| Affiliation |
(AGL) Chairman, Department of Ophthalmology, The Methodist Hospital, Houston, Texas; Professor of Ophthalmology, Weill Cornell Medicine, New York City, New York; (JY) Class of 2021, Baylor College of Medicine, Houston, Texas |
| Transcript |
Talk about diabetes in relation to the neuro-ophthalmic system. The first thing is you should know that diabetes means "like honey", and the reason is because your blood and your urine tastes sweet. Diabetes, of course, produces high sugar, and it is that hyperglycemia, the high sugar in your blood, that leads to glycation of lipids and proteins. And it is that glycation that is an abnormal process in contrast to glycosylation, which is the normal enzymatic way that your body creates glycolipids and glycoproteins. Glycation is an abnormal process that results in the production of advanced glycated end products (AGEs). These AGEs can bind onto receptors for the advanced glycated end products and it is these receptors for the AGE that converts AGE to RAGE. It is that RAGE that produces the signaling mechanisms that result in the problems that we see in diabetes both through a "kill yourself" pathway, a suicide pathway, called apoptosis, and a homicide pathway where cells are killed or damaged usually from inflammatory mediators and reactive oxygen intermediates, that are free radicals, that are destructive. The target of course is the pericyte. "Peri" means around and the cell, the site that it is around, is the endothelial cell. The pericyte is the target of the hyperglycemic induced attack, and it is this poor pericyte that suffers the damage. And when that occurs, the endothelial cell in the blood vessel doesn't work properly. That leads to leakage because of the breakdown of the blood retinal barrier and in the retina, that is what produces the destructive ophthalmoscopic findings of hemorrhage, exudate, and subretinal fluid. That is what we call the non-proliferative form of diabetic retinopathy However, over time, the progressive damage leads to ischemia, and that ischemia is manifesting as microaneurysms and small vessel disease in the retina. The ischemic retina then produces vascular endothelial growth factor (VEGF), and when that occurs, new vessels form and that is the form of diabetes that we call the proliferative form of diabetic retinopathy. So really this hyperglycemia leading to AGE and then RAGE changes the signaling mechanisms that leads to pericyte destruction and loss followed by breakdown of blood retinal barrier, leakage, ischemia, production of vascular endothelial growth factor, neovascularization, and proliferative diabetic retinopathy. So for neuro-op, the reason these things are important is: when we have the blood vessel supply to the nerve itself, the vaso nervorum, that nerve supply from the blood vessel tends to affect the core of the nerve as opposed to compressive lesions, like masses or aneurysms, that press on the nerve from the outside, that can damage the pupil fiber in a third nerve. So in the diabetic third where we have all the process that we've just described causing the small vessel ischemia at the vaso nervorum that tends to spare the pupil in the third nerve palsy, whereas the compressive lesion presses on the outside of the nerve and that tends to involve the pupil. So as a rule of thumb, a diabetic third normally spares the pupil and a compressive palsy normally causes pupil involvement. So if you understand the basics of this hyperglycemia then you can understand how diabetes causes eye disease. |
