June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
The extracellular vesicle marker, Alix, co-localizes with Fibulin-3 puncta located in human drusen deposits
Author Affiliations & Notes
  • Stephanie Louise Grillo
    Ophthalmology, Penn State University, Hershey, Pennsylvania, United States
  • Justin Etzel
    Ophthalmology, Penn State University, Hershey, Pennsylvania, United States
  • Sarah Weber
    Ophthalmology, Penn State University, Hershey, Pennsylvania, United States
  • Cassandra Ondeck
    Ophthalmology, Penn State University, Hershey, Pennsylvania, United States
  • Weiwei Wang
    Ophthalmology, Penn State University, Hershey, Pennsylvania, United States
  • Yuanjun Zhao
    Ophthalmology, Penn State University, Hershey, Pennsylvania, United States
  • Alistair J Barber
    Ophthalmology, Penn State University, Hershey, Pennsylvania, United States
  • Jeffrey Sundstrom
    Ophthalmology, Penn State University, Hershey, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Stephanie Grillo, None; Justin Etzel, None; Sarah Weber, None; Cassandra Ondeck, None; Weiwei Wang, None; Yuanjun Zhao, None; Alistair Barber, None; Jeffrey Sundstrom, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2265. doi:
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      Stephanie Louise Grillo, Justin Etzel, Sarah Weber, Cassandra Ondeck, Weiwei Wang, Yuanjun Zhao, Alistair J Barber, Jeffrey Sundstrom; The extracellular vesicle marker, Alix, co-localizes with Fibulin-3 puncta located in human drusen deposits. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2265.

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

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Abstract

Purpose : Purpose: Fibulin-3 (Fib3) is a secreted glycoprotein that is expressed in the retina and has been associated with drusen formation in age-related macular degeneration (AMD). The purpose of this study was to assess whether Fib3 is associated with extracellular vesicles (EVs) in drusen from non-diseased and AMD human donors.

Methods : Methods: De-identified sections of human eyes were received from the National Disease Research Institute (NDRI, Philadelphia). Donor eyes were either non-diseased (no known ocular pathology) or had been diagnosed with AMD. Retinal cryostat sections were labeled with primary antibodies targeted to Fib3, Apolipoprotein E (ApoE; a drusen marker), and ALG-2 interacting protein X (Alix, an EV marker) for confocal imaging (Leica TCS SP8).

Results : Results: Fib3 puncta was detected on the apical region of the RPE layer and within large AMD drusen. Alix-positive puncta was also detected in AMD drusen, where a number were Fib3-positive and the remaining were Fib3-negative. Similarly, there were Fib3-positive puncta that were Alix-negative. Fib3 and Alix also showed a degree of colocalization in the photoreceptor outer segments of the neural retina.

Conclusions : Conclusions: Our data suggests that the Alix-positive puncta are EV-rich populations which are accumulated, together with Fib3, within the drusen matrix during AMD. The EV populations possess a heterogeneous cargo content i.e. some carry the Fib3 protein and some do not. This shows a potential pathological role for Fib3 in AMD drusen formation which may utilize RPE-derived EVs for delivery.

This is a 2020 ARVO Annual Meeting abstract.

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