New model for hard-to-study form of blindness paves way for future research

September 6, 2017, University of Rochester Medical Center
Credit: University of Rochester Medical Center

Macular degeneration is the leading cause of vision loss in older adults, but scientists have long struggled to study and replicate key elements of the disease in the lab. A study published in the Proceedings of the National Academy of Sciences is the first to demonstrate hallmarks of macular degeneration in a new human stem cell model developed by researchers at the University of Rochester Medical Center.

This new model could make whole new avenues of macular degeneration research possible and has helped the team hone in on some possible drug targets for the disease.

"So far, there has not been a patient-derived model of macular degeneration," said Ruchira Singh, Ph.D., assistant professor of Ophthalmology in the Flaum Eye Institute at URMC and lead author of the study. "It was not known if you can take cells from the human eye and make a cell model that displays the hallmarks of the disease."

Though macular diseases can vary widely, age-related and similar inherited macular degenerative diseases are all characterized by buildup of debris in the retina, the light sensing tissue in the back of the eye that is crucial for vision. These deposits, called drusen, are specifically found beneath a layer of retinal pigment epithelium (RPE) cells, which are known to be key players in macular degeneration.

For their new model, Singh's team collected from patients with genetic forms of macular degeneration, re-programmed them to , and used the stem cells to create RPE cells. RPE cells derived from patients mimicked several characteristics of macular degeneration when aged in a dish, like producing the hallmark deposits.

RPE cells carrying macular degeneration-causing mutations developed more deposits with more similar composition to what is seen in the affected human eye than cells from healthy adults, or patients' cells in which disease-causing mutations were corrected using gene editing.

Using this model, Singh's group showed for the first time that dysfunctional RPE cells can cause specific aspects of macular degeneration on their own - without the help of other cells or components of the retina. This was true for cells derived from patients with three different genetic forms of macular degeneration, suggesting RPE cell dysfunction could be central to multiple forms of the disease.

Singh's also allowed her research team to identify a group of molecules in RPE cells that could be targeted by new macular degeneration drugs. These "complement proteins", which normally boost immune functions in cells, may be affected by genetic alterations that cause macular degeneration. In the study, the expression of genes that encode these proteins was elevated in RPE cells from all of the macular degeneration patients, suggesting they may also play a key role in multiple forms of the disease.

"Now we can actually identify and test a rational drug therapy in patients' own cells," said Singh. "So far, this has not been possible, but now we can actually study macular diseases in parallel and identify what might be the central defect across macular diseases."

Singh believes this study will help move the field of macular degeneration research toward developing new drugs that target RPE , while providing a new and improved to screen those drugs. Though this work is early, the team hopes it will lead to an effective treatment for in the future.

Explore further: Study suggests stem cells may repair dying retinal cells

More information: Drusen in patient-derived hiPSC-RPE models of macular dystrophies, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1710430114 , http://www.pnas.org/content/early/2017/09/01/1710430114

Related Stories

Study suggests stem cells may repair dying retinal cells

January 21, 2016
Researchers at St. Erik Eye Hospital and Karolinska Institutet have for the first time successfully transplanted human retinal pigment epithelial cells derived from stem cells into eyes that are similar to human eyes. The ...

Levodopa shows promise against macular degeneration

November 13, 2015
(HealthDay)— Levodopa (L-dopa) might hold potential for preventing or treating macular degeneration, according to a study published online Oct. 30 in The American Journal of Medicine.

Study shows daily aspirin intake can lead to blindness

October 5, 2011
(Medical Xpress) -- A new study published in Ophthalmology reveals that while taking a daily aspirin may reduce the risks of heart disease and stroke, a disturbing side effect has also been noted to increase the risk of developing ...

Clinical trial tests cord-blood cells to treat macular degeneration

July 20, 2016
UIC is part of a national phase 2 clinical trial to evaluate the safety and tolerability of using cells derived from multipotent umbilical cord cells to treat age-related macular degeneration, the most common cause of vision ...

Stem cell injection may soon reverse vision loss due to age-related macular degeneration

April 14, 2015
An injection of stem cells into the eye may soon slow or reverse the effects of early-stage age-related macular degeneration, according to new research from scientists at Cedars-Sinai. Currently, there is no treatment that ...

Drusen as promising biomarkers for progression of macular degeneration

June 7, 2017
Age-Related Macular Degeneration (AMD) is a common disease of the centre of the retina, primarily affecting those aged over 50. The first signs of the disease are so-called drusen, which occur under the retina in the form ...

Recommended for you

Fetal gene therapy prevents fatal neurodegenerative disease

July 16, 2018
A fatal neurodegenerative condition known as Gaucher disease can be prevented in mice following fetal gene therapy, finds a new study led by UCL, the KK Women's and Children's Hospital and National University Health System ...

New study finds that fat consumption is the only cause of weight gain

July 13, 2018
Scientists from the University of Aberdeen and the Chinese Academy of Sciences have undertaken the largest study of its kind looking at what components of diet—fat, carbohydrates or protein—caused mice to gain weight.

Basic research in fruit flies leads to potential drug for diseases afflicting millions

July 13, 2018
River blindness and elephantiasis are debilitating diseases caused by parasitic worms that infect as many as 150 million people worldwide. They are among the "neglected tropical diseases" for which better treatments are desperately ...

Light based cochlear implant restores hearing in gerbils

July 12, 2018
A team of researchers with members from a variety of institutions across Germany has developed a new type of cochlear implant—one based on light. In their paper published in the journal Science Translational Medicine, the ...

Researchers discover gene that controls bone-to-fat ratio in bone marrow

July 12, 2018
In an unexpected discovery, UCLA researchers have found that a gene previously known to control human metabolism also controls the equilibrium of bone and fat in bone marrow as well as how an adult stem cell expresses its ...

Intensive care patients' muscles unable to use fats for energy

July 12, 2018
The muscles of people in intensive care are less able to use fats for energy, contributing to extensive loss of muscle mass, finds a new study co-led by UCL, King's College London and Guy's and St Thomas' NHS Foundation Trust.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.