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Sci Rep. 2019 Jan 31;9(1):1082. doi: 10.1038/s41598-018-37673-6.

Complement factor H regulates retinal development and its absence may establish a footprint for age related macular degeneration.

Author information

1
University College London, Institute of Ophthalmology, London, EC1V9EL, UK.
2
University College London, Institute of Ophthalmology, London, EC1V9EL, UK. g.jeffery@ucl.ac.uk.

Abstract

Age related macular degeneration (AMD) is the most common blinding disease in those over 60 years. In 50% of cases it is associated with polymorphisms of complement factor H (FH), implicating immune vulnerability. But such individuals may exhibit abnormal outer retinal blood flow decades before disease initiation, suggesting an early disease footprint. FH is expressed in the retinal pigmented epithelium (RPE). During development the RPE is adjacent to the site of retinal mitosis and complex regulatory interactions occur between the relatively mature RPE and retinal neuronal precursors that control the cell cycle. Here we ask if the absence of FH from the RPE influences retinal development using a mouse CFH knockout (Cfh-/-) with an aged retinal degenerative phenotype. We reveal that from birth, these mice have significantly disrupted and delayed retinal development. However, once development is complete, their retinae appear relatively normal, although many photoreceptor and RPE mitochondria are abnormally large, suggesting dysfunction consistent with premature ATP decline in Cfh-/-. Total retinal mtDNA is also reduced and these deficits are associated shortly after with reduced retinal function. Cfh-/+ mice also show significant abnormal patterns of cell production but not as great as in Cfh-/-. These results reveal that not only is FH an important player in sculpting retinal development but also that the developmental abnormality in Cfh-/- likely establishes critical vulnerability for later aged retinal degeneration.

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