Keith Hautala

By

College: Medicine

Insight Into Major Cause of Age-Related Blindness

Published: Feb 9, 2011



To view a transcript of the video, click the attachment below the photo viewer. Video by Jenny Wells/UK Public Relations.

LEXINGTON, Ky. (Feb. 7, 2011) − A team of researchers, led by University of Kentucky ophthalmologist Dr. Jayakrishna Ambati, has discovered a molecular mechanism implicated in geographic atrophy, the major cause of untreatable blindness in the industrialized world.

Their article, "DICER1 Deficit Induces Alu RNA Toxicity in Age-Related Macular Degeneration," was published online by the journal Nature on Feb. 6 (DOI: 10.1038/nature09830). 

Concurrent with this discovery, Ambati's laboratory developed two promising therapies for the prevention of the condition. This study also elaborates, for the first time, a disease-causing role for a large section of the human genome once regarded as non-coding "junk DNA."

Geographic atrophy, a condition causing the death of cells in the retina, occurs in the later stages of the "dry type" of macular degeneration, a disease affecting some 10 million older Americans and causing blindness in over 1 million. There is currently no effective treatment for geographic atrophy, as its cause is unknown.

Ambati's team discovered that an accumulation of a toxic type of RNA, called Alu RNA, causes retinal cells to die in patients with geographic atrophy. In a healthy eye, a "Dicer" enzyme degrades the Alu RNA particles.

"We discovered that in patients with geographic atrophy, there is a dramatic reduction of the Dicer enzyme in the retina," said Ambati, professor and vice chair of the Department of Ophthalmology and Visual Sciences and the Dr. E. Vernon and Eloise C. Smith Endowed Chair in Macular Degeneration Research at the UK College of Medicine. "When the levels of Dicer decline, the control system is short-circuited and too much Alu RNA accumulates. This leads to death of the retina."

Alu elements make up a surprisingly large portion — about 11 percent by weight — of the human genome, comprising more than 1 million sequences. However, their function has been unknown, so they have been called “junk” DNA or part of the "dark" genome. The discovery of Alu’s toxicity and its control by Dicer should prove of great interest to other researchers in the biological sciences, Ambati says.

Ambati's team developed two potential therapies aimed at preventing geographic atrophy and demonstrated the efficacy of both approaches using laboratory models. The first involves increasing Dicer levels in the retina by “over-expressing” the enzyme. The second involves blocking Alu RNA using an “anti-sense” drug that binds and degrades this toxic substance. UK has filed patent applications for both technologies, and Ambati’s group is preparing to start clinical trials by the end of this year.

Response from the scientific community has been enthusiastic.

"These findings provide important new clues on the biological basis of geographic atrophy and may provide avenues for intervention through preventing toxic accumulation of abnormal RNA products," said Dr. Paul Sieving, director of the National Eye Institute. 

“Ambati’s latest research provides important mechanistic insights in geographic atrophy, and identification of this novel pathway may result in new therapeutic targets for a major cause of blindness,” said Dr. Napoleone Ferrara, a member of the National Academy of Sciences and Lasker-DeBakey awardee who is a researcher at Genentech.

This work has "widespread implications" for future study, said Dr. Stephen J. Ryan, president of the Doheny Eye Institute and member of the Institute of Medicine. “The authors have opened an important line of research with real possibilities for future therapeutic intervention for patients with geographic atrophy,” Ryan said.

Ambati's laboratory is supported by the National Eye Institute and Research to Prevent Blindness. Dr. Ambati is a Doris Duke Charitable Foundation Distinguished Clinical Scientist and Burroughs Wellcome Fund Translational Research Clinical Scientist.

MEDIA CONTACT: Keith Hautala, (859) 257-1754 ext. 231; keith.hautala@uky.edu

ambati-4-panel..jpg
September
 
 
 
 
1
Louis Zoellar Bickett: Saving Myself
LGBTQ* and Friends Employee Picnic
Thu
2
Louis Zoellar Bickett: Saving Myself
Fri
3
Louis Zoellar Bickett: Saving Myself
Sat
4
Louis Zoellar Bickett: Saving Myself
Sun
5
Louis Zoellar Bickett: Saving Myself
Labor Day - Academic Holiday
Mon
6
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Wildcat Wellness Workshop: EXPRESSIONS
Tue
7
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Let's Talk!
Wildcat Wellness Workshop: MEDITATION
UK Women's Club Volleyball - Open Gym
From The Streets to The Stage With Monti Washington
Wed
8
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Wildcat Wellness Workshop: YOGA
#IAMACCEPTANCE Let's Talk Mental Health with Hakeem Rahim
Thu
9
Louis Zoellar Bickett: Saving Myself
Let's Talk!
2016 New Chinese Students Welcome Party
Accounting Internship & Career Fair
Question, Persuade, Refer (QPR) Suicide Prevention Training
Fri
10
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Sat
11
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Whipping In The Kitchen
Sun
12
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Let's Talk!
Mon
13
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Wildcat Wellness Workshop: EXPRESSIONS
UKWC Welcome Coffee
Tue
14
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Last Day to Drop a Course Without Appearing on Transcript
Let's Talk!
Wildcat Wellness Workshop: MEDITATION
Greek Park Pictures
Wed
15
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Let's Talk!
Let's Talk!
Wildcat Wellness Workshop: YOGA
Thu
16
Louis Zoellar Bickett: Saving Myself
Let's Talk!
A Day of Rising Strong
Fri
17
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Sat
18
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Sun
19
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Let's Talk!
Mon
20
Louis Zoellar Bickett: Saving Myself
Let's Talk!
UK Women's Forum Board Meeting
UK Elder Care Lunch & Learn - Best Friends Approach to Dementia Care
Wildcat Wellness Workshop: EXPRESSIONS
Cuban Heritage Festival
Tue
21
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Last Day to Withdraw to Receive 50% Refund
Let's Talk!
Wildcat Wellness Workshop: MEDITATION
Horticulture Club Farm Market Sale
Wed
22
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Let's Talk!
Let's Talk!
Wildcat Wellness Workshop: YOGA
TGIT with SAB
Thu
23
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Fri
24
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Sat
25
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Film Screening of "The Fly Room"
Sun
26
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Film Screening of "The Fly Room"
Let's Talk!
Empower: People of Color Support Group
Film Screening of "The Fly Room"
Mon
27
Louis Zoellar Bickett: Saving Myself
Let's Talk!
FIFA Tournament
Wildcat Wellness Workshop: EXPRESSIONS
UK Engineering and Computer Science Career Fair
Banned Books--A short history
Tue
28
Louis Zoellar Bickett: Saving Myself
Let's Talk!
FIFA Tournament
Let's Talk!
Wildcat Wellness Workshop: MEDITATION
Horticulture Club Farm Market Sale
Cats Got The Vote
Business Internship & Career Fair
Women In Technology Gala event for UK undergraduate women
Wed
29
Louis Zoellar Bickett: Saving Myself
Let's Talk!
FIFA Tournament
Let's Talk!
Let's Talk!
Wildcat Wellness Workshop: YOGA
Yoga at Commonwealth Stadium
Thu
30
Louis Zoellar Bickett: Saving Myself
Let's Talk!
Indonesia Focus Conference
Indonesia Focus Conference
Craft Writing: Beer, the Digital, and Craft Culture
Fri
 
Sep 26
Let's Talk! 09/26/2016

Repeats every week until Mon Dec 05 2016 .
Mon, 09/26/2016

Mon, 09/26/2016

Repeats every 7 days until Tue Dec 13 2016 .
Tue, 09/27/2016

Tue, 09/27/2016 - Thu, 09/29/2016

Tue, 09/27/2016

Reset Page