July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Microglia exhibit distinct mitochondrial signatures in retinal degeneration
Author Affiliations & Notes
  • Margaret Maes
    Institute of Science and Technology Austria, Klosterneuburg, Austria
  • Sandra Siegert
    Institute of Science and Technology Austria, Klosterneuburg, Austria
  • Footnotes
    Commercial Relationships   Margaret Maes, None; Sandra Siegert, None
  • Footnotes
    Support  Institute of Science and Technology Postdoctoral Fellowship
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3999. doi:
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      Margaret Maes, Sandra Siegert; Microglia exhibit distinct mitochondrial signatures in retinal degeneration . Invest. Ophthalmol. Vis. Sci. 2019;60(9):3999.

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

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Abstract

Purpose : Microglia have emerged as a critical neuroinflammatory component in several retinal degenerative diseases, yet our knowledge of how they transition to a reactive state is limited. Here, we will test whether mitochondria alterations within microglia indicate their proinflammatory transition in retinal degenerative models.

Methods : To observe reactive microglia in the outer plexiform layer (OPL) or ganglion cell layer (GCL), the rd10 mouse or optic nerve crush (ONC) models were used, respectively. For the rd10 model (RD), P25 animals and corresponding wildtype (WT) controls received subretinal injections of AAV2/6-CD68-mito-Dendra2 (n=6 mice/genotype). For ONC, adult mice expressing a microglia-specific mitochondrial tag (Cx3Cr1-CreERT2 x Pham) were subject to ONC surgery and compared to naïve (n=6 mice) and contralateral control (OD) (n=5 mice). Metrics from volume rendering analysis were assessed on a per cell basis and included mitochondria volume, mitochondrial localization, microglia sholl analysis, and CD68 percentage of microglia volume. Statistics were calculated using a two-tailed student’s t-test.

Results : Photoreceptor degeneration in the rd10 model increased the percentage of CD68 in OPL microglia (RD vs Naïve: P=0.04) as well as the number of sholl intersections closer to the soma in RD vs WT or Naïve conditions. Microglia in the OPL showed a reduction in mitochondria volume (RD vs Naïve: P=0.03) and distance from the soma, which were not observed in the inner plexiform layer (IPL) (volume RD vs Naïve: P=0.13). ONC-induced retinal ganglion cell degeneration resulted in reactive microglia in the IPL indicated by an increase of CD68 volume in microglia (OS vs. OD: P=0.01, OS vs Naïve: P=0.01), and increased sholl intersections closer to the soma in OS vs OD or Naïve conditions. The average mitochondrial volume was reduced in the GCL and IPL (OS vs Naïve: P=0.05, P=0.02, respectively), but not in the OPL (OS vs Naïve: P=0.08). Mitochondria distance from the soma was also reduced in GCL and IPL microglia.

Conclusions : In both rd10 and ONC models of retinal degeneration, microglia transition to a reactive state, which is dependent on the retinal layer where degeneration occurs. Reactive microglia exhibit reduced mitochondria volume and increased perinuclear localization in comparison to corresponding controls.

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

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