Is diabetic retinopathy an inflammatory disease?
- Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston MA, 02114, USA; email@example.com
More work remains to prove this hypothesis
L ast year an ARVO symposium organised by Tim Kern was titled “Is diabetic retinopathy an inflammatory disease?” It is a timely question. chronic subclinical inflammation may underlie much of the vascular pathology of diabetic retinopathy. Nomenclature is critical to this discussion, so the definition of inflammation bears repeating here. Macroscopic inflammation comprises the classic signs of pain (dolor), heat (calor), redness (rubor), swelling (tumor), and loss of function (functio laesa).1 None of these signs, except for swelling and loss of function, clearly applies to diabetic retina. However, at a microscopic level, inflammation consists of vessel dilatation, altered flow, exudation of fluids, including plasma proteins, and leucocyte accumulation and migration.1 Given the recent data that have been generated in relevant models of diabetic retinopathy, the latter definition appears to fit. A brief overview of the evidence illustrates this point.
Within one week of experimental diabetes, leucocytes adhere to and accumulate within the vasculature of the retina.2,3 A subset of these leucocytes exit the vasculature and transmigrate into the neural retina.2,4 The leucocyte increases are moderate in nature and precede any overt clinical evidence of retinopathy. However, they progress with time.2 Monocytes and neutrophils predominate,4 although preliminary data suggest that lymphocytes may be involved as well (Ahmed, Ishida, Adamis, et al, unpublished observation). The leucocytes actively tether themselves to the endothelial cell lining via classic adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) on the vasculature2 and β2 integrins on the leucocytes.3 The expression levels for these adhesion molecules increase in early diabetes and correlate with the leucocyte increases.2,3 Additional adhesion molecules, including vascular cell adhesion molecule-1 (VCAM-1) and VLA-4 may also be involved, but here the …