Transporters may help delay diabetes-related retinal damage

Two 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.