Age-related Macular Degeneration and Modification of Systemic Complement Factor H Production Through Liver Transplantation

被引:37
作者
Khandhadia, Samir [1 ]
Hakobyan, Svetlana [2 ]
Heng, Ling Z. [3 ]
Gibson, Jane [1 ]
Adams, David H. [4 ,5 ]
Alexander, Graeme J. [6 ]
Gibson, Jonathan M. [7 ]
Martin, Keith R. [8 ,9 ]
Menon, Geeta [10 ]
Nash, Kathryn [11 ]
Sivaprasad, Sobha [12 ]
Ennis, Sarah [1 ]
Cree, Angela J. [1 ]
Morgan, B. Paul [2 ]
Lotery, Andrew J. [1 ]
机构
[1] Univ Southampton, Fac Med, Southampton SO16 6YD, Hants, England
[2] Cardiff Univ, Sch Med, Cardiff CF10 3AX, S Glam, Wales
[3] UCL, Inst Ophthalmol, London, England
[4] Univ Birmingham, Liver Res Ctr, Birmingham, W Midlands, England
[5] Univ Birmingham, NIHR Liver Biomed Res Unit, Birmingham, W Midlands, England
[6] Addenbrookes Hosp, Univ Dept Med, Cambridge, England
[7] Aston Univ, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England
[8] Univ Cambridge, Dept Ophthalmol, Cambridge, England
[9] Univ Cambridge, NIHR Biomed Res Ctr, Cambridge, England
[10] Frimley Pk Hosp NHS Fdn Trust, Frimley Pk, England
[11] Southampton Univ Hosp, Dept Hepatol, Southampton, Hants, England
[12] Kings Coll Hosp London, Dept Ophthalmol, London, England
基金
英国惠康基金;
关键词
HEMOLYTIC-UREMIC SYNDROME; POLYMORPHISM; RISK; MACULOPATHY; PROGRESSION; EXPRESSION; PROTEINS; Y402H;
D O I
10.1016/j.ophtha.2013.01.004
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: To investigate whether modification of liver complement factor H (CFH) production, by alteration of liver CFH Y402H genotype through liver transplantation (LT), influences the development of age-related macular degeneration (AMD). Design: Multicenter, cross-sectional study. Participants: We recruited 223 Western European patients >= 55 years old who had undergone LT >= 5 years previously. Methods: We determined AMD status using a standard grading system. Recipient CFH Y402H genotype was obtained from DNA extracted from recipient blood samples. Donor CFH Y402H genotype was inferred from recipient plasma CFH Y402H protein allotype, measured using enzyme-linked immunosorbent assays. This approach was verified by genotyping donor tissue from a subgroup of patients. Systemic complement activity was ascertained by measuring levels of plasma complement proteins using an enzyme-linked immunosorbent assay, including substrates (C3, C4), activation products (C3a, C4a, and terminal complement complex), and regulators (total CFH, C1 inhibitor). Main Outcome Measures: We evaluated AMD status and recipient and donor CFH Y402H genotype. Results: In LT patients, AMD was associated with recipient CFH Y402H genotype (P = 0.036; odds ratio [OR], 1.6; 95% confidence interval [CI], 1.0-2.4) but not with donor CFH Y402H genotype (P = 0.626), after controlling for age, sex, smoking status, and body mass index. Recipient plasma CFH Y402H protein allotype predicted donor CFH Y402H genotype with 100% accuracy (n = 49). Plasma complement protein or activation product levels were similar in LT patients with and without AMD. Compared with previously reported prevalence figures (Rotterdam Study), LT patients demonstrated a high prevalence of both AMD (64.6% vs 37.1%; OR, 3.09; P < 0.001) and the CFH Y402H sequence variation (41.9% vs 36.2%; OR, 1.27; P = 0.014). Conclusions: Presence of AMD is not associated with modification of hepatic CFH production. In addition, AMD is not associated with systemic complement activity in LT patients. These findings suggest that local intraocular complement activity is of greater importance in AMD pathogenesis. The high AMD prevalence observed in LT patients may be associated with the increased frequency of the CFH Y402H sequence variation. (C) 2013 by the American Academy of Ophthalmology.
引用
收藏
页码:1612 / 1618
页数:7
相关论文
共 32 条
  • [11] Therapeutic Effect of Oral Bisphosphonates on Choroidal Neovascularization in the Human Eye
    Honda, Shigeru
    Nagai, Takayuki
    Kondo, Naoshi
    Fukuda, Masahide
    Kusuhara, Sentaro
    Tsukahara, Yasutomo
    Negi, Akira
    [J]. JOURNAL OF OPHTHALMOLOGY, 2010, 2010
  • [12] The complement component C3a fragment is a potential biomarker for hepatitis C virus-related hepatocellular carcinoma
    Kanmura, Shuji
    Uto, Hirofumi
    Sato, Yuko
    Kumagai, Koutarou
    Sasaki, Fumisato
    Moriuchi, Akihiro
    Oketani, Makoto
    Ido, Akio
    Nagata, Kenji
    Hayashi, Katsuhiro
    Stuver, Sherri O.
    Tsubouchi, Hirohito
    [J]. JOURNAL OF GASTROENTEROLOGY, 2010, 45 (04) : 459 - 467
  • [13] A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss - AREDS Report No. 8
    Kassoff, A
    Kassoff, J
    Buehler, J
    Eglow, M
    Kaufman, F
    Mehu, M
    Kieval, S
    Mairs, M
    Graig, B
    Quattrocchi, A
    Jones, D
    Locatelli, J
    Ruby, A
    Capone, A
    Garretson, B
    Hassan, T
    Trese, MT
    Williams, GA
    Regan, V
    Manatrey, P
    Streasick, P
    Szydlowski, L
    McIver, F
    Bridges, C
    Stanley, C
    Cumming, K
    Lewis, B
    Zajechowski, M
    Margherio, RR
    Cox, MS
    Camille, J
    Falk, R
    Siedlak, P
    Neubert, C
    Klein, ML
    Stout, JT
    O'Malley, A
    Lauer, AK
    Robertson, JE
    Wilson, DJ
    Beardsley, C
    Anderson, H
    Wallace, P
    Smith, G
    Howard, S
    Dreyer, RF
    Ma, C
    Chenoweth, RG
    Zilis, JD
    Johnson, M
    [J]. ARCHIVES OF OPHTHALMOLOGY, 2001, 119 (10) : 1417 - 1436
  • [14] Age-related macular degeneration and the complement system
    Khandhadia, S.
    Cipriani, V.
    Yates, J. R. W.
    Lotery, A. J.
    [J]. IMMUNOBIOLOGY, 2012, 217 (02) : 127 - 146
  • [15] Klaver CCW, 2001, INVEST OPHTH VIS SCI, V42, P2237
  • [16] KLEIN R, 1992, OPHTHALMOLOGY, V99, P933
  • [17] Complement factor H polymorphism in age-related macular degeneration
    Klein, RJ
    Zeiss, C
    Chew, EY
    Tsai, JY
    Sackler, RS
    Haynes, C
    Henning, AK
    SanGiovanni, JP
    Mane, SM
    Mayne, ST
    Bracken, MB
    Ferris, FL
    Ott, J
    Barnstable, C
    Hoh, J
    [J]. SCIENCE, 2005, 308 (5720) : 385 - 389
  • [18] Role of Ocular Complement Factor H in a Murine Model of Choroidal Neovascularization
    Lyzogubov, Valeriy V.
    Tytarenko, Ruslana G.
    Jha, Purushottam
    Liu, Juan
    Bora, Nalini S.
    Bora, Puran S.
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2010, 177 (04) : 1870 - 1880
  • [19] Sparing of age-related macular degeneration in rheumatoid arthritis
    McGeer, PL
    Sibley, J
    [J]. NEUROBIOLOGY OF AGING, 2005, 26 (08) : 1199 - 1203
  • [20] A SIMPLE SALTING OUT PROCEDURE FOR EXTRACTING DNA FROM HUMAN NUCLEATED CELLS
    MILLER, SA
    DYKES, DD
    POLESKY, HF
    [J]. NUCLEIC ACIDS RESEARCH, 1988, 16 (03) : 1215 - 1215