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An in vitro cell model to study microglia activation in diabetic retinopathy
Hai Xie1,2, Chaoyang Zhang3,4,5, Jingting Zhang3,4,5
1Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
Abstract:
Microglial activation has been studied extensively in diabetic retinopathy. We have previously detected activation and migration of microglia in 8-week-old diabetic rat retinas. It is widely acknowledged that microglia-mediated inflammation contributes to the progression of diabetic retinopathy. However, existing cell models do not explore the role of activated microglia in vitro. In this study, microglia were subject to various conditions mimicking diabetic retinopathy, including high glucose, glyoxal, and hypoxia. Under high glucose or glyoxal treatment, microglia demonstrated only partially functional changes, while under hypoxia, microglia became fully activated showing enlarged cell bodies, enhanced migration and phagocytosis as well as increased production of pro-inflammatory factors such as cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS). The data indicate that hypoxia-treated microglia is an optimal in vitro model for exploration of microglia activation in diabetic retinopathy.
Insights
Hypoxia fully activates microglia, mimicking diabetic retinopathy in vitro. This finding establishes a superior cell model for studying microglial activation and inflammation in diabetic eye disease.
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Microglial activation is implicated in diabetic retinopathy progression.
- Previous studies detected microglial activation and migration in diabetic rat retinas.
- Current in vitro models do not fully replicate activated microglia in diabetic retinopathy.
Purpose of the Study:
- To establish an optimal in vitro model for studying microglia activation in diabetic retinopathy.
- To investigate the effects of conditions mimicking diabetic retinopathy on microglia.
Main Methods:
- Microglia were exposed to high glucose, glyoxal, and hypoxia.
- Functional changes, cell morphology, migration, phagocytosis, and pro-inflammatory factor production were assessed.
Main Results:
- High glucose or glyoxal induced only partial functional changes in microglia.
- Hypoxia led to full microglial activation, including enlarged cell bodies, enhanced migration and phagocytosis.
- Hypoxia increased the production of pro-inflammatory factors: cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS).
Conclusions:
- Hypoxia is the most effective condition for activating microglia in vitro to mimic diabetic retinopathy.
- Hypoxia-treated microglia represent an optimal model for exploring microglial activation in diabetic retinopathy.
