Article

Review Calls for Therapies to Curb Diabetic Retinopathy Prior to Vascular Symptoms

A new review article says neuroinflammation and oxidative stress appear to act together to weaken the diabetic retina and optic nerve; the authors say these insights could someday lead to better therapies to prevent diabetic retinopathy.

Neuroinflammation and oxidative stress might act together on the pathway toward diabetic retinopathy, and understanding that relationship could someday prove important for the development of therapies to prevent or treat the condition, according to a new a new review article.

The report, published in Neural Degeneration Research, is based mostly on studies conducted after 2014.

Globally, diabetes currently affects an estimated 425 million people, or 8.8% of the world’s adult population between the ages of 20 and 79. However, within the next 25 years, projections indicate that the total patient load could be as high as 629 million, writes corresponding author Ana Maria Blanco Martinez, PhD, of the Federal University of Rio de Janeiro, in Brazil, and colleagues.

Roughly one-third of patients with diabetes also suffer from some form of diabetic retinopathy (DR), which is also the leading cause of blindness in adults aged 20-69. However, by the time a patient has been diabetic for 20 years, the patient has a 90% chance of experiencing DR.

Martinez and colleagues note that the primary focus of DR research has typically been built around the premise that hyperglycemia in patients with diabetes leads to vascular damage in the retina, which in turn results in loss of vision. Thus, therapies tend to be limited to a vascular scope.

“Even the current treatments available target only vascular changes,” Martinez and colleagues write. “However, there is now a great amount of evidence showing that the retina undergoes several changes even before the onset of clinically detectable DR.”

For instance, the researchers note that, “electrophysiological studies in humans have shown that after two years of diabetes the sensitivity to contrast and color is affected.”

Vascular changes are also preceded by other changes, such as morphological disturbances in neurons and glial cell types.

Diabetes affects the optic nerve, too. Patients with poor glycemic control have long been known to suffer from optic disc inflammation and edema. Indeed, visual conduction delay has been identified in patients within the first year of diabetes.

In the new review, Martinez and her research team outline how inflammation and oxidative stress appear to be active both before and during the vascular-symptom phase of DR.

Of particular importance seems to be the multivalent lectin galectin-3. They write that neuroinflammation and galectin-3 mediate neurodegeneration in the diabetic visual system, hypothesizing that the “hyperglycemic state increases advanced glycation end product (AGE) and reactive oxygen species (ROS) production, activating microglia/macrophage expression of gal-3 and other pro-inflammatory cytokines through nuclear factor-kappa B (NFkB) activation.”

The authors argue that new therapeutic strategies are needed in order to prevent DR even before the vascular symptoms appear. They note, however, that early attempts to develop therapies based on the research contained in the review article have generally been unsuccessful or inconclusive.

“Therefore, further studies on the early pathological processes of the DR, such as neuroinflammation-related oxidative stress, are needed so that new effective therapeutic approaches are created,” they say. Those studies should give considerable attention to galectin-3, Martinez and colleagues say, because fully understanding how it works could prove pivotal in elucidating the mechanisms behind DR.

Reference

Mendonca HR, Carpi-Santos R, da Costa Calaza K, Blanco Martinez AM. Neuroinflammation and oxidative stress act in concert to promote neurodegeneration in the diabetic retina and optic nerve: galectin-3 participation. Neural Regen Res 2020;15:625-35.

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