Abstract
Purpose :
The complement system has been implicated in age related macular degeneration. RPE damageand subsequent photoreceptor cell degeneration induced by sodium iodatemay mimic dry AMD-like pathologies. Therefore, we investigated the role of C5 in this model using wild type and C5 knockout (KO) rats.
Methods :
Wild type and C5 KO rats (Regeneron Pharmaceuticals Inc.) were used in this study. Sodium iodate (25 mg/Kg) was given by an intravenous injection to induce retinal pigment epithelium (RPE) damage in rats. Infrared imageing (IR) and Optical coherence tomography (OCT) were used to assess in vivo RPE damage and photoreceptor cell degeneration on days -1, 1, 3, 7 and 14. OCT images were scored masked according to an OCT scoring system established in the lab. All animals were euthanized on day 14. RPE/Choroid was flat mounted and stained with RPE65 and ZO-1 antibody. Eye sections were used for histology and immunostaining for RPE65, cone/rhodopsin and Iba1. Data was analyzed by multiple t test.
Results :
Intravenous injection of sodium iodate at 25 mg/kg successfully induced RPE/retina damage and cell infiltration evidenced by OCT imaging. Compared to wild type controls, there were significantly higher OCT score and more dark/patchy dots in C5 KO rats at day 7 (p<0.05) and 14 (p<0.01) on montaged IR and OCT images. This was further evident by the loss of RPE65 staining and RPE cell morphological changes by ZO-1 staining in RPE/Choroid flat mount. Eye cup sections also showed more photoreceptor cell degeneration (cone/rhodopsin staining) and RPE cell damage (RPE65 staining), microglia activation (Iba1 staining) in C5 KO rats.
Conclusions :
Our results show that genetic deletion of complement C5 is not sufficient to block the development of RPE damage as seen in dry AMD-like pathologies in this sodium iodatemodel.
This is a 2020 ARVO Annual Meeting abstract.