Of all the diabetic complications to fear – blindness may be the most scary and is certainly devastating when it occurs. Diabetic retinopathy causes from 12,000 to 24,000 cases of blindness each year according to the National Institutes of Diabetes and Digestive and Kidney Disease (NIDDK); one of the National Institutes of Health that funds much of diabetes research in the US. Perhaps 50% of newly diagnosed diabetes patients (we are talking type II here) have some degree of retinal damage. In part this is due to the very long time between onset of hyperglycemia associated with pre-diabetes and the actual diagnosis of the condition.
I bring up this topic now because next week is the national meeting of the Association for Research in Vision and Ophthalmology (ARVO) where some of the new information about diabetic retinopathy research and treatment will be presented. (A lot also gets presented at the American Diabetes Association annual meeting as well.) I will be attending and, time willing, I will try to file some reports on what I see and hear over the next week.
In preparation, let’s talk about the eye and about retinopathies. The eye is an outpouching of the brain. It is an incredible sensory organ that can detect just a few photons. We can divide the eye into the part that focuses light: the lens and the part that detects light: the retina. Each photoreceptor cell within the retina is sort of like a little electric circuit. It sends electrically charged small molecules called ions through tiny holes called ion channels. It is the movement of these ions that creates the electric circuit. Photons which pass through the photoreceptors are absorbed by a protein called rhodopsin and thus detected. When the photon hits rhodopsin the protein changes shape subtly and this initiates a signaling pathway in the photoreceptor cell that leads to the closing of those ion channels. This changes the electric current and voila – you see something. Vision, of course, requires a lot more information processing. That blip of electric current gets passed to a layer of intermediate nerve cells in the eye (amacrine and bipolar cells) where the signal from that piece of the visual field is compared to other bits of information coming in from neighboring regions and the information begins to be put together into larger pieces. These get passed to another neuron called the ganglion cell which sends the information back to the visual centers of the brain through the optic nerve.
Surprisingly, the retina appears to be constructed backwards. You would think that the photoreceptor cells would be facing outward towards the light and that the nerve cells that process the information would sit behind the photoreceptors. This is reversed. The photoreceptors are in the back of the eye and the light must pass through the ganglion cells and other nerve cells to get to the photoreceptors. Weird.
One reason that things may be set up this way is that photoreceptors need constant maintenance. I think that the electric current I described above takes a lot out of the photoreceptor. Indeed the retina is the most metabolically active tissue in the body. Rhodopsin sits within discs which are stacked like rings in a large cylinder. The tips of the photoreceptor cells are in close contact with another tissue at the very back of the eye called the retinal pigment epithelium (RPE). As the photoreceptors cells toss out their trash the RPE must gobble it up, keeping the environment clean. The RPE also reprocess several chemicals that the photoreceptors need to function. Thus the RPE are working as hard as the photoreceptors. Behind the RPE lie the blood vessels that supply all of those wonderful nutrients that keep the show running. This point ends up being very important for our understanding of how things go wrong for people with diabetes.
Remember that sugar is reactive. I’ve talked about this before. This is one reason why diabetes is so deadly. In the eye, a strange thing happens. Glucose as well as its derivative, sorbitol, causes the blood vessels behind the retina begin to thicken in spots. The thickening has an evil consequence. Since the photoreceptors are so metabolically active they cannot handle even a little loss in blood flow. Like us, when expenses get a bit too heavy, they begin to run up a debt. In this case the debt is in oxygen. Interestingly, when the tissues of the retina notice that they are running up an oxygen debt they activate special genes that are designed to initiate the growth of new blood vessels. One such gene encodes the growth factor VEGF (vascular endothelial growth factor). VEGF binds to receptors on the cells of these blood vessels and they respond by sprouting new branches. This, by itself would not be so bad, except the process does not stop. The blood vessels grow into the retina and disrupt the highly organized structure of the photoreceptors. Furthermore, the new blood vessels are quite leaky and fluid gets into the retina blocking photoreceptor access to light. The result, as you might imagine, is not good.
There is little in the way of treatments. Within the past few years drugs that block VEGF have hit the market and have helped. These include Avastin and Leucentis. Still, we have a long way to go.
At any rate, if I see something interesting and worth reporting during ARVO, you will ready about it here.