Complement Receptor 1 (CR1/CD35)-expressing retinal pigment epithelial cells as a potential therapy for age-related macular degeneration
| Autor: | Ken Simmons, Rick A. Wetsel, Charles A. Garcia, Stacey L. Mueller-Ortiz, John L. Mazzilli, Aleksey Y. Domozhirov, Eva M Zsigmond |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Erythrocytes Complement receptor 1 Immunology Inflammation Retinal Pigment Epithelium Retina Cell Line Cell therapy Macular Degeneration 03 medical and health sciences Complement inhibitor 0302 clinical medicine Immune system medicine Humans Complement Activation Molecular Biology Retinal pigment epithelium biology Chemistry Epithelial Cells eye diseases Complement C6 Cell biology Complement system 030104 developmental biology medicine.anatomical_structure Complement C3b Receptors Complement 3b sense organs biology.gene medicine.symptom Retinal Pigments 030215 immunology |
| Zdroj: | Molecular Immunology. 118:91-98 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/j.molimm.2019.11.007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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