Microglia activation and neuronal alterations in retinas from COVID-19 patients: correlation with clinical parameters

BackgroundDifferent ocular alterations have been described in patients with coronavirus disease 2019 (COVID-19). Our aim was to determine whether COVID-19 affected retinal cells and establish correlations with clinical parameters.MethodsRetinal sections and flat-mount retinas from human donors with COVID-19 (n = 16) and controls (n = 15) were immunostained. The location of angiotensin-converting enzyme 2 (ACE2) and the morphology of microglial cells, Muller cells, astrocytes, and photoreceptors were analyzed by confocal microscopy. Microglial quantification and the area occupied by them were measured. Correlations among retinal and clinical parameters were calculated.ResultsACE2 was mainly located in the Muller cells, outer segment of cones and retinal pigment epithelium. Cell bodies of Muller cells in COVID-19 group showed greater staining of ACE2 and cellular retinaldehyde-binding protein (CRALBP). The 81.3% of COVID-19 patients presented disorganization of honeycomb-like pattern formed by Muller cells. Gliosis was detected in 56.3% of COVID-19 patients compared to controls (40%) as well as epiretinal membranes (ERMs) or astrocytes protruding (50%). Activated or ameboid-shape microglia was the main sign in the COVID-19 group (93.8%). Microglial migration towards the vessels was greater in the COVID-19 retinas (P < 0.05) and the area occupied by microglia was also reduced (P < 0.01) compared to control group. Cone degeneration was more severe in the COVID-19 group. Duration of the disease, age and respiratory failure were the most relevant clinical data in relation with retinal degeneration.ConclusionsThe retinas of patients with COVID-19 exhibit glial activation and neuronal alterations, mostly related to the inflammation, hypoxic conditions, and age.

Automated summary

This study aimed to determine whether COVID-19 affected retinal cells and establish correlations with clinical parameters. Immunostaining and confocal microscopy analysis revealed that Muller cells in COVID-19 patients showed stronger expression of ACE2 and CRALBP, and the retinas exhibited glial activation and neuronal alterations, mainly related to inflammation, hypoxic conditions, and age.