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A model to study complement involvement in experimental retinal degeneration

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journal contribution
posted on 2018-02-13, 14:32 authored by Camilla Mohlin, Kerstin Sandholm, Anders Kvanta, Kristina N. Ekdahl, Kjell Johansson

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.

Funding

This study was supported by grants from the Carmen and Bertil Regnérs Foundation, Crown Princess Margaretas Committee for the Blind, Olle Engqvist Foundation, Sven and Dagmar Saléns Foundation, Ögonfonden (‘The Eye Foundation’), FORSS (Medical Research Council of Southeast Sweden), the faculty of Medical Sciences at Örebro University, faculty grants from the Linnaeus University, and by the Swedish Medical Research Council (VR) grant.

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