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Chrishne Sivapathasuntharam, Matthew Hayes, Harpreet Shinhmar, Jaimie Hoh Kam, Sobha Sivaprasad, Glen Jeffery; Might retinal degeneration in the CFH-/- mouse have a developmental footprint?. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5240.
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© ARVO (1962-2015); The Authors (2016-present)
AMD is linked in 50% of cases to polymorphisms of CFH. But some young individuals with polymorphisms have deficits in choroidal blood flow before disease presents (Told,et al.2013). Further, complement is critical in refining neuronal connections (Stephan,et al.2012) in development and impacts on mitochondrial function. Here we ask if complement dysfunction in the retina might have a developmental footprint in a murine model.
We examine mitochondria in young (3 and 8 weeks) CFH-/- and C57 mice with EM (N=5 per group). Relative retinal mtDNA content was measured by spectrophotometry (N=4 per group). We also undertake scotopic ERG recordings of retinal function (N=5 per group). The CFH-/- is on a C57 background.
Retinal mitochondria in both the neural retina and RPE of CFH-/- mice show abnormalities at 3 weeks when the retina has achieved its adult architectural configuration. Many mitochondria are enlarged in both the retina and RPE. Enlarge mitochondria in photoreceptors are commonly located distally in the inner segment. Giant mitochondria are associated with senescence and reduced fission. They are also associated with reduced mtDNA. Measurements of mtDNA at this stage confirmed a significant decline in the CFH-/- animals compared to the C57 animals. ERGs undertaken at 3 weeks in CFH-/- are similar in amplitude to those in C57 mice. However, at 8 weeks there are significant reductions in the magnitude of the b-wave in CFH-/-.
CFH-/- mice have retinal abnormalities present from the time the retina adopts a mature form, although this does not translate immediately into a decline in retinal function. This may be due to the dysregulation of C3 during development in these animals which is key to signaling refinement on neuronal connections. Hence, AMD may have a youthful origin. It is also possible that the fine structure of the retina in CFH-/- deficient animals may be significantly different from normal because their refinement will not have been moderated by normal C3 expression which is regulated by CFH.Stephan, A.H., et al. 2012. Annu Rev Neurosci 35, 369-89.Told, R., et al. 2013. PLoS One 8(4), e60424.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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