions has integrated recent updates to BATON Version 9 into its operations....

12/03/2025

Nevion announces new 400G addition to its eMerge SDN media fabric offering

Nevion announces new 400G addition to its eMerge SDN media fabric offering Brie Clayton March 12, 2025 0 Comments High-capacity switch enhances existi...

12/03/2025

DaVinci Resolve Studio Delivers Cinematic Sound for Adam Bol

DaVinci Resolve Studio Delivers Cinematic Sound for Adam Bol Brie Clayton March 12, 2025 0 Comments Feature film relies on DaVinci Resolve Studio for ...

12/03/2025

SVT Leverages Ateliere Live to Pioneer 100% Software-Defined Production at Rally Sweden 2025

SVT Leverages Ateliere Live to Pioneer 100% Software-Defined Production at Rally...

12/03/2025

Berklee Awards Fenway Neighborhood Improvement Grant to Four Organizations

Berklee Awards Fenway Neighborhood Improvement Grant to Four Organizations A total of $17,000 will be distributed among the Boston-based nonprofits. By Madd...

12/03/2025

Offering a broad umbrella for IP standards

TVBEuropes Jenny Priestley sits down with new SMPTE president Richard Welsh to discuss his aims for the organisation going forward, its efforts to attract a you...

12/03/2025

Warner Bros Belgium takes a new approach to its post production workflows

The new process has significantly enhanced operational efficiencies, with automation freeing up creators to concentrate on higher value tasks By Matthew Corrig...

12/03/2025

Another VFX company suspends operations

Jellyfish Pictures, which has offices in London and Sheffield, said it has been battling hard in the face of strong headwinds over the last 12 months By Jenny ...

12/03/2025

Bitcentral to Showcase AI-Powered Innovations for Smarter...

Visit Booth #W2213 to Experience the Latest in AI-Driven Content Discovery and Workflow Automation Bitcentral, a leader in media workflow solutions, is set to ...

12/03/2025

Jeff Lilly Named WGN-TV Director Of Technology

CHICAGO Jeff Lilly has been named WGN-TV director of technology effective March 17, 2025, according to Ric Harris, WGN-TV vice president and general manager....

12/03/2025

Survey: Consumers Want More Shoppable TV Experiences

MOUNTAIN VIEW, Calif. A new study from LG Ad Solutions indicates that consumers want more features that would allow them to shop for products on the connected T...

12/03/2025

IP Showcase To Focus On IP, Broadcast Tech Convergence at 2025 NAB Show

BOTHELL, Wash. The Alliance for IP Media Solutions (AIMS), Advanced Media Workflow Association (AMWA) and the Video Services Forum (VSF) will once again present...

12/03/2025

Comcast Boosts Internet Speeds for More Than 20 Million Customers

PHILADELPHIA Comcast announced that it has upgraded Xfinity Internet speeds for more than 20 million customers for no additional cost....

12/03/2025

Create with Maxon: Cinema 4D Fundamentals Workshop - March 12-14

Create with Maxon: Cinema 4D Fundamentals Workshop - March 12-14 Brie Clayton March 11, 2025 0 Comments Makin' Waffles with Elly Wade During Marc...

12/03/2025

Ross Video Strengthens Cloud Leadership with Appointment of Aaron Tunnell

Ottawa, Canada - March 12, 2025 - Ross Video is pleased to announce the appointment of Aaron Tunnell as Business Development Director, Cloud Solutions, reinforc...

12/03/2025

VEON to release 4Q 2024 trading update on 20 March 2025

12 Mar 2025 VEON to release 4Q 2024 trading update on 20 March 2025 Dubai, 12 March 2025 - VEON Ltd. (NASDAQ: VEON), a global digital operator, today confirms ...

12/03/2025

Getting Set for the Winter Olympics: Inside SVT's Ongoing Software-Based Production Evolution

Getting set for the Winter Olympics: Inside SVT's ongoing software-based pro...

12/03/2025

Seamless SMPTE 2110: A Discussion on Making the Move to IP Less Painful

Seamless SMPTE 2110: A Discussion on Making the Move to IP Less Painful Leaders from Netflix, Monumental Sports & Entertainment, LinkedI, and Megapixel address ...

12/03/2025

Opening Doors of Perception: Meta's Ajit Ninan on Rethinking AR/MR Perceptual Displays

Opening Doors of Perception: Meta's Ajit Ninan on Rethinking AR/MR Perceptua...

12/03/2025

Sky Sports Unveils Exciting Plans for 2025 Formula 1 Coverage

With the 2025 Formula 1 season set to begin in Melbourne on March 16, Sky Sports is gearing up to deliver its most comprehensive F1 coverage yet. Following a th...

12/03/2025

Unicanal and Trece TV revolutionize Digital TV in Paraguay with Rohde & Schwarz transmission solutions

Unicanal and Trece TV revolutionize Digital TV in Paraguay with Rohde & Schwarz ...

12/03/2025

Honoring Service, Celebrating Sport: Rohde & Schwarz UK Sponsors NavyFit Rugby Double-Header

Honoring Service, Celebrating Sport: Rohde & Schwarz UK Sponsors NavyFit Rugby D...

12/03/2025

FOR-A America Introduces Top of the Line HANABI Series Switcher at NAB 2025 Exhibition

New HVS-Q12 Represents a Quantum Leap in Switcher Design...

12/03/2025

Telespazio and ABS Expand Partnership to Deliver Tailored C-Band Connectivity Solutions for the Brazilian Market

Telespazio and ABS Expand Partnership to Deliver Tailored C-Band Connectivity So...

12/03/2025

Congratulations to all our clients who have achieved TAG certification through our independent validation

ABC conducts independent audits across the TAG programs. In the March 2025 TAG s...

12/03/2025

Moonlight: Thales Alenia Space to develop the space segment of the navigation system orbiting around the Moon

Facebook Twitter LinkedIn Moonlight: ESA program to create a satellite con...

12/03/2025

Thales among the world's top 100 most innovative companies for the 12th year, according to Clarivate

Facebook Twitter LinkedIn In 2025, Thales ranks among the top 0.01% of the...

12/03/2025

CCPC sponsored TV series The Complaints Bureau returns to RT One

Consumer show back following hugely successful first series 10 March 2025 Following a hugely successful first series, The Complaints Bureau returns to RT ...

11/03/2025

Give Me the Backstory: Get to Know Amel Guellaty, the Writer-Director of Where the Wind Comes From

By Lucy Spicer One of the most exciting things about the Sundance Film Festival...

11/03/2025

Salsa's Rhythmic Revival: A New Generation Discovers the Genre's Timeless Appeal

Salsa is making a comeback, captivating new listeners with its infectious energy...

11/03/2025

Canada's Own Rupi Kaur Curates the Latest Edition of Local Spot, Revealing the Songs and Artists That Shaped Her

For many people, music can serve as a reflection of their roots and upbringing. ...

11/03/2025

ST Engineering iDirect's Public Safety Solution Wins MSUA Satellite Mobile Innovation Award 2025

The solution delivers reliable, scalable and secure connectivity for critical pu...

11/03/2025

Weigel Broadcasting Taps Harmonic for Cloud-Based Playout-to-Delivery

SAN JOSE, Calif. Harmonic has announced that Weigel Broadcasting has deployed Harmonics VOS Media Software, which offers playout-to-delivery capabilities, inclu...

11/03/2025

Wheatstone To Unveil Linux Audio Driver At 2025 NAB Show

NEW BERN, N.C. Wheatstone will introduce a Linux audio driver for its WheatNet IP audio network during the 2025 NAB Show, April 5-9, at the Las Vegas Convention...

11/03/2025

Study: Women's Sports Are a Big Win for Advertisers

NEW YORK A new study finds that as TV viewership for women's sports surged by 131% in 2024, the programming also saw a 56% year-over-year increase in ad im...

11/03/2025

Al Sharqiya prepares for Ultra HD with FOR-A

Powerful switcher for news studio FOR-A, a cutting-edge video broadcast technology company backed by more than 50 years experience, has installed its HVS-1200 ...