What is diabetic retinopathy?
Diabetic retinopathy (DR) is a serious complication of diabetes mellitus that affects the eyes and is a leading cause of vision loss and blindness among working-age adults worldwide. It results from damage to the blood vessels of the retina, the light-sensitive tissue located at the back of the eye. Diabetic retinopathy can occur in individuals with either type 1 or type 2 diabetes and typically develops gradually over time.
There are two main types of diabetic retinopathy:
- Non-proliferative diabetic retinopathy (NPDR): In NPDR, the early stage of the disease, small blood vessels in the retina leak fluid or blood into the retina, causing it to swell or develop tiny hemorrhages. These changes may not cause noticeable symptoms initially, but they can be detected during a comprehensive eye examination. As NPDR progresses, the walls of the blood vessels may weaken and develop microaneurysms, leading to further leakage and ischemia (lack of blood flow) in the retina.
- Proliferative diabetic retinopathy (PDR): In PDR, the more advanced stage of the disease, new abnormal blood vessels (neovascularization) begin to grow on the surface of the retina or into the vitreous gel that fills the eye. These fragile new blood vessels are prone to leakage and can cause severe vision problems, including vitreous hemorrhage (bleeding into the vitreous), retinal detachment (separation of the retina from the back of the eye), and neovascular glaucoma (increased pressure inside the eye due to blockage of the drainage system). PDR can lead to severe vision loss or blindness if left untreated.
What is the relationship between DR and oxidative stress?
The relationship between diabetic retinopathy (DR) and oxidative stress is well-established and plays a significant role in the pathogenesis and progression of the disease. Oxidative stress occurs when there’s an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them with antioxidants.
Several factors contribute to oxidative stress in diabetic retinopathy:
- Hyperglycemia: Chronic hyperglycemia (high blood sugar levels) is a primary contributor to oxidative stress in diabetes. Elevated glucose levels can lead to increased production of ROS through various pathways, including glucose auto-oxidation, advanced glycation end products (AGEs) formation, and activation of protein kinase C (PKC). Excessive ROS production damages the delicate blood vessels (capillaries) in the retina, leading to microvascular complications such as retinal hemorrhages, microaneurysms, and capillary nonperfusion.
- Mitochondrial Dysfunction: Mitochondria are the primary source of ROS production in cells and play a crucial role in cellular energy metabolism. Dysfunction of mitochondria, such as impaired electron transport chain function or reduced antioxidant defenses, can lead to increased ROS generation and oxidative stress. Mitochondrial dysfunction is implicated in the pathogenesis of diabetic retinopathy and contributes to retinal cell damage and dysfunction.
- Inflammation: Chronic low-grade inflammation is a hallmark of diabetic retinopathy and contributes to oxidative stress. Inflammatory mediators, such as cytokines and chemokines, activate immune cells and stimulate the production of ROS as part of the immune response. In turn, ROS can further activate inflammatory signaling pathways, creating a positive feedback loop that exacerbates retinal tissue damage and inflammation.
- Vascular Dysfunction: Oxidative stress impairs endothelial function and contributes to endothelial dysfunction in the retinal blood vessels. Endothelial dysfunction is characterized by reduced nitric oxide (NO) bioavailability, increased production of vasoconstrictors, and enhanced expression of adhesion molecules. These changes promote vascular inflammation, leukocyte adhesion, and increased permeability of the blood-retinal barrier, leading to retinal edema and ischemia.
- Activation of Pro-fibrotic Pathways: Oxidative stress activates pro-fibrotic pathways in the retina, leading to the production of extracellular matrix proteins and fibrotic tissue remodeling. Fibrotic changes contribute to the development of tractional retinal detachment, a severe complication of proliferative diabetic retinopathy.
Overall, oxidative stress is a central mechanism underlying the development and progression of diabetic retinopathy by contributing to retinal vascular dysfunction, inflammation, endothelial dysfunction, and tissue damage.