Subretinal mononuclear phagocytes induce cone segment loss via IL-1β
Abstract
Photo-transduction in cone segments (CS) is crucial for high acuity daytime vision. For ill-defined reasons, CS degenerate in retinitis pigmentosa (RP) and in the transitional zone (TZ) of atrophic zones (AZ), which characterize geographic atrophy (GA). Our experiments confirm the loss of cone segments (CS) in the TZ of GA patients and show their association with subretinal CD14+mononuclear phagocyte (MP) infiltration that is also reported in RP. Using human and mouse MPs in vitro and inflammation-prone Cx3cr1GFP/GFP mice in vivo, we demonstrate that MP derived IL-1β leads to severe CS degeneration. Our results strongly suggest that subretinal MP accumulation participates in the observed pathological photoreceptor changes in these diseases. Inhibiting subretinal MP accumulation or Il-1β might protect the CS and help preserve high acuity daytime vision in conditions characterized by subretinal inflammation, such as AMD and RP.
Article and author information
Author details
Funding
Agence Nationale de la Recherche (MACLEAR)
- Sébastien Augustin
- Elisa Dominguez
- Sophie Lavalette
- Shulong Justin Hu
- Lourdes Siquieros
- José-Alain Sahel
- Michel Paques
- Xavier Guillonneau
- Florian Sennlaub
Labex (lifescience)
- Chiara M Eandi
- Hugo Charles Messance
- Sébastien Augustin
- Elisa Dominguez
- Sophie Lavalette
- Shulong Justin Hu
- Lourdes Siquieros
- José-Alain Sahel
- Ramin Tadayoni
- Michel Paques
- Xavier Guillonneau
- Florian Sennlaub
adps-allianz
- Chiara M Eandi
- Hugo Charles Messance
- Sébastien Augustin
- Elisa Dominguez
- Sophie Lavalette
- Shulong Justin Hu
- Lourdes Siquieros
- José-Alain Sahel
- Ramin Tadayoni
- Michel Paques
- Xavier Guillonneau
- Florian Sennlaub
National Institutes of Health (EY015851)
- Cheryl Mae Craft
National Institutes of Health (EY03040)
- Cheryl Mae Craft
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental protocols and procedures were approved by the local animal care ethics committee (00156.02; C 92-032-02 )
Human subjects: Volunteers provided written and informed consent for the human monocyte expression studies, which were approved by the Centre national d'ophthalmologie des Quinze-Vingt hospital (Paris, France) ethics committees (no. 913572)
Copyright
© 2016, Eandi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,579
- views
-
- 331
- downloads
-
- 73
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Detecting causal relations structures our perception of events in the world. Here, we determined for visual interactions whether generalized (i.e. feature-invariant) or specialized (i.e. feature-selective) visual routines underlie the perception of causality. To this end, we applied a visual adaptation protocol to assess the adaptability of specific features in classical launching events of simple geometric shapes. We asked observers to report whether they observed a launch or a pass in ambiguous test events (i.e. the overlap between two discs varied from trial to trial). After prolonged exposure to causal launch events (the adaptor) defined by a particular set of features (i.e. a particular motion direction, motion speed, or feature conjunction), observers were less likely to see causal launches in subsequent ambiguous test events than before adaptation. Crucially, adaptation was contingent on the causal impression in launches as demonstrated by a lack of adaptation in non-causal control events. We assessed whether this negative aftereffect transfers to test events with a new set of feature values that were not presented during adaptation. Processing in specialized (as opposed to generalized) visual routines predicts that the transfer of visual adaptation depends on the feature similarity of the adaptor and the test event. We show that the negative aftereffects do not transfer to unadapted launch directions but do transfer to launch events of different speeds. Finally, we used colored discs to assign distinct feature-based identities to the launching and the launched stimulus. We found that the adaptation transferred across colors if the test event had the same motion direction as the adaptor. In summary, visual adaptation allowed us to carve out a visual feature space underlying the perception of causality and revealed specialized visual routines that are tuned to a launch’s motion direction.
-
- Neuroscience
Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.