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Updated: Feb 24, 2026
Long-Term, Serum-Free Cultivation of Organotypic Mouse Retina Explants with Intact Retinal Pigment Epithelium
Published on: November 25, 2020
E2f1 mediates high glucose-induced neuronal death in cultured mouse retinal explants
Yujiao Wang1, Yi Zhou1, Lirong Xiao1
1a Department of Ophthalmology, Research Laboratory of Ophthalmology and Vision Sciences , Torsten-Wiesel Research Institute of World Eye Organization, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu , China.
Insights
High glucose damages retinal neurons and Müller glial cells, causing cell death and abnormal division. E2f1 gene inactivation protects neurons but not glial cells or blood vessels from these effects.
Area of Science:
- Ophthalmology
- Cell Biology
- Diabetology
Background:
- Diabetic retinopathy (DR) is a leading cause of blindness globally.
- Hyperglycemia is a key risk factor, but underlying mechanisms of DR and diabetic retinopathy of prematurity (ROP) are unclear.
- Understanding high glucose effects on retinal cells is crucial.
Purpose of the Study:
- To investigate the molecular and cellular effects of high glucose on mouse retinal explants.
- To explore the role of E2f1 in high glucose-induced retinal changes.
- To elucidate mechanisms of diabetic retinopathy and diabetic ROP.
Main Methods:
- Cultured wild type and E2f1-/- mouse retinal explants (postnatal day 8).
- Exposed explants to normal glucose, high osmotic, or high glucose media.
- Used cobalt chloride (CoCl2) to mimic hypoxia.
Main Results:
- High glucose induced cell death and ectopic division in retinal neurons (ganglion, bipolar cells).
- Müller glial cells underwent cell cycle re-entry with altered morphology and migration.
- High glucose inhibited hyperoxia-induced blood vessel regression.
- E2f1 inactivation rescued neuronal cell death and ectopic division, but not glial or vascular changes.
Conclusions:
- High glucose exerts distinct effects on retinal neurons, glial cells, and blood vessels.
- E2f1 mediates high glucose effects on retinal neurons.
- Findings offer insights into DR and diabetic ROP mechanisms and suggest therapeutic targets.
Abstract:
Diabetic retinopathy (DR) is the most common complication of diabetes and remains one of the major causes of blindness in the world; infants born to diabetic mothers have higher risk of developing retinopathy of prematurity (ROP). While hyperglycemia is a major risk factor, the molecular and cellular mechanisms underlying DR and diabetic ROP are poorly understood. To explore the consequences of retinal cells under high glucose, we cultured wild type or E2f1-/- mouse retinal explants from postnatal day 8 with normal glucose, high osmotic or high glucose media. Explants were also incubated with cobalt chloride (CoCl2) to mimic the hypoxic condition. We showed that, at 7 days post exposure to high glucose, retinal explants displayed elevated cell death, ectopic cell division and intact retinal vascular plexus. Cell death mainly occurred in excitatory neurons, such as ganglion and bipolar cells, which were also ectopically dividing. Many Müller glial cells reentered the cell cycle; some had irregular morphology or migrated to other layers. High glucose inhibited the hyperoxia-induced blood vessel regression of retinal explants. Moreover, inactivation of E2f1 rescued high glucose-induced ectopic division and cell death of retinal neurons, but not ectopic cell division of Müller glial cells and vascular phenotypes. This suggests that high glucose has direct but distinct effects on retinal neurons, glial cells and blood vessels, and that E2f1 mediates its effects on retinal neurons. These findings shed new light onto mechanisms of DR and the fetal retinal abnormalities associated with maternal diabetes, and suggest possible new therapeutic strategies.
