Epigenetic modifications and potential new treatment targets in diabetic retinopathy
Lorena Perrone1, Carmela Matrone2, Lalit P Singh3
1EA 7281 R2D2, Medical School, Auvergne University, 63000 Clermont-Ferrand, France.
Abstract:
Retinopathy is a debilitating vascular complication of diabetes. As with other diabetic complications, diabetic retinopathy (DR) is characterized by the metabolic memory, which has been observed both in DR patients and in DR animal models. Evidences have provided that after a period of poor glucose control insulin or diabetes drug treatment fails to prevent the development and progression of DR even when good glycemic control is reinstituted (glucose normalization), suggesting a metabolic memory phenomenon. Recent studies also underline the role of epigenetic chromatin modifications as mediators of the metabolic memory. Indeed, epigenetic changes may lead to stable modification of gene expression, participating in DR pathogenesis. Moreover, increasing evidences suggest that environmental factors such as chronic hyperglycemia are implicated DR progression and may also affect the epigenetic state. Here we review recent findings demonstrating the key role of epigenetics in the progression of DR. Further elucidation of epigenetic mechanisms, acting both at the cis- and trans-chromatin structural elements, will yield new insights into the pathogenesis of DR and will open the way for the discovery of novel therapeutic targets to prevent DR progression.
Insights
Diabetic retinopathy (DR) exhibits metabolic memory, where prior poor glucose control impacts future outcomes. Epigenetic modifications are key mediators, offering new therapeutic targets for DR prevention.
Area of Science:
- Ophthalmology
- Endocrinology
- Genetics
Background:
- Diabetic retinopathy (DR) is a severe vascular complication of diabetes.
- DR is characterized by metabolic memory, persisting even after glycemic control is restored.
- Epigenetic chromatin modifications are increasingly recognized as mediators of this metabolic memory.
Purpose of the Study:
- To review recent findings on the role of epigenetics in DR progression.
- To highlight epigenetic mechanisms influencing DR pathogenesis.
- To identify novel therapeutic targets for preventing DR progression.
Main Methods:
- Review of recent scientific literature on epigenetics and diabetic retinopathy.
- Analysis of studies investigating epigenetic modifications in DR patients and animal models.
- Examination of the impact of hyperglycemia on epigenetic states.
Main Results:
- Epigenetic changes, including chromatin modifications, play a crucial role in DR pathogenesis.
- Environmental factors like chronic hyperglycemia can alter the epigenetic state, influencing DR progression.
- Epigenetic mechanisms acting on chromatin structure are central to understanding DR.
Conclusions:
- Epigenetics is fundamental to the pathogenesis and progression of diabetic retinopathy.
- Understanding cis- and trans-chromatin modifications offers new insights into DR.
- Elucidation of epigenetic pathways may lead to novel therapeutic strategies for DR.
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