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Cell Models Reveal a Shared Early Pathway to Macular Disorders

Wednesday, December 27, 2017

Ruchira Singh, PhD, of the University of Rochester is hopeful that different macular disorders could potentially be stopped by treatments aimed at some of the earliest cellular changes that these diseases have in common. This new understanding comes from her recent research showing there are similarities in the lead-up to different forms of macular degeneration that might lend themselves to shared treatment approaches.

It’s good news, because shared therapies might be less costly to develop and use than separate therapies for each disease subtype, and could possibly be more effective at earlier stages.

Singh is using her 2015-18 Macular Degeneration Research (MDR) grant to study the role of different cells in the eye that are affected in age-related macular degeneration (AMD).

What makes her lab’s work stand out, in particular, is that it replicates early aspects of macular degeneration in cell models created from living cells of adult humans. Whereas earlier forms of stem cell research relied on cells from embryonic tissue, this 21st century variation, called human induced pluripotent stem cell (hiPSC) technology, uses stem cells gathered from living adults, and then reprogrammed to differentiate into eye cells.  iPSCs can self-renew and differentiate into nearly all cell types in the body.

Read More: Cell Models Reveal a Shared Early Pathway to Macular Disorders

Singh to study gene’s function in promoting retinal disease

Sunday, October 29, 2017

The retinal pigment epithelium (RPE) is a single layer of cells at the back of the eye that plays an indispensable role in supporting the light gathering photoreceptor cells that allow us to see. It is often thought of as a site where many blinding diseases begin, such as age related macular degeneration (AMD).

FEI Assistant Professor of Ophthalmology, Ruchira Singh, Ph.D., was recently awarded $1.95 million to study the role a gene called TIMP3 plays in regulating the extracellular matrix (ECM). The RPE’s ECM provides structural and biochemical support to the RPE, which is necessary for normal function of RPE cells. In some retinal diseases, ECM abnormalities are linked to RPE dysfunction, suggesting that the ECM may be at the root.

Mutations to the TIMP3 gene, and its effect on the ECM, are responsible for Sorsby’s Fundus Dystrophy (SFD). This disease closely mimics AMD. Singh, proposes to create a living tissue model of RPE-ECM using patient-derived human pluripotent stem cells (hiPSC) taken from subjects with SFD. To achieve this, she harvests skin cells from a person with SFD, re-programs them into stem cells and then differentiates them into unique cell types that model the RPE-ECM diseased cells.

Using this model, Singh will study the fundamental biology underlying SFD and the role that TIMP3 dysfunction plays in regulating a sequence of events that result in signs of SFD, such as the formation of drusen and the eventual growth of unwanted blood vessels in the retina. The knowledge gained in this study will help identify potential drug therapies for treating SFD. These may also prove useful in treating other retinal maculopathies such as AMD.

UR Medicine Uses ‘Bionic Eye’ to Restore Some Vision to Blind Syracuse Woman

Monday, October 23, 2017

A 71-year-old woman blinded by an inherited disease recently thrilled University of Rochester doctors by reaching out and grabbing her ophthalmologist’s hand after receiving a “bionic eye.”  The device allows her to distinguish light and motion, which she hasn’t been able to do in decades.

“I saw his hand – I couldn’t miss that,” said Khaleda Rahman, a Syracuse-area resident who once competed in the Olympics. 

She is the first person in New York to receive the FDA-approved Argus II Retinal Prosthesis System. There are fewer than 100 people in the U.S. that have the device, designed for people who have lost their vision as a result of retinitis pigmentosa.

“We dedicate our careers to restoring and improving vision and preventing vision loss. The ability to see someone who couldn’t see before, start to see again is very rewarding,” said Mina Chung, M.D. of the Flaum Eye Institute.  She worked with retina specialist Ajay Kuriyan, M.D., and anesthesiologist Anil Pisharoty, M.D., to implant the device Aug. 29 and then the ophthalmologists activated it Sept. 24.

“When she reached out and grabbed Dr. Kuriyan’s hand and they kind of held hands together. That was pretty exciting,” Chung said.  “I think it’s going to be an amazing advance for her.”

Retinitis pigmentosa is a rare, hereditary disease that causes progressive degeneration of the light-sensitive cells of the retina, leading to blindness. It affects about 1.2 million people worldwide and there is no treatment.  

Read More: UR Medicine Uses ‘Bionic Eye’ to Restore Some Vision to Blind Syracuse Woman

New Stem Cell Model Replicates Macular Degeneration

Tuesday, September 26, 2017

Photo of Human induced pluripotent stem cell-retinal pigment epithelium in a dish

Human induced pluripotent stem cell-retinal pigment epithelium in a dish.

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 (URMC).

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 RPB Career Development Award recipient Ruchira Singh, PhD, 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.”

Read More: New Stem Cell Model Replicates Macular Degeneration

New Model for Hard-to-Study Form of Blindness Paves Way for Future Research

Friday, September 15, 2017

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 skin cells from patients with genetic forms of macular degeneration, re-programmed them to stem cells, 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.

Read More: New Model for Hard-to-Study Form of Blindness Paves Way for Future Research

Aby Joseph Wins 2017 Leica Imaging Award

Tuesday, September 5, 2017

Congratulations to Aby Joseph, winner of the 2017 Leica Imaging Award for his time-lapse imaging of retinal microglia. Aby was honored with the award at the 2017 Immune Imaging Symposium at the University of Rochester.

Professor Buckley receives 2017 University Research Award

Monday, June 5, 2017

Professor Buckley has been awarded a 2017 University Research Award to pursue a promising project that has the potential to eventually leverage external funding. He will evaluate two approaches to minimizing the loss of corneal endothelial cells during cornea transplants. The project is titled, "Protection of corneal endothelial cells from surgical trauma.”

Abstract:

More than 65,000 vision-restoring corneal transplantations take place every year for individuals with corneal disease, corneal injury (e.g., from cataract surgery) and corneal scarring. Unfortunately, 30% of corneal grafts fail within 20 years. The most common reason for transplanted corneal grafts to fail is loss of corneal endothelial cells (CECs), the cells that line the inside of the cornea and pump fluid from it to maintain its transparency. Many of these cells are killed due to contact with tools and other materials during transplantation surgery. Thus, there is a need for new approaches that prevent CEC death during corneal grafting.

Using a custom testing platform developed in our laboratory, our preliminary experiments suggest that changes in the cytoskeleton (the network of structures within a cell that give it its shape) of CECs greatly protect these cells from injury due to mechanical contact. That is, when cells contain fewer stress fibers – thick cytoskeletal filaments that, like muscle, exert a contractile force – mechanical vulnerability is reduced. Based on these findings, we hypothesize treatments known to reduce the presence of stress fibers in cells will protect CECs from mechanical injury during corneal transplantation. In Aim 1, we will test whether chemical treatment with three agents that interfere with stress fibers – BAPTA, blebbistatin and the anti-metabolite 5-fluorouracil – reduces CEC death when the endothelium is contacted with a controlled force (simulating surgical manipulation). In Aim 2, motivated by the previous finding that fewer CEC stress fibers are observed in corneas preserved at low temperatures, we will test whether CECs are less vulnerable to mechanical trauma when the cornea is colder. This study is a key first step towards establishing chemical treatments (Aim 1) and maintenance of the cornea at cold temperatures during surgery (Aim 2) as promising methods to limit surgical trauma-associated CEC loss during corneal transplantation and reduce risk of graft failure. These approaches may also be applicable to other eye surgeries that can damage the corneal endothelium, including cataract surgery.

Commentary on Stem Cell Therapies: If You’re Asked to Pay, Walk Away

Monday, May 15, 2017

By Ajay Kuriyan, MD, MS

Stem cell clinics around the country are offering experimental treatments to cure a myriad of ailments - from multiple sclerosis and paralysis to vision loss. However, these unproven treatments can cost patients thousands of dollars and potentially cause devastating side effects. 

While serving as chief resident and co-director of Ocular Trauma at Bascom Palmer Eye Institute in Miami, FL, I was part of a team that took care of a patient who had blinding complications after receiving injections into her eyes at a stem cell clinic. She was charged $5,000 for the injection of stem cells that were isolated from her own body fat into both of her eyes, in hopes of halting the progressive vision loss caused by age-related macular degeneration.

Within days of the stem cell injections she was nearly blind and ultimately progressed to complete blindness. Two other patients who underwent similar treatments at the same clinic are also now legally blind after complications of the injections. Case studies of these three patients were published as a brief report today in the New England Journal of Medicine.

These patients provide an unfortunate example of what can go wrong when stem cell procedures are not appropriately regulated. Stem cell clinics have cropped up all over the US in recent years and are operating in a self-perceived regulatory loophole.  They argue that deriving stem cells from a patient’s own body and minimizing manipulation of those cells should excuse them from the level of Food and Drug Administration (FDA) oversight used to vet traditional drugs.

The FDA, however, has stated that stem cells ought to be held to the same regulatory standard as any other drug, citing the complexity of mammalian cells, the manipulation needed to isolate stem cells, and the difficulty of predicting how these cells will react to different environments (i.e. different tissues of the body).

Read More: Commentary on Stem Cell Therapies: If You’re Asked to Pay, Walk Away

Duje Tadin Awarded NARSAD Independent Investigator Award from the Brain and Behavior Research Foundation

Tuesday, April 25, 2017

Recently Dr. Duje Tadin, Associate Professor in Brain and Cognitive Sciences and at the Center for Visual Science won the NARSAD Independent Investigator Award from the Brain and Behavior Research Foundation. The title of his project is “A critical role of perceptual inefficiencies in working memory abnormalities in schizophrenia”. He also has a pending application to the Simons Foundation’s SFARI Pilot Awards program with a project titled “Functional consequences of elevated internal noise in autism.”

Well done!!

Retraining the Brain to See After Stroke

Wednesday, April 12, 2017

New study details “physical therapy” for eyes

photo of a man working with the retraining task

DeMay fixes his gaze on a live image of his own eye
in preparation for the next round of training.

Patients who went partially blind after suffering a stroke regained large swaths of rudimentary sight after undergoing visual training designed by researchers at the University of Rochester Medical Center’s Flaum Eye Institute.

A new study out today in Neurology®, the medical journal of the American Academy of Neurology, provides the first evidence that rigorous visual training recovers basic vision in cortically blind patients with long-standing stroke damage in the primary visual cortex. Damage to this area of the brain prevents visual information from getting to other brain regions that help make sense of it, causing loss of sight in one-quarter to one-half of an individual’s normal field of view. Somewhere between 250,000 and 500,000 people suffer vision loss due to damage to the visual cortex each year.

“We are the only people in the U.S. currently using this type of training to recover vision lost after damage to the primary visual cortex,” said study senior author Krystel Huxlin, Ph.D., director of Research and James V. Aquavella, M.D. Professor of Ophthalmology at URMC’s Flaum Eye Institute. “If you talk to the majority of clinicians, they still believe nothing can be done.”

Read More: Retraining the Brain to See After Stroke

URMC Recognizes 3 With Satcher Community Health Awards

Monday, April 10, 2017

Three individuals were honored Tuesday with the eighth annual Dr. David Satcher Community Health Improvement Awards, presented by the University of Rochester Medical Center’s Center for Community Health in the Helen Wood Hall Auditorium.

The Dr. David Satcher Community Health Improvement Awards distinguish individuals who have made significant contributions to community health in the greater Rochester region through research, education, clinical services and outreach efforts. The awards – named in honor of the 16th Surgeon General of the United States, who completed his medical residency at URMC in 1972, received an honorary degree from the University in 1995, and for two decades has served as an advisor to the medical center to move forward its community health mission – reflect the Medical Center’s mission to continue expanding university-community partnerships that support participatory research and interventions that reduce health inequalities and improve the community’s health.

Awards recipients for 2017 are:

Read More: URMC Recognizes 3 With Satcher Community Health Awards

Dr. Richard Libby Awarded 2017 Shaffer Prize for Innovative Glaucoma Research

Friday, February 17, 2017

Dr. Libby (center) receives the 2017 Shaffer Prize from GRF

For his research project “Understanding Axonal Degeneration Pathways in Glaucoma,” Richard T. Libby, PhD from the University of Rochester Medical School in Rochester, New York was awarded the 2017 Shaffer Prize for Innovative Glaucoma Research.

The Shaffer Prize was presented during ceremonies at the Glaucoma 360 Annual Gala on February 2nd at the Palace Hotel in San Francisco. The Shaffer Prize is awarded annually by Glaucoma Research Foundation to recognize a researcher whose project best exemplifies the pursuit of innovative ideas in the quest to cure glaucoma.

Thomas M. Brunner, President and CEO of the Glaucoma Research Foundation, presented the Shaffer Prize to Dr. Libby. Mr. Brunner explained the significance of the research results to Gala guests: “A 2015 Shaffer Grant allowed Dr. Libby’s lab to explore a novel new idea in the field of neurodegeneration, defining the molecular cascade that controls axon degeneration, which is a key early event in glaucoma,” he said.

Dr. Libby is an Associate Professor at the University of Rochester Medical Center, School of Medicine and Dentistry. He has previously received awards and honors including the Research to Prevent Blindness Career Development Award. Funding for Dr. Libby’s 2015 research project “Understanding Axonal Degeneration Pathways in Glaucoma” was provided by a grant from The Alcon Foundation.

Read More: Dr. Richard Libby Awarded 2017 Shaffer Prize for Innovative Glaucoma Research

Flaum Eye Institute Joins International Microsoft Intelligence Network for Eyecare

Monday, February 13, 2017

This past December, the LV Prasad Eye Institute and Microsoft India launched the Microsoft Intelligence Network for Eyecare (MINE), an international consortium of research institutions aimed at improving eye care worldwide. The University of Rochester Medical Center’s Flaum Eye Institute is one of five institutions partnering with Microsoft to share data and apply artificial intelligence to better understand eye diseases and improve eye care delivery around the world.

"The Flaum Eye Institute is proud and excited to be a part of this international network,” said Steven E. Feldon, M.D., M.B.A., chair of the Department of Ophthalmology. “The network will offer great opportunities to leverage data science and preventative medicine to improve vision worldwide, which aligns with several elements of University of Rochester and URMC strategic plans."

MINE will allow Flaum Eye Institute researchers to share Electronic Health Record information with partners at LV Prasad Eye Institute (India), Bascom Palmer - University of Miami (USA), Federal University of Sao Paolo (Brazil), and Brien Holden Vision Institute (Australia). Not only will this vastly increase the volume of data at each institution’s disposal, but will also add geographic, socioeconomic, and genetic diversity.  

In addition to sharing data, MINE will provide each partner institution with access to a trove of Microsoft analytical tools, which utilize machine learning to determine patterns and predict outcomes in eye care.

“A lot of institutions don't have access to these Microsoft tools,” said Rajeev S. Ramchandran, M.D., M.B.A., associate professor of Ophthalmology at URMC. “This helps democratize or level the playing field - not only sharing data, but also sharing the tools to analyze it.”

Read More: Flaum Eye Institute Joins International Microsoft Intelligence Network for Eyecare

A Closer Look at the Eye: Researchers Develop New Retinal Imaging Technique

Thursday, January 5, 2017

photo of David Williams

David Williams, Ph.D.

Researchers at the University of Rochester Medical Center have developed a new imaging technique that could revolutionize how eye health and disease are assessed. The group is first to be able to make out individual cells at the back of the eye that are implicated in vision loss in diseases like glaucoma. They hope their new technique could prevent vision loss via earlier diagnosis and treatment for these diseases.

In a study highlighted in the Proceedings of the National Academy of Sciences, Ethan A. Rossi, Ph.D., assistant professor of Ophthalmology at the University of Pittsburgh School of Medicine, describes a new method to non-invasively image the human retina, a layer of cells at the back of the eye that are essential for vision. The group, led by David Williams, Ph.D., Dean for Research in Arts, Sciences, and Engineering and the William G. Allyn Chair for Medical Optics at the University of Rochester, was able to distinguish individual retinal ganglion cells (RGCs), which bear most of the responsibility of relaying visual information to the brain.

Read More: A Closer Look at the Eye: Researchers Develop New Retinal Imaging Technique