Related Experiment Video
Updated: Apr 16, 2026
Isolation of Retinal Pigment Epithelial Cells from Guinea Pig Eyes
Published on: May 9, 2023
7-Ketocholesterol increases retinal microglial migration, activation, and angiogenicity: a potential pathogenic
Maanasa Indaram1, Wenxin Ma1, Lian Zhao1
1Unit on Neuron-Glia Interactions in Retinal Disease, Laboratory of Retinal Cell and Molecular Biology, National Eye institute, National Institutes of Health, Bethesda, MD, USA.
Abstract:
Age-related macular degeneration (AMD) has been associated with both accumulation of lipid and lipid oxidative products, as well as increased neuroinflammatory changes and microglial activation in the outer retina. However, the relationships between these factors are incompletely understood. 7-Ketocholesterol (7KCh) is a cholesterol oxidation product localized to the outer retina with prominent pro-inflammatory effects. To explore the potential relationship between 7KCh and microglial activation, we localized 7KCh and microglia to the outer retina of aged mice and investigated 7KCh effects on retinal microglia in both in vitro and in vivo systems. We found that retinal microglia demonstrated a prominent chemotropism to 7KCh and readily internalized 7KCh. Sublethal concentrations of 7KCh resulted in microglial activation and polarization to a pro-inflammatory M1 state via NLRP3 inflammasome activation. Microglia exposed to 7KCh reduced expression of neurotrophic growth factors but increased expression of angiogenic factors, transitioning to a more neurotoxic and pro-angiogenic phenotype. Finally, subretinal transplantation of 7KCh-exposed microglia promoted choroidal neovascularization (CNV) relative to control microglia in a Matrigel-CNV model. The interaction of retinal microglia with 7KCh in the aged retina may thus underlie how outer retinal lipid accumulation in intermediate AMD results in neuroinflammation that ultimately drives progression towards advanced AMD.
Insights
Cholesterol oxidation product 7-ketocholesterol (7KCh) activates retinal microglia, promoting inflammation and potentially driving age-related macular degeneration (AMD) progression. This study links lipid accumulation in AMD to neuroinflammation and neovascularization.
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Age-related macular degeneration (AMD) involves lipid accumulation and neuroinflammation in the outer retina.
- The role of cholesterol oxidation products, like 7-ketocholesterol (7KCh), in microglial activation and AMD pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the relationship between 7-ketocholesterol (7KCh) and microglial activation in the aged retina.
- To explore the effects of 7KCh on retinal microglia in vitro and in vivo.
Main Methods:
- Localization of 7KCh and microglia in aged mouse retinas.
- In vitro and in vivo experiments assessing 7KCh effects on retinal microglia.
- Analysis of microglial activation state, gene expression, and function.
- Assessment of choroidal neovascularization (CNV) using a Matrigel model.
Main Results:
- Retinal microglia exhibited chemotropism towards and internalized 7KCh.
- 7KCh induced microglial activation and M1 polarization via NLRP3 inflammasome activation.
- 7KCh-exposed microglia showed reduced neurotrophic and increased angiogenic factor expression, adopting a neurotoxic, pro-angiogenic phenotype.
- Transplanted 7KCh-exposed microglia promoted CNV.
Conclusions:
- The interaction between retinal microglia and 7KCh may explain how lipid accumulation in intermediate AMD leads to neuroinflammation.
- This neuroinflammation, driven by 7KCh-induced microglial changes, may contribute to the progression of AMD towards advanced stages.
