Related Experiment Video
Updated: Jul 15, 2026
Alternate Immersion in Glucose to Produce Prolonged Hyperglycemia in Zebrafish
Published on: May 5, 2021
RAGE and Diaph1 deficiency affect retinal cytoarchitecture both in physiological and long-term hyperglycemic settings
1Department of Human Physiology and Pathophysiology, School of Medicine, University of Warmia and Mazury in Olsztyn, Warszawska 30, 10-085 Olsztyn, Poland.
Abstract:
Retinal complications in diabetes are a leading cause of vision loss in adults. Long-term hyperglycemia triggers molecular changes that damage retinal neuronal tissues and blood vessels, leading to degeneration, inflammation, and vision impairment. Studies show that the Receptor for Advanced Glycation End-Products (RAGE) and its cytosolic ligand, Diaph1 are both implicated in the pathogenesis of diabetic complications; however, their role in the development of retinal damage is not yet clear. We hypothesized that the deletion of either RAGE or Diaph1 would be beneficial and prevent or delay damage to the retinal structure in diabetes. Wild-type, RAGE and Diaph1 knockout mice were used in the study. The mice were randomly selected and divided into control and diabetic groups. Diabetes was induced with Streptozotocin injections, and six months after diabetes induction all mice were sacrificed, samples collected and processed for morphometric analysis. Our analysis revealed a reduction in retinal depth across all layers between control and diabetic samples. The effect of RAGE or Diaph1 deletion on retinal structure differed, indicating that both proteins may play independent if not interchangeable roles in retina function and structure, highlighting their potential role in the pathogenesis of diabetic retinal complications.
Insights
Diabetic retinopathy, a cause of vision loss, involves damage to retinal tissues. Deleting Receptor for Advanced Glycation End-Products (RAGE) or Diaph1 in mice showed distinct effects on retinal structure, suggesting independent roles in diabetic eye complications.
Area of Science:
- Ophthalmology
- Diabetology
- Molecular Biology
Background:
- Diabetic complications, including retinopathy, are a major cause of adult vision loss.
- Long-term hyperglycemia induces molecular changes damaging retinal neurons and vasculature.
- The roles of Receptor for Advanced Glycation End-Products (RAGE) and Diaph1 in diabetic retinal damage are not fully understood.
Purpose of the Study:
- To investigate the role of RAGE and Diaph1 in diabetic retinal pathogenesis.
- To determine if deleting RAGE or Diaph1 prevents or delays retinal structural damage in diabetes.
Main Methods:
- Utilized wild-type, RAGE knockout, and Diaph1 knockout mice.
- Induced diabetes using Streptozotocin injections.
- Performed morphometric analysis on retinal samples six months post-induction.
Main Results:
- Diabetes induction led to a reduction in retinal depth across all layers in control mice.
- Deletion of RAGE and Diaph1 had differential effects on retinal structure.
- These findings suggest independent, potentially interchangeable roles for RAGE and Diaph1 in retinal structure.
Conclusions:
- RAGE and Diaph1 are implicated in the pathogenesis of diabetic retinopathy.
- Targeting RAGE or Diaph1 may offer therapeutic strategies for diabetic eye complications.
- Further research is needed to elucidate the precise mechanisms of RAGE and Diaph1 in diabetic retinal damage.
