June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Retinas of human donors with COVID-19 disease show morphological alterations and signs of inflammation including glial activation
Author Affiliations & Notes
  • Henar Albertos-Arranz
    Physiology, Genetics and Microbiology, Universitat d'Alacant Facultad de Ciencies, Alacant, Comunitat Valenciana, Spain
  • Natalia Martínez-Gil
    Physiology, Genetics and Microbiology, Universitat d'Alacant Facultad de Ciencies, Alacant, Comunitat Valenciana, Spain
  • Xavier Sánchez-Sáez
    Physiology, Genetics and Microbiology, Universitat d'Alacant Facultad de Ciencies, Alacant, Comunitat Valenciana, Spain
  • Agustina Noailles
    Physiology, Genetics and Microbiology, Universitat d'Alacant Facultad de Ciencies, Alacant, Comunitat Valenciana, Spain
  • María José Ruiz-Pastor
    Physiology, Genetics and Microbiology, Universitat d'Alacant Facultad de Ciencies, Alacant, Comunitat Valenciana, Spain
  • Carla Sánchez-Castillo
    Physiology, Genetics and Microbiology, Universitat d'Alacant Facultad de Ciencies, Alacant, Comunitat Valenciana, Spain
  • Clara Monferrer-Adsuara
    Ophthalmology, General University Hospital Consortium of Valencia, Valencia, Comunidad Valenciana, Spain
  • Lidia Remolí-Sargues
    Ophthalmology, General University Hospital Consortium of Valencia, Valencia, Comunidad Valenciana, Spain
  • Pedro Lax
    Physiology, Genetics and Microbiology, Universitat d'Alacant Facultad de Ciencies, Alacant, Comunitat Valenciana, Spain
  • Ramón Calvo-Andrés
    Ophthalmology, General University Hospital Consortium of Valencia, Valencia, Comunidad Valenciana, Spain
  • Nicolas Cuenca
    Physiology, Genetics and Microbiology, Universitat d'Alacant Facultad de Ciencies, Alacant, Comunitat Valenciana, Spain
  • Footnotes
    Commercial Relationships   Henar Albertos-Arranz None; Natalia Martínez-Gil None; Xavier Sánchez-Sáez None; Agustina Noailles None; María José Ruiz-Pastor None; Carla Sánchez-Castillo None; Clara Monferrer-Adsuara None; Lidia Remolí-Sargues None; Pedro Lax None; Ramón Calvo-Andrés None; Nicolas Cuenca None
  • Footnotes
    Support  Spanish Ministry of Science and Innovation (FEDER-PID2019-106230RB-I00), Spanish Ministry of Universities (FPU16/04114 and FPU18/02964), National Institute of Health Carlos III (RETICS-FEDER RD16/0008/0016), and Generalitat Valenciana (IDIFEDER/2017/064, PROMETEO/2021/024).
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 975 – F0372. doi:
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      Henar Albertos-Arranz, Natalia Martínez-Gil, Xavier Sánchez-Sáez, Agustina Noailles, María José Ruiz-Pastor, Carla Sánchez-Castillo, Clara Monferrer-Adsuara, Lidia Remolí-Sargues, Pedro Lax, Ramón Calvo-Andrés, Nicolas Cuenca; Retinas of human donors with COVID-19 disease show morphological alterations and signs of inflammation including glial activation. Invest. Ophthalmol. Vis. Sci. 2022;63(7):975 – F0372.

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

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Abstract

Purpose : Different signs of inflammation have been described in the brains of COVID-19 patients. In the retina, the fundus eye exam of these patients shows cotton wool spots, microhemorrhages, and a decrease in vascular density. However, morphological alterations of retinal cells in these patients are unknown. Thus, the aim was to analyze the morphological changes of the retinal cells from human donors with COVID-19 to establish several stages of response to damage in these cells and to define correlations with clinical parameters.

Methods : The retinas of human donors with COVID-19 (n = 16) and control subjects (n = 12) obtained from the General University Hospital Consortium of Valencia were analyzed. Immunohistochemical stainings were performed on transversal sections or flat-mount retinas to study photoreceptors, microglial cells, Müller cells, astrocytes, and the presence of ACE2. TUNEL assays and confocal microscopy imaging were carried out. Correlations were calculated between retinal and clinical parameters.

Results : Mean age of COVID-19 and control group were 80±10 and 70±8 years respectively. Müller cells, outer segment of cones and retinal pigment epithelium presented ACE2 staining. Larger staining of ACE2 and CRALBP was observed in cell bodies of Müller cells in COVID group. Disorganization of honeycomb-like pattern formed by Müller cells in the outer nuclear layer and disruption of external limiting membrane was found in the 81.3% of COVID patients. The 56.3% of COVID patients showed gliosis compared to controls (40%). COVID-19 retinas also presented epiretinal membranes and astrocytes protruding to vitreous humor. The 93.8% of COVID-19 patients had activated or ameboid-shape microglia. Microglial nodules around vessels and a reduction of the area occupied by microglia in these retinas were observed. COVID-19 group showed a more severe degeneration of cones. Cone degeneration correlated with Müller cell activation. Age of COVID patients correlated inversely with total retinal degeneration.

Conclusions : Morphological alterations in the cone photoreceptors as well as glial activation showing an inflammatory state of the retina were observed in COVID-19 patients.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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