von Gersdorff team sheds light on how diabetes triggers blindness

Diabetic  neuron
These retinal neurons are the first neurons to be damaged by diabetes. On the right is a micro-electrode used to fill the neuron with a dye to show its shape and to measure the tiny signals from the neuron’s synapse

A new study published in Neuron,  led by Henrique von Gersdorff, Ph.D., is the first characterization of a group of specialized synapses in the retina, the part of the eye that captures and transmits visual signals. These specialized synapses are inhibitory synapses that reduce the activity (or normal ‘chatter’) between neurons connected by multiple excitatory synapses. von Gersdorff and his team–Veeramuthu Balakrishnan, Theresa Puthussery, Mean-Hwan Kim, and W. Rowland Taylor–from the Vollum and Casey Eye Institutes developed a new, exquisitely sensitive technique to directly record and measure the properties of these synapses.

In addition to providing critical new insight into the basic processes of synaptic development in the retina, this study provides a deeper understanding of the critical synapses that may be damaged in pre-diabetic patients. A major complication of late-stage diabetes is that people go blind because of extensive damage to the synapses of the retina. The findings in this study lay a foundation for the development of drug treatments to prevent such blindness–in other words, they may lead to exciting new avenues for treatments of diabetic retinopathy at an early stage of the disease, before it has caused major damage to the retina. With diabetes, the process of retina damage takes some time. If scientists can develop neuro-protective drugs that can be directly injected into the eyes early on before blood vessels are damaged, they may be able to prevent irreversible loss of vision.

It wasn’t until earlier this year that a Norwegian study discovered that inhibitory synapses were affected by diabetes. However, very little is known about them because they are small and inaccessible. The OHSU team was able to advance their electrophysiological techniques to capture the signals from these synapses.

von Gersdorff argues that whenever you study fundamental mechanisms, down the line, you find that they are essential for understanding and curing human diseases. The insights from basic research are invaluable for developing treatment strategies. He says that even apart from the clinical implications, this study of fundamental mechanisms is intrinsically important because it increases our knowledge of how the retina and the brain work.

The title is “Synaptic Vesicle Exocytosis at the Dendritic Lobules of an Inhibitory Interneuron in the Mammalian Retina”; Neuron: 87:563-75.  This work was supported by grants from the National Institutes of Health National Eye Institute (EY014043, EY024265, and EY014888).