April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Docosahexaenoic Acid Protects From Early Retinal Degeneration and Attenuates Microglial Activation
T. Langmann; S. Ebert; K. Weigelt; Y. Walczak; W. Drobnik; R. Mauerer; D. A. H. Hume; B. H. F. Weber
Author Affiliations & Notes
  • T. Langmann
    Institute of Human Genetics, University of Regensburg, Regensburg, Germany
  • S. Ebert
    Institute of Human Genetics, University of Regensburg, Regensburg, Germany
  • K. Weigelt
    Institute of Human Genetics, University of Regensburg, Regensburg, Germany
  • Y. Walczak
    Institute of Human Genetics, University of Regensburg, Regensburg, Germany
  • W. Drobnik
    Synlab Medical Care Center, Weiden, Germany
  • R. Mauerer
    Synlab Medical Care Center, Weiden, Germany
  • D. A. H. Hume
    Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom
  • B. H. F. Weber
    Institute of Human Genetics, University of Regensburg, Regensburg, Germany
  • Footnotes
    Commercial Relationships  T. Langmann, None; S. Ebert, None; K. Weigelt, None; Y. Walczak, None; W. Drobnik, None; R. Mauerer, None; D.A.H. Hume, None; B.H.F. Weber, None.
  • Footnotes
    Support  German Research Foundation FOR1075 Project 4, Pro Retina Foundation
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 6253. doi:
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      T. Langmann, S. Ebert, K. Weigelt, Y. Walczak, W. Drobnik, R. Mauerer, D. A. H. Hume, B. H. F. Weber; Docosahexaenoic Acid Protects From Early Retinal Degeneration and Attenuates Microglial Activation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6253.

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Abstract

Purpose: : Microgliosis is a common phenomenon in retinal dystrophies. Our first goal was to perform a molecular and functional characterization of activated microglia in the retinoschisin-deficient (Rs1h-/Y) mouse model of inherited retinal degeneration. Moreover, we aimed to study the effects of of dietary docosahexaenoic acid (DHA) on retinal degeneration and microglia activity in Rs1h-/Y mice.

Methods: : To visualize and isolate activated microglia, Rs1h-/Y animals were crossed with transgenic MacGreen mice, which express the enhanced green fluorescent protein (EGFP) under the control of the macrophage-specific csf1r promoter. Microarray analysis and high-throughput real-time RT-PCR were performed for molecular profiling of cultured activated and resting microglia. A DHA supplementation study was carried out with Rs1h-/Y mice and lipid profiles of the retina, brain and plasma were determined by gas-chromatography mass-spectrometry. Retinal histology, photoreceptor apoptosis, inflammatory markers and microglia phenotypes were analyzed.

Results: : Lipid droplet-containing activated microglia were detected in retinal sections of early postnatal Rs1h-/Y / MacGreen mice before the onset of overt neuronal cell death. Microarray analysis of ex vivo isolated microglia revealed induction of a gene set involved in lipid droplet formation and eicosanoid synthesis. Analysis of the retinal phospholipid composition of Rs1h-/Y and wild-type retinas revealed a significant decrease in the omega-3-polyunsaturated fatty acid DHA. To establish a potential link between microglia activation, reduced DHA levels, and neurodegeneration in the retina, a dietary intervention study was performed. Female Rs1h-/- mice and their Rs1h-/Y litter were either subjected to a diet enriched with 2% DHA, or a standard chow. Supplementation with DHA enhanced photoreceptor survival and converted lipid-bloated microglia to a quiescent phenotype with reduced pro-inflammatory gene expression. As a consequence, retinal DHA levels may control the activity of microglia and thereby may affect the progression and extent of retinal degeneration.

Conclusions: : We conclude that dietary DHA supplementation could be a treatment option for inherited retinal degeneration that restores both microglial homeostasis and neuronal viability.

Keywords: microglia • lipids • retinal degenerations: cell biology 
© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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