June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Complement and inflammation gene expression in an age-related macular degeneration (AMD) transmitochondrial cybrid model
Author Affiliations & Notes
  • Javier Cáceres-del-Carpio
    Gavin Herbert Eye Institute - UCI, Irvine, CA
  • Sonali R Nashine
    Gavin Herbert Eye Institute - UCI, Irvine, CA
  • Rodrigo Donato Costa
    Gavin Herbert Eye Institute - UCI, Irvine, CA
    Instituto Donato Oftalmologia, Poço de Caldas,, Brazil
  • Young Gyun Kim
    Gavin Herbert Eye Institute - UCI, Irvine, CA
  • Kunal Thaker
    Gavin Herbert Eye Institute - UCI, Irvine, CA
  • Tej Patel
    Gavin Herbert Eye Institute - UCI, Irvine, CA
  • Carolina Yañez
    Gavin Herbert Eye Institute - UCI, Irvine, CA
  • Baruch Kuppermann
    Gavin Herbert Eye Institute - UCI, Irvine, CA
  • Cristina M Kenney
    Gavin Herbert Eye Institute - UCI, Irvine, CA
    Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA
  • Footnotes
    Commercial Relationships Javier Cáceres-del-Carpio, None; Sonali Nashine, None; Rodrigo Costa, None; Young Gyun Kim, None; Kunal Thaker, None; Tej Patel, None; Carolina Yañez, None; Baruch Kuppermann, None; Cristina Kenney, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 826. doi:
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      Javier Cáceres-del-Carpio, Sonali R Nashine, Rodrigo Donato Costa, Young Gyun Kim, Kunal Thaker, Tej Patel, Carolina Yañez, Baruch Kuppermann, Cristina M Kenney; Complement and inflammation gene expression in an age-related macular degeneration (AMD) transmitochondrial cybrid model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):826.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Age-related macular degeneration (AMD) is the leading cause of vision loss in individuals over 50 years old. Previous studies have reported association between AMD, mitochondrial DNA (mtDNA) and key molecules of the complement and inflammation pathways. A transmitochondrial cybrid model has been established, where mitochondria-depleted ARPE-19 cells were fused with platelets of individuals with AMD and age-match normal controls. The purpose of this study is to evaluate the variations in expression of complement and inflammation related genes in AMD and normal cybrids.

Methods: To create cybrids, mitochondria-deficient (Rho0) human ARPE-19 cells were fused with platelets isolated from age-matched non-AMD individuals and AMD patients (n=4, for each group). All cybrids carried the same nuclear genes but varied in mtDNA content. RNA was extracted from cybrids, cDNA was synthesized and quantitative RT-PCR was performed to analyze changes in expression of complement factor H (CFH), decay accelerating factor for complement (CD55), complement regulatory protein (CD59), complement factor I (CFI), complement factor properdin (CFP), interleukin 1 beta (IL-1β), interleukin 33 (IL-33) and transforming growth factor alpha (TGFA).

Results: AMD cybrids showed increased gene expression of CFH (2.3-fold, P=0.03), CD59 (7.2-fold, P<0.0001), CFI (4.9-fold, p=0.0007), CFP (11.97-fold, p<0.0001), IL-1β (3.4-fold, p=0.02) and TGFA (4.1-fold, p=0.0005) compared to normal cybrids. However, a significant decrease in the expression of CD55 (0.47-fold, P<0.0001) and IL-33 (0.3-fold, p=0.005) was observed in AMD cybrids compared to normal cybrids.

Conclusions: Since all cybrids had the same nuclear DNA content and differed only in mtDNA content, the observed changes in complement and inflammation gene expression can be attributed to mtDNA variations. Our findings suggest that AMD may be associated with mtDNA variants that affect the expression of critical complement and inflammation genes. Further studies are needed to clarify the relationship between the mitochondrial genome and AMD phenotype.

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