A model to study complement involvement in experimental retinal degeneration

Camilla  Mohlin; Kerstin  Sandholm; Anders  Kvanta; Kristina N.  Ekdahl; Kjell  Johansson

doi:10.1080/03009734.2018.1431744

Camilla Mohlin Linnaeus University Faculty of Health and Life Science, Linnaeus Center of Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden
Kerstin Sandholm Linnaeus University Faculty of Health and Life Science, Linnaeus Center of Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden
Anders Kvanta Department of Clinical Neuroscience, Section for Ophthalmology and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden
Kristina N. Ekdahl Linnaeus University Faculty of Health and Life Science, Linnaeus Center of Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden
Kjell Johansson School of Medical Sciences, Örebro University, Örebro, Sweden

DOI: https://doi.org/10.1080/03009734.2018.1431744

Keywords: AMD, complement system, ocular diseases, retina, RPE

Abstract

Background: The complement system (CS) plays a role in the pathogenesis of a number of ocular diseases, including diabetic retinopathy (DR), glaucoma, uveitis, and age-related macular degeneration (AMD). Given that many of the complex eye-related degenerative diseases have limited treatment opportunities, we aimed to mimic the in vivo retinal degenerative process by developing a relevant co-culture system.

Method and materials: The adult porcine retina was co-cultured with the spontaneously arising human retinal pigment epithelial cells-19 (ARPE-19).

Results: Inflammatory activity was found after culture and included migrating microglial cells, gliosis, cell death, and CS activation (demonstrated by a minor increase in the secreted anaphylotoxin C3a in co-culture). CS components, including C1q, C3, C4, soluble C5b-9, and the C5a receptor, were expressed in the retina and/or ARPE cells after culture. C1q, C3, and CS regulators such as C4 binding protein (C4BP), factor H (CFH), and factor I (CFI) were secreted after culture.

Discussion: Thus, our research indicates that this co-culturing system may be useful for investigations of the CS and its involvement in experimental neurodegenerative diseases.

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