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[Outlook for the future in the treatment of diabetic retinopathy]
B Vialettes1, P Silvestre-Aillaud, C Atlan-Gepner
1Service de Nutrition, Maladies Métaboliques et Endocrinologie, CHU Timone, Marseille, France.
Abstract:
With regard to diabetic retinopathy, in addition to the demonstration by the DCCT study that prevention is achieved by good metabolic control, our present knowledge on physiopathology leads us to imagine three types of possible therapeutic approach; inhibition of glucotoxicity, improvement of capillary flow, blockade of angiogenesis. 1) Inhibition of glucotoxicity Aldose reductase inhibitors can prevent cataract in diabetic or galactosemic rats. The effect of these drugs on retinopathy, evaluated in some clinical trials, remains controversial, suggesting a minor role. Aminoguanidine is an inhibitor of formation of advanced glycosylation end-products (AGE). This compound has been tested on a model of experimental retinopathy in rats. Parallel to the AGE decrease in retina, formation of microaneurysms and loss of endothelial cells in capillaries were delayed. Clinical tolerance allows human application and randomised trials will give further information on this potentially efficient drug. 2) Improvement of capillary flow This objective can be obtained by drugs inhibiting platelet aggregation or improving erythrocyte or leucocyte deformability. Clinical trials using such compounds were not very conclusive. 3) Blockade of angiogenesis Proliferation of new vessels is a rather severe stage of diabetic retinopathy. Angiogenesis is due to factors locally produced (as FGF, TGF and u-PA produced by anoxic tissues), systemic (IGF-1) or released by inflammatory reaction (IL1, TNF alpha and beta). One imagines usage of drugs which inhibit these factors and prevent angiogenesis. At the present time, two approaches have been used in proliferative retinopathy worsening despite panphotocoagulation; analogues of somatostatin and interferon alpha. The promissing results of these pilot studies have to be confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Diabetic retinopathy treatment explores inhibiting glucotoxicity, improving capillary flow, and blocking angiogenesis. Aminoguanidine shows promise in delaying retinopathy progression by inhibiting advanced glycosylation end-products.
Area of Science:
- Ophthalmology
- Endocrinology
- Pharmacology
Context:
- Diabetic retinopathy is a leading cause of vision loss in diabetic patients.
- Current understanding of diabetic retinopathy pathophysiology suggests multiple therapeutic targets.
- Good metabolic control is crucial for preventing diabetic retinopathy, as shown by the DCCT study.
Purpose:
- To explore potential therapeutic strategies for diabetic retinopathy based on its pathophysiology.
- To evaluate the efficacy of inhibiting glucotoxicity, improving capillary flow, and blocking angiogenesis.
- To assess the role of aminoguanidine in preventing diabetic retinopathy progression.
Summary:
- Inhibition of glucotoxicity: Aldose reductase inhibitors have shown limited efficacy, while aminoguanidine, an inhibitor of advanced glycosylation end-products (AGEs), demonstrated potential in delaying microaneurysm formation and endothelial cell loss in experimental models.
- Improvement of capillary flow: Drugs targeting platelet aggregation or red/white blood cell deformability have yielded inconclusive results in clinical trials.
- Blockade of angiogenesis: For proliferative retinopathy, therapies targeting angiogenesis, such as somatostatin analogues and interferon alpha, show promise but require further confirmation.
Impact:
- Identifies promising therapeutic avenues for diabetic retinopathy, including AGE inhibition and anti-angiogenic strategies.
- Highlights the need for further clinical trials to validate the efficacy of novel therapeutic agents.
- Provides insights into the complex pathophysiology of diabetic retinopathy and potential interventions.