Complement Receptor 1 (CR1/CD35)-expressing retinal pigment epithelial cells as a potential therapy for age-related macular degeneration

Ken T. Simmons, John L. Mazzilli, Stacey L. Mueller-Ortiz, Aleksey Y. Domozhirov, Charles A. Garcia, Eva M. Zsigmond, Rick A. Wetsel

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The purpose of this study was to identify a membrane-bound complement inhibitor that could be overexpressed on retinal pigment epithelial cells (RPE) providing a potential therapy for age-related macular degeneration (AMD). This type of therapy may allow replacement of damaged RPE with cells that are able to limit complement activation in the retina. Complement Receptor 1 (CR1) is a membrane-bound complement inhibitor commonly found on erythrocytes and immune cells. In this study, QPCR and flow cytometry data demonstrated that CR1 is not well-expressed by RPE, indicating that its overexpression may provide extra protection from complement activation. To screen CR1 for this ability, a stable CR1-expressing ARPE19 line was created using a combination of antibiotic selection and FACS. Cell-based assays were used to demonstrate that addition of CR1 inhibited deposition of complement proteins C3b and C6 on the transfected line. In the end, this study identifies CR1 as a complement inhibitor that may be overexpressed on stem cell-derived RPE to create a potential “enhanced” cell therapy for AMD. A combination cell/complement therapy may create transplantable RPE better suited to avoid complement-mediated lysis and limit chronic inflammation in the retina.

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalMolecular Immunology
Volume118
DOIs
StatePublished - Feb 2020
Externally publishedYes

Keywords

  • Age-related macular degeneration
  • CR1
  • Cell therapy
  • Complement
  • Retinal pigment epithelium

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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