Subretinal mononuclear phagocytes induce cone segment loss via IL-1β

Chiara M Eandi; Hugo Charles Messance; Sébastien Augustin; Elisa Dominguez; Sophie Lavalette; Valérie Forster; Shulong Justin Hu; Lourdes Siquieros; Cheryl Mae Craft; José-Alain Sahel; Ramin Tadayoni; Michel Paques; Xavier Guillonneau; Florian Sennlaub

doi:10.7554/eLife.16490

Subretinal mononuclear phagocytes induce cone segment loss via IL-1β

Elife. 2016 Jul 20:5:e16490. doi: 10.7554/eLife.16490.

Authors

Chiara M Eandi^{1

2

3

4}, Hugo Charles Messance^{1

2}, Sébastien Augustin^{1

2}, Elisa Dominguez^{1

2}, Sophie Lavalette^{1

2}, Valérie Forster^{1

2}, Shulong Justin Hu^{1

2}, Lourdes Siquieros^{1

2}, Cheryl Mae Craft^{5

6

7

8}, José-Alain Sahel^{1

2

9}, Ramin Tadayoni^{1

2

10}, Michel Paques^{1

2

9}, Xavier Guillonneau^{1

2}, Florian Sennlaub^{1

2}

Affiliations

¹ Sorbonne Universités, UPMC University Paris 06, INSERM, CNRS, Paris, France.
² Institut de la Vision, Paris, France.
³ Department of Clinical Science, University of Torino, Torino, Italy.
⁴ Eye Clinic, University of Torino, Torino, Italy.
⁵ Mary D. Allen Laboratory for Vision Research, Keck School of Medicine of the University of Southern California, Los Angeles, United States.
⁶ University of Southern California Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, United States.
⁷ Department of Ophthalmology and Cell, Keck School of Medicine of the University of Southern California, Los Angeles, United States.
⁸ Department of Neurobiology, Keck School of Medicine of the University of Southern California, Los Angeles, United States.
⁹ Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DHOS CIC 503, Paris, France.
¹⁰ Department of Ophthalmology, Hôpital Lariboisièr, Paris, France.

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 patients with GA 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 Cx3cr1(GFP/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.

Keywords: age-related macular degeneration; human; human biology; interleukin; macrophages; medicine; mouse; neuroscience; outer segments; retinitis pigmentosa; subretinal space.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Geographic Atrophy / pathology*
Geographic Atrophy / physiopathology*
Humans
Interleukin-1beta / metabolism*
Mice
Phagocytes / immunology*
Retina / pathology*
Retinal Cone Photoreceptor Cells / physiology*

Substances

Interleukin-1beta

Abstract

Publication types

MeSH terms

Substances

Grants and funding