June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Analysis of plasma HtrA1 concentrations in age-related macular degeneration
Author Affiliations & Notes
  • Sofie Clasina Anna ten Brink
    Radboudumc Afdeling Oogheelkunde, Nijmegen, Gelderland, Netherlands
  • Bjorn Bakker
    Radboudumc Afdeling Oogheelkunde, Nijmegen, Gelderland, Netherlands
  • Carel C B Hoyng
    Radboudumc Afdeling Oogheelkunde, Nijmegen, Gelderland, Netherlands
  • Yara T E Lechanteur
    Radboudumc Afdeling Oogheelkunde, Nijmegen, Gelderland, Netherlands
  • Caroline C W Klaver
    Ophthalmology/Epidemiology, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
    Radboudumc Afdeling Oogheelkunde, Nijmegen, Gelderland, Netherlands
  • Anneke I Den Hollander
    Radboudumc Afdeling Oogheelkunde, Nijmegen, Gelderland, Netherlands
  • Footnotes
    Commercial Relationships   Sofie ten Brink Boehringer Ingelheim Pharma GmbH & Co. KG, Code F (Financial Support); Bjorn Bakker None; Carel Hoyng None; Yara Lechanteur None; Caroline Klaver Thea Pharma, Code C (Consultant/Contractor), Bayer, Code F (Financial Support); Anneke Den Hollander AbbVie Inc., Code E (Employment)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 477 – A0014. doi:
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      Sofie Clasina Anna ten Brink, Bjorn Bakker, Carel C B Hoyng, Yara T E Lechanteur, Caroline C W Klaver, Anneke I Den Hollander; Analysis of plasma HtrA1 concentrations in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2022;63(7):477 – A0014.

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

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Abstract

Purpose : The responsible gene for the association at the Age-Related Maculopathy Susceptibility 2-High-temperature requirement protein A1 (ARMS2-HTRA1) locus with age-related macular degeneration (AMD) is still a matter of debate. A previous study demonstrated increased systemic HtrA1 protein concentrations in AMD, which were suggested to lead to subsequent degradation of Bruch’s membrane and eventual choroidal neovascularization in AMD (Pan et al 2021, J Biol Chem 296:100456). We aimed to verify these results and therefore performed an enzyme-linked immunoassay (ELISA) targeting this protein in plasma samples of a case-control study.

Methods : A total of 200 advanced AMD patients and 200 controls without AMD were selected from the European Genetic Database (EUGENDA). An ELISA was performed for plasma HtrA1 concentrations. Multiple linear regression analysis with backward elimination based on adjusted-R2 was used to assess the association between the HtrA1 plasma concentrations and AMD.

Results : We excluded 9 AMD and 3 control samples due to an absorption below the standard curve. Median plasma level of Htra1 was slightly higher in AMD patients (514 pg/ml) than in controls (500 pg/ml). However, the association between HtrA1 plasma level and AMD adjusted for age and age x AMD status was not significant (R2 = 0.011; p = 0.10).

Conclusions : This study was unable to replicate the association between HtrA1 plasma concentrations and AMD. Further study is required to elucidate the causal gene dysfunction at the ARMS2-HTRA1 locus in AMD.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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