Could diabetic retinopathy be an autoimmune disease?

Diabetic retinopathy is a common and progressive complication of diabetes mellitus. It is characterized by the loss of pericytes, hypertrophy of basement membrane, microaneurysms formation, increased vascular permeability, capillary occlusions, neovascularisation and fibrovascular proliferation. The pathogenesis of diabetic retinopathy is still insufficiently understood, although some reports have implicated the role of the immune system. We hypothesize that, according to some current data diabetic retinopathy could also be considered as an autoimmune disease. The finding of antipericyte and antiendothelial cell autoantibodies in the circulation of diabetic patients strongly suggests that some autoimmune activity has been involved in the early pathophysiology of diabetic retinopathy. There is even more evidence that implicates the presence of autoimmune mechanisms in the proliferative stage of this disease: elevated levels of tumor necrosis factor-alpha, interleukin-8 and soluble interleukin-2 receptor in the serum of diabetic patients, increased vitreous concentration of the interleukin-6 and interleukin-8 in patients with proliferative retinopathy. Furthermore, preretinal membranes in diabetic patients contain deposits of immunoglobulins, activated complement components, monocytes, T and B lymphocytes, fibroblastes and lymphokynes. In diabetic patients human leukocyte antigen DR and DQ expression on the retinal vascular endothelial cells as well as on pigment and nonpigment epithelial cells was found. These antigens are normally restricted to immunocompetent cells and play an important regulatory role in the immune response. Their aberrant expression has been found on nonlymphoid cells in various autoimmune diseases whilst abnormal expression of DR and DQ antigens at sites where they do not normally exist would result in autoimmunity by converting the target cell into a functional antigen-presenting cell. In conclusion, although the pathogenesis of diabetic retinopathy is not completely understood it is known that the immune system is certainly involved in its development. However, there is increasing evidence of the presence of some autoimmune processes in the early stages of diabetic retinopathy and particularly in its proliferative phases. Consequently, diabetic retinopathy could also be considered as an autoimmune disease.