June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Transcriptome Analysis of Amyloid-β in the Rat Retina Reveals Important Link to Pathological Processes Implicated in Age-related Macular Degeneration
Author Affiliations & Notes
  • Amanda Qarawani
    Technion Israel Institute of Technology, Haifa, Haifa, Israel
  • Efrat Naaman
    Rambam Health Care Campus Department of Ophthalmology, Haifa, Haifa, Israel
  • rony Ben-Zvi Elimelech
    Technion Israel Institute of Technology, Haifa, Haifa, Israel
  • Shadi Safuri
    Rambam Health Care Campus Department of Ophthalmology, Haifa, Haifa, Israel
  • Shiri Zayit-Soudry
    Technion Israel Institute of Technology, Haifa, Haifa, Israel
    Rambam Health Care Campus Department of Ophthalmology, Haifa, Haifa, Israel
  • Footnotes
    Commercial Relationships   Amanda Qarawani None; Efrat Naaman None; rony Ben-Zvi Elimelech None; Shadi Safuri None; Shiri Zayit-Soudry None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2734. doi:
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      Amanda Qarawani, Efrat Naaman, rony Ben-Zvi Elimelech, Shadi Safuri, Shiri Zayit-Soudry; Transcriptome Analysis of Amyloid-β in the Rat Retina Reveals Important Link to Pathological Processes Implicated in Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2734.

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

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Abstract

Purpose : The complex pathophysiology of age-related macular degeneration (AMD) is poorly understood. Recent clinical data highlighted disruption of the complement system, lipid metabolism, and oxidative stress responses as essential pathways in AMD, yet little is known about the triggers that give rise to these events. Previous studies have shown that Amyloid-β (Aβ) is a significant component of drusen, potentially involved in the pathophysiology of AMD. We have previously found that Aβ species possess differential retinal toxicity in rats. Here, we aimed to further investigate the pathogenic cascades which are triggered in the retina by Aβ fibrils.

Methods : Wild-type Sprague Dawley rats were injected intravitreally with 10µl of fibrillar Aβ42 (n=3) or vehicle only in their right eye (n=3). The rats were sacrificed at 4 days and 30 days post injection and their eyes were enucleated. In each eye, a circular incision was made around the limbus and the neurosensory retina was delicately explanted. High-quality RNA samples were used for retinal transcriptome analysis and treated retinas were compared with controls. Gene ontology enrichment analysis and ingenuity pathway analysis were used to identify core pathways.

Results : At 4 days following treatment with Aβ fibrils, 13 genes were differentially expressed in experimental versus control retinas. Significantly dysregulated genes including APOE, ABCA1, CAV1, CAV2, PLTP were identified as key markers. Genes implicated in positive regulation of cholesterol efflux were significantly increased, while genes implicated in cholesterol synthesis were decreased. Pathway analysis indicated dysregulation in cholesterol efflux, cholesterol metabolic process, and lipid localization. At 30 days following treatment with Aβ fibrils, 27 genes were differentially expressed in experimental versus control retinas. The Expression of genes implicated in negative regulation of innate immune response was significantly increased.

Conclusions : Our results provide insight into the retinal pathogenicity of Aβ42 and highlight its involvement in retinal cholesterol metabolism and innate response. These cascades overlap with clinical data from AMD patients; which highlights the pathophysiological significance of Aβ in drusen and supports its role as an initiator of pathological cascades in the retina.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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