 |
|
Transporters may help delay diabetes-related retinal damage
November 29, 2007Two transporters that deliver alternative energy sources to the eye may help delay retinal damage that can occur in diabetes, researchers say.
The transporters, SMCT1 and SMCT2, can circumvent the eye's protective blood-retinal barrier, delivering energy sources lactate and ketone bodies to a healthy eye, says Dr. Pamela Martin, biochemist at the Medical College of Georgia.
In diabetes, characterized by plenty of glucose but the inability of cells to use it, the retina may turn to those alternate sources for survival.
"Glucose is your primary energy source," says Dr. Martin. "But in diabetes, the retina undergoes a lot of stress, there is oxidative damage and a lot of other things going on. These transporters, we believe, may be instrumental in bringing in additional substrates which the cells can use for energy to try and prevent death."
Diabetic retinopathy, the leading cause of blindness in working-age adults, results in death of retinal neurons, at least in part because glucose availability is compromised for this high-energy-consuming tissue, says Dr. Martin.
She suspects the two transporters work harder in diabetes to increase levels of lactate and ketones bodies, which may help explain why diabetes' impact on the eye may go undiagnosed for years. "I think what fascinates me so much about the eye is you can have diabetes for more than 20 years before you or your doctor realize that you have diabetic retinopathy," says Dr. Martin.
Understanding how these transporters work normally and in diabetes may enable early diagnosis of diabetic retinopathy and natural delivery mechanisms for drugs to stop it.
Dr. Martin was a postdoctoral fellow in the lab of Dr. Vadivel Ganapathy, chair of the MCG Department of Biochemistry and Molecular Biology who first cloned the SMCT1 and SMCT2 transporters, before she joined the faculty in 2005. She was first author on a paper published this year in Investigative Ophthalmology and Visual Science that showed the presence of the transporters in the retina.
Now she is one of four investigators nationally to receive a Pathway to Independence Award for new investigators from the National Eye Institute that will help her elucidate these transporters' activity in healthy and diseased states.
Lactate and ketone bodies are substances called monocarboxylates and previously there was no evidence that transporters that typically haul these substances around are elevated in diabetes. But these monocarboxylate transporters, or MCTs, are more passive than the recently discovered, sodium-coupled SMCT1 and SMCT2 which are "driven," able to go against the concentration gradient and change substrates, like lactate, from low to high concentrations inside the cells, says Dr. Martin.
"If you have these transporters, they can transport these substrates into your retina and hopefully prevent some of the neuronal cell damage that occurs," Dr. Martin says.
An aggressive vehicle is necessary since, like the brain, the retina has a natural barrier to prevent many substances in the blood from reaching the eye.
The MCG researcher has shown SMCT1 is expressed in retinal neurons and in the retinal pigmented epithelium, one of the back layers of the multi-layer retina that is important in terms of transporting good things in and waste products out. SMCT2 is primarily expressed in supportive retinal Müller cells.
One of the many questions she wants to answer is whether they play different roles in these different cell types.
She's using two diabetic mouse models, one that develops type 1 diabetes at about three weeks, which is comparable to children developing the disease in their first few years of life. The second is a mouse she makes diabetic, so she will know the precise moment it happens.
She'll look at the expression, activity and function of these transporters in both models and is optimistic she'll find them helpful to diabetics.
"The damage still occurs, people still go blind from diabetic retinopathy, but it may delay it," says Dr. Martin. "But what if we could find some pharmacologic agents they could transport into the eye and save it?"
Dr. Ganapathy, who is Dr. Martin's mentor for the NIH grant, also is working on SMCT1 and its role in the colon where his experimental evidence indicates it has a tumor-suppressive role. In the colon, SMCT1 transports short-chain fatty acids such as butyrate, which is generated by bacterial fermentation of dietary fiber. The transporter is silenced in colon cancer but when colon cancer cells are forced to express it, they die in the presence of butyrate.
"The normal bacteria present in our colon are doing a lot of good things to benefit us," Dr. Ganapathy says. "These findings may explain the age-old knowledge that dietary intake of fiber is protective against colon cancer."
Dr. Martin is a 2003 graduate of the MCG School of Graduate Studies.
Medical College of Georgia
"Glucose is your primary energy source," says Dr. Martin. "But in diabetes, the retina undergoes a lot of stress, there is oxidative damage and a lot of other things going on. These transporters, we believe, may be instrumental in bringing in additional substrates which the cells can use for energy to try and prevent death."
Diabetic retinopathy, the leading cause of blindness in working-age adults, results in death of retinal neurons, at least in part because glucose availability is compromised for this high-energy-consuming tissue, says Dr. Martin.
She suspects the two transporters work harder in diabetes to increase levels of lactate and ketones bodies, which may help explain why diabetes' impact on the eye may go undiagnosed for years. "I think what fascinates me so much about the eye is you can have diabetes for more than 20 years before you or your doctor realize that you have diabetic retinopathy," says Dr. Martin.
Understanding how these transporters work normally and in diabetes may enable early diagnosis of diabetic retinopathy and natural delivery mechanisms for drugs to stop it.
Dr. Martin was a postdoctoral fellow in the lab of Dr. Vadivel Ganapathy, chair of the MCG Department of Biochemistry and Molecular Biology who first cloned the SMCT1 and SMCT2 transporters, before she joined the faculty in 2005. She was first author on a paper published this year in Investigative Ophthalmology and Visual Science that showed the presence of the transporters in the retina.
Now she is one of four investigators nationally to receive a Pathway to Independence Award for new investigators from the National Eye Institute that will help her elucidate these transporters' activity in healthy and diseased states.
Lactate and ketone bodies are substances called monocarboxylates and previously there was no evidence that transporters that typically haul these substances around are elevated in diabetes. But these monocarboxylate transporters, or MCTs, are more passive than the recently discovered, sodium-coupled SMCT1 and SMCT2 which are "driven," able to go against the concentration gradient and change substrates, like lactate, from low to high concentrations inside the cells, says Dr. Martin.
"If you have these transporters, they can transport these substrates into your retina and hopefully prevent some of the neuronal cell damage that occurs," Dr. Martin says.
An aggressive vehicle is necessary since, like the brain, the retina has a natural barrier to prevent many substances in the blood from reaching the eye.
The MCG researcher has shown SMCT1 is expressed in retinal neurons and in the retinal pigmented epithelium, one of the back layers of the multi-layer retina that is important in terms of transporting good things in and waste products out. SMCT2 is primarily expressed in supportive retinal Müller cells.
One of the many questions she wants to answer is whether they play different roles in these different cell types.
She's using two diabetic mouse models, one that develops type 1 diabetes at about three weeks, which is comparable to children developing the disease in their first few years of life. The second is a mouse she makes diabetic, so she will know the precise moment it happens.
She'll look at the expression, activity and function of these transporters in both models and is optimistic she'll find them helpful to diabetics.
"The damage still occurs, people still go blind from diabetic retinopathy, but it may delay it," says Dr. Martin. "But what if we could find some pharmacologic agents they could transport into the eye and save it?"
Dr. Ganapathy, who is Dr. Martin's mentor for the NIH grant, also is working on SMCT1 and its role in the colon where his experimental evidence indicates it has a tumor-suppressive role. In the colon, SMCT1 transports short-chain fatty acids such as butyrate, which is generated by bacterial fermentation of dietary fiber. The transporter is silenced in colon cancer but when colon cancer cells are forced to express it, they die in the presence of butyrate.
"The normal bacteria present in our colon are doing a lot of good things to benefit us," Dr. Ganapathy says. "These findings may explain the age-old knowledge that dietary intake of fiber is protective against colon cancer."
Dr. Martin is a 2003 graduate of the MCG School of Graduate Studies.
Medical College of Georgia
Diabetic Retinopathy News and Current Diabetic Retinopathy Events RSSCognitive problems associated with diabetes duration and severity
Individuals with mild cognitive impairment appear more likely to have earlier onset, longer duration and greater severity of diabetes, according to a report in the August issue of Archives of Neurology, one of the JAMA/Archives journals.
Study shows pine bark naturally reduces cardiovascular risk factors in diabetics
A new study published in the May 2008 (volume 8, issue 25) edition of the journal of Nutrition Research shows Pycnogenol (pic-noj-en-all), an antioxidant plant extract from the bark of the French maritime pine tree, reduces blood sugar in type II diabetes patients, allows people to lower their antihypertensive medication and improves cardiovascular disease (CVD) risk factors.
Moran Eye Center researchers find gene linked to severe diabetic eye and kidney diseases
Researchers at the John A. Moran Eye Center at the University of Utah and collaborative institutions have identified a gene called erythropoietin (EPO) that contributes to increased risk of severe diabetic eye and kidney diseases, called retinopathy and nephropathy.
Scientists uncover the potential to control adult stem cells
Research being presented today (10 April) at the UK National Stem Cell Network Annual Science Meeting in Edinburgh represents a step towards the use of Adult Stem Cells (ASCs) to repair damaged tissue.
Blood vessel protein reverses macular degeneration, diabetic retinopathy in mice
Two major eye diseases and leading causes of blindness-age-related macular degeneration and diabetic retinopathy-can be reversed or even prevented by drugs that activate a protein found in blood vessel cells, researchers at the University of Utah School of Medicine and several other institutions have announced in a new study.
'Fluorescent' cells give early warning for eye disease
Scientists at the University of Michigan have shown that their new metabolic imaging instrument can accurately detect eye disease at a very early stage.
Protein controls blood vessel formation, offers new drug target
After an injury, the body grows new blood vessels to repair damaged tissue. But sometimes too much growth causes problems, as when new blood vessels in the eyes leak, causing diabetic retinopathy and blindness if not treated.
'Twinkle after-effect' can help retinal patients detect vision loss quickly and cheaply
Scientists at Schepens Eye Research Institute, an affiliate of Harvard Medical School, have discovered a simple and inexpensive way for patients with retinal and other eye disease to keep track of changes in their vision loss.
'Twinkle after effect' can help retinal patients detect vision loss quickly and cheaply
Scientists at Schepens Eye Research Institute have discovered a simple and inexpensive way for patients with retinal and other eye disease to keep track of changes in their vision loss.
Use of insulin pen may save diabetics thousands of dollars
Diabetics who need to switch from oral medications to insulin could reduce their annual health care costs up to $17,000 by using an insulin pen instead of a syringe to deliver their daily dose of medication. A new study found that using an insulin pen may result in fewer trips to the emergency department and to the doctor's office, resulting in substantial savings to diabetics and their insurers.
More Diabetic Retinopathy News Articles
 | Medical Retina (Essentials in Ophthalmology) The specialty of medical retina remains one of the most challenging fields in ophthalmology. Fortunately, in the past few years the standard of knowledge in the area of medical retina has improved substantially. The insight in basic mechanisms of disease has been expanded and novel diagnostic and efficacious therapeutic strategies have been developed bridging the gap between laboratory and... |
 | Handbook of Retinal Screening in Diabetes by Roy Taylor This book, a successor to the highly popular Practical Guide to Polaroid Retinal Photography, describes the essential components of a retinopathy screening programme, including the criteria for referral to an ophthalmologist, drawing upon the experience of the Newcastle system over the last two decades and the National Screening Committee Report upon Eye screening. It is fully illustrated,... |
| Ocular complications of diabetes (Clinical symposia) by Charles A Garcia Dr. Bob Rotella, whose clients include Nick Price, Davis Love III, Tom Kite and Pat Bradley, is firmly established as the premier performance enhancement specialist in the golf world. In Golf is a Game Of Confidence, "Doc" Rotella focuses on the most important skill a golfer can have: the ability to think confidently.Confidence, or "playing with your eyes," can be the difference between making... | |
 | Diabetic Retinopathy Atlas by Vishali Gupta Comprehensive, uniquely focused management guide to diabetic retinopathy Because few texts focus exclusively on diabetic retinopathy, Diabetic Retinopathy Atlas is both a timely and time-saving, one-of-a-kind source of state-of-the-art diagnostic and treatment techniques for dealing with this... |
| Vascular Complications of Diabetes: Current Issues in Pathogenesis and Treatment Diabetes has reached epidemic proportions, and the cardiovascular complications of diabetes are life-threatening and disabling. This book is unique in providing a simple explanation of the biochemical role of PKC in diabetes complications, which allows clinicians to understand why PKC inhibitors (in development) are an exciting prospect for future treatment to slow progression of eye & foot... | |
| He Saw a Hummingbird: 2 by Norma Lee Browning, Russell Ogg Despite severe diabetes, Russell Ogg was a successful photographer who traveled worldwide with his wife, journalist Norma Lee Browning. He's always been able to cope with anything, but when diabetes began to rob him of his sight, "it was like a violinist losing his fingers." When Norma Lee saw him sitting day after day on the patio of their home in Palm Springs, slumped in despair, his sightless... | |
 | Diabetic Retinopathy (Developments in Ophthalmology) Diabetic retinopathy (DR), damage of the blood vessels in the retina, is one of the problems that patients may face as a complication of diabetes and is, along with other diabetic eye diseases, the greatest single cause of blindness in developed countries. This publication starts with the description of the mechanisms of development and progression of diabetic macular edema and with the... |
| Atlas of diabetic retinopathy: A photographic study (Steno Memorial Hospital and the Nordisk Insulinlaboratorium. Report) by Hans Walther Larsen | |
| Retinopathy found prior to diabetes.(Diabetic retinopathy): An article from: Internal Medicine News by Miriam E. Tucker This digital document is an article from Internal Medicine News, published by Thomson Gale on August 15, 2005. The length of the article is 722 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser.Citation DetailsTitle:... | |
| Diabetic Nephropathy: Strategy for Therapy (Developments in Nephrology) |
| © 2008 BrightSurf.com |