Diabetic Retinopathy II: the beginning


In my last post I discussed the anatomy of the eye. Keep this in mind as we begin to consider what diabetes does to this anatomy. Remember that the most important aspect of diabetes is high blood sugar. This is the source of all complications that will make life so miserable down the line. The two major issues with glucose, as I have written before, are that it is reactive outside the cell and that it can get converted to sorbitol inside the cell.

The tissue at risk here are the capillaries and other small blood vessels in the choroid. These are the sources of nutrients for the retina which is the most metabolically active tissue in the body. We have a great deal of information about how diabetes changes these vessels at very early times in the disease. The early heroes who made this possible are the people who have specified that their bodies can be used for research after they die. Sadly, there are too many of them. Car accidents probably account for the vast majority along with heart attacks and cancer. People studying diabetic retinopathy put together a proposal to obtain eyes from these people after they die. Once the proposal is reviewed and accepted, specific hospitals would be set up as sources for the material and everything would be scrutinized carefully by ethics committees before the work began. Once the eyes were in hand, these researchers carefully examined the vascular structure of the choroid and compare it to the status of diabetes in the person before they died. In the present day, we have very powerful imaging tools that can examine many aspects of the retinal vasculature in the living patient – more on this later.

Those first researchers found interesting abnormalities in the vascular structure that supplies the retina and have associated this with very early times during the development of diabetes. First of all, they found that the walls of certain capillaries thicken. What do I mean by walls? Capillaries are, of course, made up of cells that create these tiny tubes through which the blood flows. However, what I am talking about is the stuff that is secreted just outside of these cells. We call this stuff “basement membrane”. Think of basement membrane kind of like a lattice of fibers. It is made up of collagen – you know…that stuff that some people inject to make their lips look fuller. Its real function is to create these lattice structures that surround tissues. All of the tissues of our body have basement membrane surrounding it. The lattice contains many important molecules that help information pass from tissue to tissue. This lattice is what gets thickened in places as diabetes progresses. Since nutrients need to pass from the capillaries to the RPE layer (see the previous post for the definition) to get to the photoreceptors it is probably no surprise that a thickening of the basement membrane will decrease the flow rate for these nutrients. This sets up a problem. Nutrients are no longer getting to the photoreceptors in that area fast enough. What happens is that the tissue begins to build up an oxygen debt – a state called ischemia. Let’s hold onto that thought for a while since we have to talk about some other changes to the vasculature.

In other capillaries researchers have found tiny ruptures (called microaneurysms). The presence of microaneurysms is considered the first sign of diabetic retinopathy in medical textbooks. We do not really know how this fits in with the pathology. Imaging can detect these microaneurysms so we can now see them in live patients and try to correlate them with the onset of diabetes and with diabetic retinopathy. The problem is that they don’t seem to correlate with any of the standard pathologies apart from the fact that we see them at the beginning of the disease.

In yet other capillaries we see something called pericyte ghosts. Pericytes are going to end up playing a big role in diabetic retinopathy so let’s spend a minute on them. Blood vessels tighten and relax. This is how blood pressure is regulated. It can let one organ get lots of blood while decreasing blood flow to another organ. In order for a blood vessel to tighten it needs a band of muscle to surround the vessel. This vascular smooth muscle is what does the job of squeezing and releasing. Really small blood vessels like arterioles, veinules, and the capillaries in between are too small. Instead they use pericytes. The pericyte surrounds the tiny tube at strategic spots and squeezes to create pressure. When they are missing we can tell. We see an outline of where they were positioned and we call this a pericyte ghost.

In still other capillaries we see a different kind of ghost. In imaging studies of patients it is possible to actually see blood flow through the capillaries. Actually, in pictures what we really see are the red blood cells in a line (the capillary is so small that red blood cells go through one at a time). In patients who are developing diabetic retinopathy we see whole capillary branches that appear empty.

So to sum up, we see lots of changes in the vascular bed of the retina long before the patient has any kind of problem with their vision. These changes are visible with current imaging techniques and unequivocally herald the onset of diabetic retinopathy. How long it takes to develop depends on how well the patient controls their glucose. Good glucose control can keep things under control for many years.

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