June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Subretinal CD14+ monocytes, observed in geographic atrophy, induce loss of photoreceptor outer segments and lead to rod apoptosis.
Author Affiliations & Notes
  • Chiara M Eandi
    Eye Clinic, University Torino, Torino, Italy
    Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France
  • Elisa Dominguez
    Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France
  • Sophie Lavalette
    Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France
  • Shulong Hu
    Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France
  • Michael Housset
    Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France
  • Cheryl Mae Craft
    Mary D. Allen Lab for Vision Research, CSA 215, Los Angeles, CA
  • Michel Pâques
    Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France
  • José Sahel
    Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France
  • Xavier P Guillonneau
    Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France
    Université Pierre et Marie Curie, Paris, France
  • Florian Sennlaub
    Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France
    Université Pierre et Marie Curie, Paris, France
  • Footnotes
    Commercial Relationships Chiara Eandi, None; Elisa Dominguez, None; Sophie Lavalette, None; Shulong Hu, None; Michael Housset, None; Cheryl Craft, None; Michel Pâques, None; José Sahel, None; Xavier Guillonneau, None; Florian Sennlaub, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2372. doi:
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      Chiara M Eandi, Elisa Dominguez, Sophie Lavalette, Shulong Hu, Michael Housset, Cheryl Mae Craft, Michel Pâques, José Sahel, Xavier P Guillonneau, Florian Sennlaub; Subretinal CD14+ monocytes, observed in geographic atrophy, induce loss of photoreceptor outer segments and lead to rod apoptosis.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2372.

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

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Abstract 
 
Purpose
 

Rod photoreceptor cell loss has been shown to be particularly prominent in geographic atrophy (GA), and residual cones and rods within the geographic lesion lack their outer segment. GA is also associated with CCR2+subretinal inflammatory monocyte accumulation in and around the GA lesion and inflammatory monocytes have been shown to induce RPE cell death in vitro.<br /> It is not clear if or how the chronic subretinal monocyte accumulation participates in the pathological changes of photoreceptors in GA. We here evaluate the subretinal monocyte accumulation and photoreceptor phenotype in GA patients and investigated the influence of CD14+monocytes on photoreceptors ex vivo.<br />

 
Methods
 

CD14, rhodopsin, cone arrestin, L/M opsin and S opsin were visualized using immunohistochemistry on donor eyes from control subjects and GA patients. CD14+cells, cones and rods were quantified within the GA lesion and at increasing distances from the lesion. Adherent CD14+ human blood-derived monocytes were co-cultured with an overlying mouse retinal explant and photoreceptor apoptosis (TUNEL) and cone morphology (peanut agglutinine (PNA) immunohistochemistry) was analyzed after 18h.<br />

 
Results
 

Our results show the association of subretinal CD14+ monocytes accumulation with a 90% of the rod population in donor eyes with GA lesions. Residual cones within the lesion were 50% of the extrafoveal normal cone count. However residual cones and rods within the lesion were not distributed equally and lacked their outer segments. In retinal explants co-cultured with CD14+monocytes, apoptosis of rod photoreceptors dramatically increased (1600%), but the number of PNA+ cone photoreceptors was not affected. Cones and rods invariably had lost their outer segments compared to controls.

 
Conclusions
 

Our experiments confirm the subretinal accumulation of monocytes and photoreceptor changes in GA lesions. Our results suggest that subretinal inflammatory monocytes contribute to rod cell loss and might participate in the loss of cone and rod outer segments observed in the residual photoreceptors within the lesion. Inhibition of subretinal monocyte accumulation in GA might help inhibit rod apoptosis.

 
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