Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation in mice

Proceedings of the National Academy of Sciences of the United States of America
Michael LandowskiCatherine Bowes Rickman

Abstract

One of the strongest susceptibility genes for age-related macular degeneration (AMD) is complement factor H (CFH); however, its impact on AMD pathobiology remains unresolved. Here, the effect of the principal AMD-risk-associated CFH variant (Y402H) on the development and progression of age-dependent AMD-like pathologies was determined in vivo. Transgenic mice expressing equal amounts of the full-length normal human CFH Y402 (CFH-Y/0) or the AMD-risk associated CFH H402 (CFH-H/H) variant on a Cfh -/- background were aged to 90 weeks and switched from normal diet (ND) to a high fat, cholesterol-enriched (HFC) diet for 8 weeks. The resulting phenotype was compared with age-matched controls maintained on ND. Remarkably, an AMD-like phenotype consisting of vision loss, increased retinal pigmented epithelium (RPE) stress, and increased basal laminar deposits was detected only in aged CFH-H/H mice following the HFC diet. These changes were not observed in aged CFH-Y/0 mice or in younger (36- to 40-week-old) CFH mice of both genotypes fed either diet. Biochemical analyses of aged CFH mice after HFC diet revealed genotype-dependent changes in plasma and eyecup lipoproteins, but not complement activation, which correlated with the AMD-l...Continue Reading

References

Apr 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·D T Fearon
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·A K Sharma, M K Pangburn
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Sep 5, 2002·American Journal of Ophthalmology·Don H AndersonLincoln V Johnson
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·John W CrabbJoe G Hollyfield
May 28, 2004·Molecular Immunology·Santiago Rodríguez de CórdobaPilar Sánchez-Corral
Jul 28, 2004·Investigative Ophthalmology & Visual Science·Nataliya GordiyenkoIgnacio R Rodriguez
Jan 18, 2005·Journal of Lipid Research·Chuan-Ming LiChristine A Curcio
Mar 12, 2005·Science·Jonathan L HainesMargaret A Pericak-Vance
Mar 12, 2005·Science·Albert O EdwardsLindsay A Farrer
Mar 12, 2005·Science·Robert J KleinJosephine Hoh
May 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·Gregory S HagemanRando Allikmets
Aug 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·G MalekC Bowes Rickman
Aug 29, 2006·Investigative Ophthalmology & Visual Science·Md Nawajes A Mandal, Radha Ayyagari
Apr 3, 2007·Molecular Immunology·Christine SkerkaPeter F Zipfel
Feb 12, 2008·Investigative Ophthalmology & Visual Science·Rebecca J OrmsbyDavid L Gordon
Jul 4, 2008·PloS One·Hendrik P N SchollMartin Oppermann
Sep 23, 2008·Investigative Ophthalmology & Visual Science·Lan WangChristine A Curcio
May 20, 2009·Experimental Eye Research·Masashi FujiharaJames T Handa
Aug 8, 2009·Investigative Ophthalmology & Visual Science·Robyn ReynoldsJohanna M Seddon
Sep 5, 2009·Nature Reviews. Immunology·Peter F Zipfel, Christine Skerka
Dec 8, 2009·Progress in Retinal and Eye Research·Don H AndersonLincoln V Johnson
Dec 17, 2009·Methods in Molecular Biology·Sampath ParthasarathyNalini Santanam
Mar 6, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rolf HerrmannVadim Y Arshavsky
Jun 12, 2010·Investigative Ophthalmology & Visual Science·Rafael L Ufret-VincentyWojciech Kedzierski
Sep 15, 2010·Cell and Tissue Research·J Vidya Sarma, Peter A Ward
Sep 30, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Una KellyCatherine Bowes Rickman
Jun 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jin-Dong DingCatherine Bowes Rickman
Sep 6, 2011·The British Journal of Ophthalmology·Christine A CurcioJiahn-Dar Huang
Oct 25, 2011·Nature Genetics·Soumya RaychaudhuriJohanna M Seddon
Aug 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Peter X ShawKang Zhang

❮ Previous
Next ❯

Citations

Mar 11, 2020·Cells·T J Hollingsworth, Alecia K Gross
Jul 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Young-Mi GoYan Chen
Aug 2, 2020·The Journal of Biological Chemistry·Una L KellyCatherine Bowes Rickman
Nov 13, 2019·Proceedings of the National Academy of Sciences of the United States of America·Khanh V DoNicolas G Bazan
Dec 22, 2019·International Journal of Molecular Sciences·Hee Young ChoNam Keun Kim
Dec 20, 2020·Experimental Eye Research·Sudha Priya Soundara PandiJessica L Teeling
Jan 15, 2021·Experimental Eye Research·Danielle A Clarkson-TownsendMachelle T Pardue
Feb 19, 2021·The FEBS Journal·Oluwaseun FatobaToshihide Yamashita
Feb 19, 2020·Free Radical Biology & Medicine·Sheldon RowanAllen Taylor
Feb 22, 2021·Progress in Retinal and Eye Research·Sarah de JongAnneke I den Hollander
Mar 23, 2021·Cellular and Molecular Life Sciences : CMLS·Angela ArmentoSimon J Clark
Mar 22, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gopalan GnanaguruPatricia A D'Amore
May 8, 2021·Nature Reviews. Disease Primers·Monika FleckensteinEmily Y Chew
May 20, 2021·Expert Review of Clinical Immunology·Mohammed OsmanChristian Pagnoux
May 28, 2021·The British Journal of Ophthalmology·Zhen Ji ChenLi Jia Chen
Jun 9, 2021·GeroScience·Ana P ValenciaDavid J Marcinek
Jul 3, 2021·Journal of Clinical Medicine·Enrique García-GenF Bosch-Morell
Aug 5, 2021·The New England Journal of Medicine·Rajendra S Apte
Aug 10, 2021·Journal of Immunology Research·Shuqi QinYanling Wang
Aug 17, 2021·Acta Medica Lituanica·Ho Hin Ma, Rasa Liutkevičienė
Nov 18, 2021·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Michael Landowski, Catherine Bowes Rickman

❮ Previous
Next ❯

Methods Mentioned

BETA
Transgenic
transmission electron microscopy
environmental stress
MDA
Protein Assay
Assay

Software Mentioned

OriginPro
ImageJ
OriginLab

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.