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Updated: Jul 17, 2026
An Assay to Detect Protection of the Retinal Vasculature from Diabetes-Related Death in Mice
Published on: January 12, 2024
High glucose induces caspase-independent cell death in retinal neural cells
A R Santiago1, A J Cristóvão, P F Santos
1Center for Neuroscience and Cell Biology, Department of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal.
Abstract:
Diabetic retinopathy is a leading cause of blindness among adults in the western countries. It has been reported that neurodegeneration may occur in diabetic retinas, but the mechanisms underlying retinal cell death are poorly understood. We found that high glucose increased the number of cells with condensed nuclei and the number of TUNEL-positive cells, and caused an increase in the translocation of phosphatidylserine to the outer leaflet of the plasma membrane, indicating that high glucose induces apoptosis in cultured retinal neural cells. The activity of caspases did not increase in high glucose-treated cells, but apoptosis-inducing factor (AIF) levels decreased in the mitochondria and increased in the nucleus, indicating a translocation to the nucleus where it may cause DNA fragmentation. These results demonstrate that elevated glucose induces apoptosis in cultured retinal neural cells. The increase in apoptosis is not dependent on caspase activation, but is mediated through AIF release from the mitochondria.
Insights
High glucose levels induce apoptosis in retinal neural cells, a key factor in diabetic retinopathy. This cell death occurs via the apoptosis-inducing factor (AIF) pathway, independent of caspase activation.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Diabetic retinopathy is a significant cause of adult blindness.
- Mechanisms of retinal cell death in diabetes are not fully understood.
- Neurodegeneration is implicated in diabetic retinas.
Purpose of the Study:
- To investigate the mechanisms of high glucose-induced apoptosis in cultured retinal neural cells.
- To determine the role of caspases and apoptosis-inducing factor (AIF) in this process.
Main Methods:
- Cultured retinal neural cells were exposed to high glucose conditions.
- Apoptosis was assessed by examining nuclear condensation, TUNEL positivity, and phosphatidylserine translocation.
- Caspase activity and AIF localization (mitochondria vs. nucleus) were analyzed.
Main Results:
- High glucose exposure increased markers of apoptosis, including condensed nuclei and TUNEL-positive cells.
- Phosphatidylserine translocated to the outer plasma membrane, confirming apoptosis.
- Caspase activity did not increase, but AIF levels decreased in mitochondria and increased in the nucleus.
Conclusions:
- Elevated glucose induces apoptosis in cultured retinal neural cells.
- This apoptosis is mediated by the translocation of AIF from mitochondria to the nucleus.
- The process is independent of caspase activation.
