Jeffery, G;
Sivapathasuntharam, C;
Hayes, M;
Shinhmar, H;
Hoh Kam, J;
Sivaprasad, S;
(2019)
Complement factor H regulates retinal development and its absence may establish a footprint for age related macular degeneration.
Scientific Reports
, 9
, Article 1082. 10.1038/s41598-018-37673-6.
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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.
| Type: | Article |
|---|---|
| Title: | Complement factor H regulates retinal development and its absence may establish a footprint for age related macular degeneration |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-018-37673-6 |
| Publisher version: | https://doi.org/10.1038/s41598-018-37673-6 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons .org/licenses/by/4.0/. |
| Keywords: | Immunity, retinal degeneration, ageing, mitochondria, retinal function |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10066742 |
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