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Updated: Mar 17, 2026
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Efficient Dissection and Culture of Primary Mouse Retinal Pigment Epithelial Cells
Published on: February 10, 2021
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Protective responses to sublytic complement in the retinal pigment epithelium
Li Xuan Tan1, Kimberly A Toops2, Aparna Lakkaraju3
1Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706; Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, WI 53706;
Summary
The retinal pigment epithelium (RPE) protects against complement attack via CD59 recycling and lysosome fusion. Cholesterol buildup impairs these defenses, leading to mitochondrial damage in macular degeneration.
Area of Science:
- Ophthalmology
- Cell Biology
- Immunology
Background:
- The retinal pigment epithelium (RPE) is vulnerable in macular degenerations.
- Complement system activation contributes to RPE injury.
- Mechanisms by which RPE combats complement attack are unclear.
Purpose of the Study:
- Investigate RPE mechanisms limiting complement-induced injury.
- Understand how these mechanisms are compromised in macular degeneration models.
Main Methods:
- Used polarized primary RPE and Abca4(-/-) Stargardt disease mouse model.
- Examined RPE responses to complement attack.
- Assessed mitochondrial health and organelle traffic.
Main Results:
- RPE employs CD59 recycling and lysosome exocytosis to limit membrane attack complex (MAC) formation and preserve mitochondrial health.
- Cholesterol accumulation inhibits these defenses by activating acid sphingomyelinase (ASMase).
- Defective defenses lead to mitochondrial fragmentation and oxidative stress in RPE.
Conclusions:
- Accelerated CD59 recycling and lysosome exocytosis are critical RPE safeguards against complement attack.
- Cholesterol-induced ASMase activation disrupts these safeguards, contributing to macular degeneration pathogenesis.
- Therapies targeting cholesterol efflux or ASMase may protect RPE and treat macular degenerations.
