Note to self: when someone asks you to write a book chapter…run. I do not think I have absorbed so much new information in such a short time since my neurophysiology class back in grad school (or pulled so many late night writing sessions).
The chapter has the tremendously exciting title: “Druggable Targets and Therapeutics for Diseases of the Back of the Eye”. I do not think it will hit the NYT best seller list but it will be of use to clinicians interested in the latest therapeutics and current clinical trials for the next generation therapeutics. It is now in the hands of the editor and so I am free Free FREE. Sorry.
At any rate, one of the sections in my chapter concerns the varied forms of diabetic retinopathy so I thought I would share a bit of it here (rewritten for the non-clinician).
Diabetes is one of the major causes of blindness in the industrialized world. We call the condition “retinopathy” because it is the retina that is affected. Vision loss is linked to glucose control. Keep your A1C levels below 6.5 and you are not at risk. This, of course, is pretty hard to do unless you are a very disciplined individual who exercises relentlessly. Generally, what clinicians see is that the average patient with type 2 diabetes has some degree of retinopathy upon diagnosis. It is subclinical at that point and will remain subclinical for quite a few years. Vision loss is gradual. Early stages are reversible but late stages are irreversible.
In order to understand what is going on during diabetes we need to understand how the eye is structured. The eye is unique in a number of ways. It is one of the most metabolically active tissues in the body. While most of our body is shielded from solar radiation, the eye focuses it and must constantly replace the damaged bits. The visible wave lengths of this radiation are, of course, the signal that the eye was designed to “see”. Given this one would expect that the detectors (rods and cones) would be placed right at the focal point where the light is concentrated – sort of like how your satellite TV dish is set up. Instead, things are quite a bit more complicated. The problem that causes this complexity is all of that metabolic activity. Photoreceptors do a LOT of work to process those photons and need access to glucose. In fact our photoreceptors have so much to do that they need assistants. Those assistants are called Retinal Pigment Epithelial cells and we will abbreviate this tissue RPE. One of the things that the RPE does is to recycle the compounds that are used up during the process of detecting photons. Photoreceptors are constantly shedding their detectors and growing new ones (remember, solar radiation causes damage and they need to constantly renew the damaged bits) and the RPE gobble up these shed pieces and reprocess them as well. Now the blood supply is at the very back of the eye. We call this tissue that contains the blood vessels the Choroid. The RPE sit right next to the Choroid and take up all the nutrients. They pass these nutrients on to the photoreceptors. This arrangement makes the most sense since if the blood vessels and the RPE were in front of the photoreceptors they would really screw up the light path. Unfortunately, we still have a ton of neural circuitry that needs to get placed somewhere. It sits in front of the photoreceptors (there is no more room behind). Apparently, during evolution, creatures that processed the visual signal immediately (before it was transported back to the brain) had a survival advantage since they could avoid predators and strike prey more quickly. Presumably it is for this reason that we have several layers of neurons between the photoreceptors and the light.
It always seemed to me to be a weird arrangement but during the process of writing this book chapter I came across and interesting find. The retina is really part of the brain and just like the brain there are support cells called glia nestled in between the neurons. What I found out was that people had examined the optical properties of these glial cells (called Muller cells). The Muller cells stretch all the way from the outer part of the retina where the light hits it down to the photoreceptors. Amazingly, despite all of the stuff that needs to be present in the cell for that cell to live and function, these Muller cells are optically clear. In essence they function like optical cables sending the light safely down past all of those irregularly shaped cell bodies that would bounce the light in crazy ways from the surface of the retina to the photoreceptors such that each photon retains its relationship to the photon next to it.
To recap, the most important point to remember is that the photoreceptors are at the very back of the eye and that they are VERY hungry all the time. The RPE sits between the photoreceptors and their food source – the blood vessels. In my next post (which I promise will be this week) I will describe how diabetes screws this up.
