Science Current Events | Science News | Brightsurf.com
 

Joslin Researchers Discover Protein that Causes Blood Vessel Leakage in Eyes with Diabetic Retinopathy

January 30, 2007

Although health professionals have had success in treating diabetic retinopathy, two forms of the disease — proliferative diabetic retinopathy and diabetic macular edema — still are the leading causes of vision loss and blindness among working age adults in the developed world. Now a Joslin Diabetes Center-led team of investigators has compiled the most complete inventory yet available of the proteins present in a part of the human eye known as the vitreous and has identified a group of proteins that may play critical roles in causing blood vessel leakage in the eyes of people with this common form of diabetic eye disease.

In the new study, published in the Jan. 28 online edition of the journal Nature Medicine, lead investigator Edward Feener, Ph.D., and his team also found that one of these molecules causes the leakage of retinal blood vessels, which contributes to the retinal swelling (diabetic macular edema or DME) that is often associated with advanced diabetic retinopathy. These findings suggest potential new therapeutic targets for the treatment of diabetic retinopathy and DME and also could provide new opportunities for treating cerebral swelling caused by head injury, stroke and other conditions.

"By analyzing the protein composition in the human vitreous (the gel fluid that fills the cavity of the eye between the lens and the retina), we have identified a new group of molecules that may improve our understanding of the disease processes that contribute to diabetic retinopathy. By studying the actions of these proteins in both the retina and the brain, we have shown that our findings may have broad relevance for neurovascular leakage and swelling," said Dr. Feener, Investigator in Joslin's Section on Vascular Cell Biology, Director of Joslin's Proteomics Core, which hosted the study, and Assistant Professor of Medicine at Harvard Medical School.

The work was funded by grants from the Juvenile Diabetes Research Foundation (JDRF), the Massachusetts Lions Eye Research Fund, the National Institutes of Health, the Adler Foundation, and the Air Force Office of Scientific Research Medical Free Electron Laser Program.

"Millions of people worldwide live with diabetic retinopathy and the accompanying threat of severe vision loss or blindness. While some treatment is available in the late stages of this condition, the incidence of proliferative diabetic retinopathy and diabetic macular edema still pose the serious threat of sight loss. Going forward, Dr. Feener's findings could provide new opportunities for the development of treatments for diabetes-related vision loss," said Dr. Helen Nickerson, Scientific Program Manager for Complications at JDRF.

Diabetic retinopathy, one of the most common complications of diabetes, is characterized by a range of abnormalities that develop from the damage caused by high blood glucose levels on the small blood vessels of the retina. Proliferative diabetic retinopathy (PDR) is diagnosed when the retina begins to form new blood vessels to counteract this damage, new vessels which in turn often bleed and blur or block vision. More than 700,000 patients in the United States have PDR, and more than 63,000 patients develop it annually. Diabetic macular edema occurs as the leaky blood vessels cause the macula (the central area in the retina responsible for sharp central vision) to swell. DME affects more than 500,000 patients in the U.S., with 56,000 new cases diagnosed yearly.

In the past, researchers have had difficulty studying the pathology of both of these diseases because rodents with diabetes, which investigators often use as a laboratory model to study diabetic eye disease, do not naturally produce many of the changes in the retina that health professionals observe in humans. Dr. Feener and his colleagues developed cutting edge proteomics mass spectroscopy (a high-speed protein analysis technology) and bioinformatics at Joslin to identify protein abnormalities in the vitreous of people with and without diabetic eye disease. Then, they introduced these same proteins in the vitreous of rodents and examined their effects on retinal blood vessels to gain better understanding of the actions that these proteins could have in the eyes of people with diabetes.

Working with a network of collaborators at Joslin's Beetham Eye Institute and the Santa Barbara Cottage Hospital Eye Center in California, they obtained samples from the vitreous of 25 people undergoing surgery for a variety of conditions: eight of the patients did not have diabetes and therefore no diabetic eye disease; four had diabetes, but no diabetic retinopathy; and 13 had PDR. Launching a large-scale survey of the proteins in the vitreous, they identified 117 proteins (earlier attempts to catalog vitreous proteins had succeeded in identifying only 20 to 50) and detected 31 proteins that were present in the vitreous of patients with diabetes but weren't present in people without the disease.

One of the proteins that was particularly interesting was carbonic anhydrase 1, or CA-1. "This is an enzyme that is normally found in red blood cells; however we suspected that high levels of this protein in the vitreous fluid might cause problems," said Dr. Feener. "When we tested it in the vitreous of rodents, we found a marked increase in blood vessel leakage, which is a fundamental process in diabetic retinopathy."

Margaret Dunn, President of the Massachusetts Lions Eye Research Fund, Inc., said, "On behalf of the Lions of Massachusetts and the Massachusetts Lions Eye Research Fund, Inc., we wish to congratulate Joslin Diabetes Center on its important breakthrough. We pledge our full support now and in the future in the hope that we will be able to contribute to many future endeavors of the Joslin research team and applaud them on their wonderful accomplishments."

The mission of the Massachusetts Lions Eye Research Fund (MLERF) is to fund efforts in eye research that may one day lead to the prevention of blindness in the world. They play a unique role in eye research efforts, enabling avenues of research to be explored as preliminary studies that may ultimately lead to remarkable breakthroughs in our understanding of the causes of blindness. In this respect, the research team at Joslin's Beetham Eye Institute led by Sven-Erik Bursell, Ph.D., and Allen Clermont, M.S., were able to use funding from the MLERF to conduct the necessary experiments to characterize the physiological effect of these proteins and how they were exerting these abnormal effects.

The researchers then investigated several different lines of study and found that CA-1 increased retinal edema—the swelling of the retina. "This is the first evidence we have of a protein causing swelling, not just leakage, in the rodent at concentrations observed in human disease," said Dr. Feener.

Performing additional studies with CA-1, the researchers showed that their findings have even broader relevance. "The eye is a neurovascular tissue with certain features similar to those of the brain, and it is well known that hemorrhage in the brain, either from a hemorrhagic stroke or any cerebral bleeding, causes swelling," said Dr. Feener. "When we introduced CA-1 into the cerebral spinal fluid around the brain of rodent animal models we found that it also increased the swelling and the leakage of blood vessels in the brain." This discovery, he explained, could provide new opportunities for treating the cerebral swelling caused by head injury, stroke and other conditions.

"Proteomics of human vitreous fluid has generated new ideas about the effects of diabetes on the retina," said Dr. Feener. "Now we are in the process of exploring the role of the other proteins we have identified in the vitreous, which may provide additional insights into the mechanisms that contribute to diabetic retinopathy."

Others participating in the study included lead author, Ben-Bo Gao, Ph.D., of Joslin; additional collaborators from the Section on Eye Research and the Beetham Eye Institute at Joslin included Lloyd Paul Aiello, M.D., Ph.D., Susan Rook, Stephanie Fonda, Ph.D., Paul G. Arrigg, M.D.; Vivek Srinivasan, M.S., Maciej Wojtkowski, Ph.D., and James Fujimoto, Ph.D., of the Massachusetts Institute of Technology; and Robert Avery, M.D., of the Santa Barbara Cottage Hospital Eye Center.

Joslin Diabetes Center


Related Diabetic Retinopathy Current Events and Diabetic Retinopathy News Articles


USC study finds blindness and visual impairment will double by 2050
A study published today by researchers at the University of Southern California (USC) Roski Eye Institute in JAMA Ophthalmology found that the U.S. prevalence in visual impairment (VI) and blindness is expected to double over the next 35 years.

Eylea outperforms Avastin for diabetic macular edema with moderate or worse vision loss
A two-year clinical trial that compared three drugs for diabetic macular edema (DME) found that gains in vision were greater for participants receiving the drug Eylea (aflibercept) than for those receiving Avastin (bevacizumab), but only among participants starting treatment with 20/50 or worse vision.

Ranibizumab found effective against diabetic retinopathy
In a randomized clinical trial of more than 300 participants, researchers from Johns Hopkins and elsewhere have found that ranibizumab -- a drug most commonly used to treat retinal swelling in people with diabetes -- is an effective alternative to laser therapy for treating the most severe, potentially blinding form of diabetic retinal disease.

Lucentis effective for proliferative diabetic retinopathy
A clinical trial funded by the National Institutes of Health has found that the drug ranibizumab (Lucentis) is highly effective in treating proliferative diabetic retinopathy.

Lucentis proves effective against proliferative diabetic retinopathy
A clinical trial among more than 300 patients has found that the drug ranibizumab (Lucentis) is highly effective in treating proliferative diabetic retinopathy (PDR), a complication of diabetes that can severely damage eyesight.

Injection instead of laser may be viable treatment option for diabetic retinopathy
Among patients with proliferative diabetic retinopathy, treatment with an injection in the eye of the drug ranibizumab resulted in visual acuity that was not worse than panretinal photocoagulation at 2 years, according to a study appearing in JAMA.

For Latinos, African ancestry adds to risk of glaucoma
Latinos with African ancestry are at a higher risk for high pressure within the eye, a condition that if untreated can damage the optic nerve and impair vision, according to a report in the journal Ophthalmology.

New drug candidate is promising therapeutic option for angiogenic retinal diseases
A research team led by scientists at Beth Israel Deaconess Medical Center (BIDMC) and the University of New Mexico School of Medicine has identified a small molecule that treats animal models of aged macular degeneration (AMD) and retinopathy of prematurity (ROP) by preventing the overgrowth of blood vessels that are characteristic of these two retinal diseases.

Damage in retinal periphery closely matches loss of blood flow in people with diabetes
Research from the Joslin Diabetes Center's Beetham Eye Institute demonstrated earlier this year that in people with diabetic retinopathy, the presence of lesions in the periphery of their retina substantially increases the risk that the disease will progress more rapidly.

In diabetic eye disease, peripheral lesions in the retina point to risks of progression
For decades, clinicians have detected and monitored diabetic eye disease with standard retinal photographs that cover about a third of the retina. In recent years, an emerging class of ultrawide field (UWF) cameras has given a substantially larger view of the retina, providing new insight on the presentation and natural history of retinal disease.
More Diabetic Retinopathy Current Events and Diabetic Retinopathy News Articles

Diabetic Retinopathy

Diabetic Retinopathy
by Bruno, M.D. Lumbroso (Author), Marco, M.D. Rispoli (Author), Maria Cristina, M.D., Ph.D. Savastano (Author)


Diabetic Retinopathy is a concise guide to the condition caused by complications of diabetes, which can eventually lead to blindness. The book is edited by a team of experts from the Italian Macular Centre in Rome, led by Prof Bruno Lumbroso. Divided into ten chapters, the book begins with basic information on diabetes and diabetic retinopathy. Further chapters demonstrate how to read and interpret different forms of imaging, including fluorescein angiography, cross-section OCT, and 'en-face' OCT. Information on the use of the most recent OCT angiography imaging techniques brings this book fully up to date. 73 full colour images and illustrations enhance the text, which highlights the importance of clinical imaging in everyday treatment of diabetic retinopathy. Diabetic Retinopathy is an...

Diabetic Retinopathy for the Comprehensive Ophthalmologist, Second Edition

Diabetic Retinopathy for the Comprehensive Ophthalmologist, Second Edition
by Jonathan Walker, Robert B. Chambers Raj K. Maturi (Author)


This book is designed to transfer useful techniques for the clinical management of diabetic patients. It is an attempt to go beyond the results of clinical trials and to address the nuances of treating diabetics by compressing the clinical experience of the authors into a format that hopefully makes it easy to expand your skills. The book is written for residents, beginning retina fellows, and comprehensive ophthalmologists--as well as for anyone interested in broadening their understanding of these complex patients. More information is available at the website drcobook.com.

Diabetic Retinopathy: From Diagnosis to Treatment

Diabetic Retinopathy: From Diagnosis to Treatment
by David S. Boyer MD (Author), Homayoun Tabandeh MD (Author)


The most common eye disease among those with type 1 or type 2 diabetes is diabetic retinopathy and this book explains the disease, how it develops, and options for treatment. Affecting more than five million Americans, the disease is caused by damage to the tiny blood vessels of the retina as the result of uncontrolled blood sugars, and is a leading cause of blindness. Diabetic retinopathy cannot be cured, however the onset can be delayed and the risk of progression can be reduced by keeping tight controls on glucose levels and making the right lifestyle choices. This guide will help both patients and their families by covering such topics as symptoms, stages of the disease, how it is diagnosed, treatment options, ways to slow its progression, and lifestyle changes that lead to better...

Diabetic Retinopathy: The Essentials

Diabetic Retinopathy: The Essentials
by Gloria Wu MD (Author)


Diabetic Retinopathy: The Essentials is written for general ophthalmologists and optometrists as well as family practitioners, diabetologists, and internists who encounter diabetic patients on a daily basis. It focuses on the diagnosis and management of diabetic retinopathy from the point of view of the retinal specialist. The book begins with the epidemiology, anatomy, and pathophysiology of diabetic retinopathy, and then covers important topics such as classification issues, diagnostic testing, examination techniques, new treatment modalities, patient management, indications for vitrectomy, pregnancy concerns, and informed consent. Coverage includes both general medical issues in diabetes and specifically ophthalmologic concerns. Features include more than 200 full-color photographs,...

Diabetic Retinopathy Atlas

Diabetic Retinopathy Atlas
by Vishali Gupta (Author), Amod Gupta (Author), M.R. Dogra (Author), Ramandeep Singh (Author)


A comprehensive, uniquely focused management guide to diabetic retinopathy Because few texts focus exclusively on diabetic retinopathy, Diabetic Retinopathy Atlas is both timely and time-saving, a one-of-a-kind source of state-of-the-art diagnostic and treatment techniques for dealing with this affliction. Offered throughout are hands-on guidelines for performing the eye screenings, laser photocoagulation, and surgery that prevent or manage the visual impairment caused by diabetic retinopathy. Incorporates current information on all aspects of diabetic retinopathy into actual patient management strategies Targets essential information within each chapter with succinct, time-saving key points sections 600 full-color photos and illustrations
A DVD provides 38 videos showing...

Diabetes: Chapter 22. Antioxidant Supplements and Diabetic Retinopathy

Diabetes: Chapter 22. Antioxidant Supplements and Diabetic Retinopathy
by Academic Press


Conventional treatments for diabetic retinopathy (DR) includes glycemic control, laser photocoagulation, vitrectomy, intravitreal triamcinolone, and intravitreal anti-vascular endothelial growth factor agents. However these strategies have not proved capable of halting the progression of this disease in all cases. The mechanisms leading to DR are not fully understood, but there is a growing body of evidence showing that oxidative stress plays a pivotal role in the development of this diabetic complication. In fact it has been proposed that oxidative stress is the initial and maintaining event that triggers and provides feedback to the other pathophysiological pathways related to DR. The experimental data discussed in this review show that different antioxidant agents may prevent various...

Diabetes: Chapter 4. Diabetic Retinopathy and Oxidative Stress

Diabetes: Chapter 4. Diabetic Retinopathy and Oxidative Stress
by Academic Press


Diabetic retinopathy (DR) is the leading cause of acquired blindness in working age adults worldwide. Biochemical changes in DR contribute to both the microscopic structural and functional changes in the retina. All these alterations result in macroscopic retinal damage that can be assessed by funduscopy. The overproduction of reactive oxygen species (ROS) in the mitochondria is considered a causal link between elevated glucose and biochemical abnormalities in the pathophysiology of DR. Moreover, oxidatively induced pathways also seem to provide positive feedback to ROS production, resulting in a vicious cycle. ROS can directly damage lipids, proteins and DNA, leading to cell death. To make the situation worse, antioxidant defenses are also impaired in diabetes. Otherwise, ROS are...

Clinical Strategies in the Management of Diabetic Retinopathy: A step-by-step Guide for Ophthalmologists

Clinical Strategies in the Management of Diabetic Retinopathy: A step-by-step Guide for Ophthalmologists
by Francesco Bandello (Editor), Marco Attilio Zarbin (Editor), Rosangela Lattanzio (Editor), Ilaria Zucchiatti (Editor)


With the advent of effective treatments for diabetic retinopathy (DR), a new era in the management of DR has been opened up. Amid the deluge of approved treatments and promising new strategies, however, clinicians may find it difficult to choose the appropriate practice in each individual case. The purpose of this easy-to-use and richly illustrated manual is to assist ophthalmologists in making decisions in the entire management of DR based on the best available evidence. Practical and complete recommendations are provided to guide clinicians in diagnosis, decision-making, and treatment. The manual includes practical algorithms and case histories relating to all stages of DR that clearly explain the progression of the disease and will help the clinician to choose the best therapeutic...

Diabetic Retinopathy: Causes, Tests, and Treatment Options

Diabetic Retinopathy: Causes, Tests, and Treatment Options
by Dale Carter MA (Author), Edward Montgomery (Editor)


Diabetes mellitus is a disease that is rapidly increasing in prevalence worldwide, particularly in Canada and the United States. One of the most common complications for all types of diabetes mellitus is diabetic retinopathy, a disease that is currently the leading cause of blindness among adults in the United States and Canada. It is estimated that at least 40% of Americans and Canadians with diabetes mellitus have some clinically detectable form of diabetic retinopathy, and statistics are similar worldwide. This invaluable book contains all the information you need to know about the causes, tests and treatment options available to combat this sight-threatening disorder.

Diabetic Retinopathy: From Screening to Treatment (Oxford Diabetes Library Series)

Diabetic Retinopathy: From Screening to Treatment (Oxford Diabetes Library Series)
by Paul Dodson (Editor)


Current guidelines state that 100% of patients with diabetes should be screened for retinal problems. This pocketbook is a concise companion for professionals involved in sreening and treating diabetic retinopathy (DR). It explains why screening is required, the different screening models available with their advantages and disadvantages, and the different DR grades. The book also describes specific problems such as ophthalmic lesions, which may present themselves as DR and covers the treatment of DR from both a medical and an ocular perspective.

This book is presented in full color and contains over 100 images. Each chapter is written with a specfic role in a DR screening scheme.

© 2016 BrightSurf.com