Stem Cell Treatment May Restore Vision to Patients with Damaged Corneas

Newswise, June 6, 2017 — Researchers working as part of the University of Georgia’s Regenerative Bioscience Center have developed a new way to identify and sort stem cells that may one day allow clinicians to restore vision to people with damaged corneas using the patient’s own eye tissue. They published their findings in Biophysical Journa

The cornea is a transparent layer of tissue covering the front of the eye, and its health is maintained by a group of cells called limbal stem cells. But when these cells are damaged by trauma or disease, the cornea loses its ability to self-repair.

“Damage to the limbus, which is where the clear part of the eye meets the white part of the eye, can cause the cornea to break down very rapidly,” said James Lauderdale, an associate professor of cellular biology in UGA’s Franklin College of Arts and Sciences and paper co-author.

“The only way to repair the cornea right now is do a limbal cell transplant from donated tissue.”

In their study, researchers used a new type of highly sensitive atomic force microscopy, or AFM, to analyze eye cell cultures. Created by Todd Sulchek, an associate professor of mechanical engineering at Georgia Tech, the technique allowed researchers to probe and exert force on individual cells to learn more about the cell’s overall health and its ability to turn into different types of mature cells.

They found that limbal stem cells were softer and more pliable than other cells, meaning they could use this simple measure as a rapid and cost-effective way to identify cells from a patient’s own tissue that are suitable for transplantation.

“Todd’s technology is unique in the tiniest and most sensitive detection to change,” said Lauderdale. “Just think about trying to gently dimple or prod the top of an individual cell without killing it; with conventional AFM it’s close to impossible.”

Building on their findings related to cell softness, the research team also developed a microfluidic cell sorting device capable of filtering out specific cells from a tissue sample.

With this device, the team can collect the patient’s own tissue, sort and culture the cells and then place them back into the patient all in one day, said Lauderdale. It can take weeks to perform this task using conventional methods.

The researchers are quick to caution that more tests must be done before this technique is used in human patients, but it may one day serve as a viable treatment for the more than 1 million Americans that lose their vision to damaged corneas every year.

The group first started this research with the hope of helping children with aniridia, an inherited malformation of the eye that leads to breakdown of the cornea at an early age.

Because aniridia affects only one in 60,000 children, few organizations are willing to commit the resources necessary to combat the disease, Lauderdale said.

“Our first goal in working with such a rare disease was to help this small population of children, because we feel a close connection to all of them,” says Lauderdale, who has worked with aniridia patients for many years.

“However, at the end of the day this technology could help hundreds of thousands of people, like the military who are also interested in corneal damage, common in desert conditions.”

Steven Stice, a Georgia Research Alliance Eminent Scholar, who plays an important role in fostering cross-interdisciplinary collaboration as director of the RBC, initially brought the researchers together and encouraged a seed grant application through the center for Regenerative Engineering and Medicine, or REM, a joint collaboration between Emory University, Georgia Tech and UGA. “A culture is developing around seed funding that is all about interdisciplinary collaboration, sharing of resources, and coming together to make things happen,” said Stice.

“Government funding agencies place a high premium on combining skills and disciplines. We can no longer afford to work in an isolated laboratory using a singular approach.”

The REM seed funding program is intended to stimulate new, unconventional collaborative research and requires equal partnership of faculty from two of the participating institutions.

“We tend to get siloed experimentally,” says Lauderdale. “To a biologist like me, all cells are very different and all atomic force microscopes are the same. To an engineer like Todd it’s just the opposite.”

The study, “Cellular Stiffness as a Novel Stemness Marker in the Corneal Limbus,” is available at http://www.cell.com/biophysj/fulltext/S0006-3495(16)30771-8.

Funding was provided by an NIH NIGMS Biotechnology Training Grant on Cell and Tissue Engineering, the Knights Templar Eye Foundation, the Center for Regenerative Engineering and Medicine, the Sharon Stewart Aniridia Research Trust and the NSF CMMI division.

Assessing the Impact of Stress in Age-Related Macular Degeneration

Newswise, June 6, 2017– Age-related macular degeneration (AMD), the leading cause of vision loss among older adults in the United States, is often associated with psychological stress. 

A simple stress rating scale (the Perceived Stress Scale) is a valid and useful way to evaluate the connection between stress and progressive vision loss from AMD, according to a study in the March issue of Optometry and Vision Science, the official journal of the American Academy of Optometry. The journal is published by Wolters Kluwer.

"Because AMD is an inflammatory disease, we are studying the link between inflammation, stress, and AMD treatment outcomes," reported Bradley E. Dougherty, OD, PhD, of The Ohio State University College of Optometry. "In the end, we hope to better understand how general well-being influences disease outcomes."

Measuring Stress May Aid in Assessing the Life Impact and Progression of AMD--Patients with vision loss in AMD experience high rates of stress, anxiety, and other problems, including depression. Less is known about the relationship between the stress that AMD patients experience and the severity of their disease—for example, whether stress can cause AMD to worsen or not.

The Perceived Stress Scale (PSS) is a well-established stress rating scale that can predict objective biological markers of stress, as well as the risk of stress-related diseases. In previous studies, the PSS has been shown to be predictive of general markers of inflammation, including C-reactive proteins. In the new study, Dr. Dougherty and colleagues extend the use of this survey to determine how well it measures perceived stress in patients with vision loss due to AMD.

One hundred thirty-seven patients with AMD, average age 82 years, completed the ten-question PSS. Using a technique called Rasch analysis, Dr. Dougherty and colleagues evaluated the PSS's performance as a stress measure in AMD. About half of the patients filled out the stress questionnaire on a day when they received injections of anti-VEGF antibodies—a relatively new treatment that can slow the progression of the "wet" form of AMD.

Nine of the ten questions normally used with the PSS performed well with the patient group studied. These nine items were also able to separate between patients with higher versus lower levels of perceived stress. For some PSS items, responses differed according to patient age and visual acuity level.

However, the overall PSS score was not significantly related to the patients' visual acuity level. Average visual acuity in the better eye for this group of AMD patients was 20/50, with a range from near normal to very low vision.

"A psychometrically sound, easy-to-administer questionnaire such as the PSS is important for use with patients with AMD, given the evidence for increased rates of psychological symptoms in the population," Dr. Dougherty and coauthors write.

They note that stress-reduction approaches—for example, "mindfulness" interventions—have led to improved outcomes in patients with various health conditions.

Dr. Dougherty and colleagues also note that stress may be associated with increased inflammation and that AMD is an inflammatory disease—raising the possibility that stress may contribute to disease progression.

Future studies using repeated assessments with the PSS and measurement of inflammatory markers might provide evidence on how perceived stress levels affect the risk of AMD progression and worsening vision loss.

Click here to read “Measurement of Perceived Stress in Age-Related Macular Degeneration.”

New Clinical Trial for Early-Stage Eye Melanoma Offers Study of Targeted Therapy

Credit: Photo courtesy: Roger Barone / Wills Eye Hospital.

Wills Eye Hospital's Carol Shields, MD examines patient (clinical study participant). Oncology research fellow, wearing protective eyewear, also observes. 

Newswise, April 3, 2017 – A first-of-its-kind, potentially groundbreaking new option for treating a form of eye cancer is now in its first phase-1 clinical research trial at Wills Eye Hospital in Philadelphia.

The treatment, called light-activated AU-011, developed by Aura Biosciences of Cambridge, Massachusetts, is an investigational drug that targets and aims to selectively destroy malignant cancer cells in patients who have life-and vision-threatening eye cancer, also known as, ocular melanoma.

Ocular melanoma is a malignant cancer that develops within the eye. It affects as many as 3,000 people per year in the United States. While melanoma is often associated with skin cancer from sun exposure, ocular melanoma does not relate to the sun, developing instead from abnormal pigmented cells in the eye.

The danger with ocular melanoma is that there are often no symptoms, making it difficult to detect resulting in the potential of quietly spreading throughout other parts of the body.

Risk factors include being Caucasian, fair-skinned, and the risk of developing the disease also increases as we age. The best way to detect ocular melanoma is to have an annual comprehensive dilated eye exam by a board certified ophthalmologist.

This innovative treatment approach now being investigated at Wills Eye Hospital uses viral nanoparticle conjugates, which is a targeted therapy of growing interest in medicine.

The treatment involves injecting the AU-011 investigational drug into the eye affected by cancer followed by the brief use of a companion ophthalmic laser treatment to activate the drug.

The investigational drug is expected to destroy the membranes of the ocular melanoma while sparing key eye structures which may allow for the potential of preserving patients’ vision.

“Patients with ocular melanoma currently have few treatment options available that can effectively destroy tumor cells while preserving vision. Conducting valuable research trials like this one enables clinicians and researchers to examine new and better options for patients throughout the world,” said, Carol L. Shields, MD, Co-Director of the Ocular Oncology Service at Wills Eye Hospital where the first US patient was treated.

Dr. Shields is also a key investigator in the research trial and the author of numerous top peer-reviewed publications on ocular melanoma, including identification of the risk factors for early diagnosis (Kaliki & Shields 2016 in Nature Eye.)

Currently, the primary treatment option for ocular melanoma is plaque radiotherapy which was, in part, pioneered in the United States by the Shields Oncology team at Wills Eye Hospital.

While that therapy has achieved high success throughout the years in tumor control for patients, this new potential targeted therapy may open the door to a less invasive method of treatment.

“We are delighted to be one of the pre-eminent clinical trial sites in the nation for this unique and promising treatment. Wills Eye has always been a leader in the clinical application of emerging new therapies. We are 100% behind our world’s best oncology team,” said, Julia A. Haller, MD, Ophthalmologist-in-Chief, Wills Eye Hospital.

The trial, which began in early 2017, is expected to enroll up to 12 patients at Wills Eye and other clinical trial sites.

Trial investigators will focus on evaluating the safety of two dose levels of AU-011 for the treatment of patients with small to medium primary ocular melanoma. Potential participants must have a confirmed ocular melanoma diagnosis not previously treated. Patients treated in the trial will be observed and followed for 2 years.

About Carol L. Shields, MD: Dr. Carol Shields is Co-Director of the Oncology Service, Wills Eye Hospital, and Professor of Ophthalmology at Thomas Jefferson University in Philadelphia. She has authored or co-authored 9 textbooks, over 1000 articles in major journals, nearly 300 textbook chapters, given over 600 lectureships, and has received numerous professional awards of major national and international standing including The American Academy of Ophthalmology Life Achievement Honor Award.

Dr. Carol Shields is a member of numerous ocular oncology, pathology and retina societies and has delivered 30 named lectureships in America and abroad. She practices ocular oncology on a full time basis with her husband, Dr. Jerry Shields on the Oncology Service at Wills Eye Hospital.

About Wills Eye Hospital: Wills Eye Hospital is a global leader in ophthalmology, established in 1832 as the nation’s first hospital specializing in eye care. U.S. News & World Report consistently ranks Wills Eye as one of America’s top ophthalmology centers since the survey began and has the most nationally ranked ophthalmologists in the country.

Wills Eye is a premier training site for all levels of medical education. Its resident and post-graduate training programs are among the most competitive in the country. One of the core strengths of Wills is the close connection between innovative research and advanced patient care. Wills provides the full range of primary and subspecialty eye care for improving and preserving sight, including cataract, cornea, retina, emergency care, glaucoma, neuro-ophthalmology, ocular oncology, oculoplastics, pathology, pediatric ophthalmology and ocular genetics, and refractive surgery.

Ocular Services include the Wills Laser Correction Center, Low Vision Service, and Diagnostic Center. Its 24/7 Emergency Service is the only one of its kind in the region. Wills Eye also has a network of nine multi-specialty, ambulatory surgery centers throughout the tri-state area. To learn more, please visit www.willseye.org