The expression of SARS-CoV 2 co-receptors and glia reaction in eyes of normal and COVID-19 diseased patients

ABSTRACT

Purpose: With this research project we wanted to approach the question of whether SARS-CoV 2 can infect the eye. In order to infect ocular tissues, virus-specific receptors;coreceptors or proteases must be present in the eye tissue. SARS-CoV 2 uses the human angiotensin converting enzyme 2 (ACE2) receptor to enter cells. In addition, the mammalian serine protease TMPRSS2, the protease furin and the glycoprotein neuropilin are identified as relevant proteases for the interaction of the virus with ACE2. Last year, we were able to show that ACE2 is significantly more expressed in ocular tissue of covid patients. Here the expression level of the co-receptor and glia markers, as well as the present of virus was confirmed in this study. Methods: Seven eyes from donors without covid disease (COVID-) as well as ten fixed eyes from COVID-19 patients (COVID+) were analysed for their expression profile of ACE2, TMPRSS2, neuropilin and furin in the retina and cornea. The ocular tissues were examined for protein expression by immunohistochemical staining or for RNA expression by quantitative real-time PCR. In addition, viral spike protein was detected histologically in eyes, and expression profiles of GFAP and Iba-1 were assessed. Results: Similar to ACE2 and TMPRSS2, the two proteases neuropilin and furin were detected in the retina and cornea. Interestingly, the expression profile differed in terms of strength and localization, especially in the retina. The presence of the virus in both cornea and retina was also demonstrated by the detection of viral spike protein. In all COVID+ retinas, strong GFAP staining was observed as well as some Iba-1 positive cells, suggesting activation of macro- and microglia. Conclusions: Expression of ACE2, TMPRSS2, furin and neuropilin was demonstrated in COVID+ ocular tissues. In addition to the virus detection in retina and cornea, a glial reaction could also be observed. One can therefore assume an infection of the eye in these cases. However, in summary it can be said that an infection of the eye tissue is possible since all demanded receptors are present.