Diabetes and the synthesis of synaptic proteins in the retina

This project is a study of the underlying causes of vision loss due to diabetes. Diabetic retinopathy is a leading cause of vision loss and one of the most common complications of diabetes. This project will focus on the possibility that vision loss in diabetes is due to abnormalities in the neurons of the retina, which carry information from the light-sensitive cells known as photoreceptors (also known as rods and cones) through the retina to the optic nerve, which carries information to the brain. The retina contains several types of neurons that are connected together and transmit information from one to the next, processing and refining the information at each step in the chain of cells, before ultimately delivering the visual signal to the brain to be interpreted. For communication between these different types of neurons to be effective, millions of connections, called synapses, must be formed between the neurons. The experiments proposed here will focus on the synapses between the neurons of the retina, and how diabetes may alter the way these connections work. It is very likely that loss of vision in diabetes is due to a failure of the synapses in the retina to work correctly. Diabetic rats are a widely-used animal model of Type I diabetes. This project will induce diabetes with a toxin called streptozotocin, which causes the rat to become diabetic 2-3 days after a single dose. This project will study several proteins that are uniquely found in neuronal synapses in the retina. The synaptic proteins are called synaptophysin, synapsin 1, VAMP2 and SNAP25. Each of these proteins fulfills a specific function in communication between neurons. The Principal Investigator has recently found that the amount of these proteins is reduced in the retinas of diabetic rats, within the first month of diabetes. This project will examine how diabetes changes the way these proteins are made in the retina, and whether using a class of drugs called calcium channel blockers can improve the production of these proteins in the hope of slowing the rate of vision loss in persons with diabetes.