ABSTRACT
BACKGROUND: Different 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. METHODS: Retinal 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, Müller 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. RESULTS: ACE2 was mainly located in the Müller cells, outer segment of cones and retinal pigment epithelium. Cell bodies of Müller 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 Müller 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. CONCLUSIONS: The retinas of patients with COVID-19 exhibit glial activation and neuronal alterations, mostly related to the inflammation, hypoxic conditions, and age.
ABSTRACT
Purpose: Ocular and eye fundus alterations have been described in COVID‐19 patients. In this study, the aim was to establish several stages of response to damage in the retinal cells from human donors with COVID‐19 and analyse their relationship with clinical parameters. Methods: Retinal sections and flat‐mount retinas from human donors with COVID‐19 (n = 16) and control (n = 12) were analysed with immunohistochemistry. The location of angiotensin‐converting enzyme 2 (ACE2) and the morphology of microglial cells, Müller cells, astrocytes, and photoreceptors were evaluated by confocal microscopy. Microglial analysis and cell death were measured. Clinical data were correlated with different retinal parameters. Results: Müller cells, outer segment of cones and retinal pigment epithelium presented the ACE2 protein. Larger staining of ACE2 and cellular retinaldehyde–binding protein (CRALBP) was found in the cell bodies of Müller cells in COVID‐19 group. Disorganization of honeycomb‐like pattern formed by Müller cells and disruption of external limiting membrane were observed in the 81.3% of COVID‐19 patients. The 53.3% of COVID‐19 patients showed reactive gliosis as well as astrocytes protruding and epiretinal membranes. Cone degeneration was aggravated in the COVID‐19 group. Activated or ameboid‐shape microglia was found in the 93.8% of COVID‐19 patients. Most retinas showed a reduction of the area occupied by microglia and presented microglial nodules around vessels. Retinal degeneration in COVID‐19 group correlated with the duration of the disease (ro: 0.655;p < 0.01) and age (ro: −0.5;p < 0.05). Moreover, microglia activation was correlated with blood oxygen levels (ro: −0.554;p < 0.05). Conclusions: Different stages of glial activation and neuronal alterations are present in COVID‐19 retinas and are significantly correlated with the duration of the disease, age and respiratory failure.