July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
The presence of ADAMs in the eye: Exploring a promising therapeutic target for age-related macular degeneration
Author Affiliations & Notes
  • Mackenzie Ann Campbell
    Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • Gurkaran Singh Sarohia
    Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • Matthew Campbell
    Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  • Jing Z Cui
    Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  • Joanne A Matsubara
    Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  • Footnotes
    Commercial Relationships   Mackenzie Campbell, None; Gurkaran Sarohia, None; Matthew Campbell, None; Jing Cui, None; Joanne Matsubara, None
  • Footnotes
    Support  CIHR MOP-126195
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1239. doi:https://doi.org/
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      Mackenzie Ann Campbell, Gurkaran Singh Sarohia, Matthew Campbell, Jing Z Cui, Joanne A Matsubara; The presence of ADAMs in the eye: Exploring a promising therapeutic target for age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1239. doi: https://doi.org/.

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

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Abstract

Purpose : Age-related macular degeneration (AMD) is a progressive neurodegenerative disease and the primary cause of irreversible vision loss in the elderly. Innate immunity plays a critical role in the development, progression, and treatment of AMD. This study focuses on “a disintegrin and metalloproteases, ADAMs”, a group of active proteases that may contribute to chronic proinflammation in the development of AMD.

Methods : Five groups of human donor eyes were obtained: AMD eyes with drusen (n=4) or with geographic atrophy (GA) (n=5), non-AMD eyes with soft drusen (n=10) or with numerous large drusen (n=12), and age-matched control eyes (n=4). The eye tissues were processed for standard immunohistochemistry using ADAM10 or ADAM17 mouse monoclonal antibodies, developed with chromogenic label (AEC), and imaged with brightfield microscopy.

Results : The RPE and choroid of AMD eyes with drusen stained for ADAM10 in 100% and 75% of samples, respectively. The RPE and choroid of AMD eyes with GA stained for ADAM10 in 80% and 75% of samples, respectively. The RPE and choroid of non-AMD eyes with soft drusen stained for ADAM10 in 50% and 60% of samples, respectively. The RPE and choroid of non-AMD eyes with numerous large drusen stained for ADAM10 in 50% and 50% of samples, respectively. The RPE and choroid of age-matched control eyes stained for ADAM10 in 0% and 50% of samples, respectively. The RPE and choroid of AMD eyes with drusen stained for ADAM17 in 25% and 75% of samples, respectively. The RPE and choroid of AMD eyes with GA stained for ADAM17 in 25% and 100% of samples, respectively. The RPE and choroid of non-AMD eyes with soft drusen stained for ADAM17 in 20% and 50% of samples, respectively. The RPE and choroid of non-AMD eyes with numerous large drusen stained for ADAM17 in 42% and 67% of samples, respectively. The RPE and choroid of age-matched control eyes stained for ADAM17 in 50% and 25% of samples, respectively.

Conclusions : There are higher levels of ADAM10 in both RPE and choroid of AMD eyes compared to non-AMD and age-matched control eyes. There are higher levels of ADAM17 in the choroid only of AMD eyes compared to non-AMD and age-matched control eyes. These findings suggest that ADAM10 and ADAM17 are present in outer retina, and that their distribution may be related to early and late stage AMD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

The expression of ADAM10 and ADAM17 in AMD, non-AMD, and age-matched control eyes.

The expression of ADAM10 and ADAM17 in AMD, non-AMD, and age-matched control eyes.

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