Age-related macular degeneration (AMD), one of the leading causes of
blindness worldwide, causes personal suffering and high socioeconomic costs. While there has been progress in the treatments for the neovascular form of AMD, no
therapy is yet available for the more common dry form, also known as
geographic atrophy. We analysed the
retinal tissue in a mouse model of
retinal degeneration caused by
sodium iodate (NaIO3)-induced retinal pigment epithelium (RPE)
atrophy to understand the underlying pathology.
RNA sequencing (
RNA-seq), qRT-PCR, Western blot, immunohistochemistry of the retinas and multiplex ELISA of the mouse serum were applied to find the pathways involved in the degeneration.
NaIO3 caused patchy RPE loss and thinning of the photoreceptor layer. This was accompanied by the increased
retinal expression of
complement components c1s, c3, c4, cfb and cfh. C1s, C3, CFH and CFB were
complement proteins, with enhanced deposition at day 3. C4 was upregulated in
retinal degeneration at day 10. Consistently, the transcript levels of proinflammatory ccl-2, -3, -5, il-1β,
il-33 and tgf-β were increased in the retinas of
NaIO3 mice, but
vegf-a mRNA was reduced. Macrophages, microglia and gliotic Müller cells could be a cellular source for local
retinal inflammatory changes in the
NaIO3 retina. Systemic
complement and
cytokines/
chemokines remained unaltered in this model of NaIO3-dependent
retinal degeneration. In conclusion, systemically administered
NaIO3 promotes degenerative and inflammatory processes in the retina, which can mimic the hallmarks of
geographic atrophy.