Autoimmune destruction of pericytes as the cause of diabetic retinopathy
1Faculty of Medicine, University of Otago, PO Box 913, Dunedin 9054, Dunedin, New Zealand. duncan.adams@stonebow.otago.ac.nz
Abstract:
In diabetic retinopathy, collapse of the retinal vasculature is associated with loss of the pericytes. These are contractile cells that together with endothelial cells form the terminal arterioles of the retina. The cause of the loss of pericytes is not known. Recently, it has been discovered that type 1 diabetes is caused by forbidden clones of cytotoxic T lymphocytes, which destroy the insulin-making cells with exquisite specificity. In the light of this, I postulate that an antigenically-related forbidden clone of cytotoxic T lymphocytes selectively destroys the pericytes and that this is the cause of the vascular collapse of diabetic retinopathy. If this is so, the therapeutic implications are immense, involving a switch from ineffectual tight glycemic control to immunotherapy. This is already used as immunosuppression to prevent organ transplant rejection, and as the immune ablation and autologous bone marrow cell reconstitution that has saved the lives of patients with lethally-severe scleroderma. Once the pericyte surface auto-antigen for the T lymphocytes has been isolated, selective destruction of the pathogenic T lymphocytes would be possible by manufacture and use of cytotoxic auto-antigen complexes, which arrests progression of the retinopathy.
Insights
Diabetic retinopathy may be caused by T lymphocytes attacking retinal pericytes. This suggests immunotherapy, not just glycemic control, could treat this vision-threatening complication.
Area of Science:
- Ophthalmology
- Immunology
- Endocrinology
Background:
- Diabetic retinopathy involves retinal vascular collapse linked to pericyte loss.
- The exact cause of pericyte loss in diabetic retinopathy remains unknown.
- Type 1 diabetes is linked to specific cytotoxic T lymphocytes targeting insulin-producing cells.
Purpose of the Study:
- To postulate a novel hypothesis for the etiology of diabetic retinopathy.
- To propose a new therapeutic strategy for managing diabetic retinopathy.
Main Methods:
- Review of existing literature on diabetic retinopathy and type 1 diabetes pathogenesis.
- Formulation of a hypothesis based on immunological principles and cellular interactions.
Main Results:
- A proposed mechanism where cytotoxic T lymphocytes, similar to those in type 1 diabetes, selectively destroy retinal pericytes.
- Identification of pericyte surface auto-antigen as a potential target for T lymphocytes.
Conclusions:
- The hypothesis suggests a potential autoimmune basis for diabetic retinopathy.
- Immunotherapy targeting pathogenic T lymphocytes offers a promising alternative or adjunct to glycemic control.
- Isolation of the auto-antigen could enable targeted therapies to halt retinopathy progression.
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