**Abstract**

The current COVID-19 pandemic has affected more than 100 million people and resulted in morbidity and mortality around the world. Even though the disease caused by SARS-CoV-2 is characterized by respiratory tract involvement, previous and recent data also indicates ocular manifestation. Not surprisingly, cell entry point of the virus, ACE2 receptor, is widely expressed in ocular tissues ranging from conjunctiva to retina. Despite the sensibility of ocular tissues, the sophisticated defense mechanism of the eye might eliminate viral transmission. Nevertheless, the potential of systemic transmission through the nasolacrimal duct may not be eliminated. In the case of ocular involvement, the disease outcomes might be as treatable as conjunctivitis or as serious as retinal degeneration and the treatment regimen vary accordingly. Within these contingencies, our aim with this chapter is to shed light on molecular bases of SARS-CoV-2 infection, systemic invasiveness following ocular transmission, manifestation and permanent effects on ocular tissues.

**Keywords:** COVID-19, SARS-CoV-2, conjunctivitis, conjunctiva, retina, ACE2, TMPRSS2

### **1. Introduction**

Coronaviruses are enveloped, positive-sense RNA viruses belonging to the subfamily Coronavirinae in the family Coronaviridae and cause serious respiratory ailments in humans [1]. In the last 20 years, three different types of coronavirus, including Middle-East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, respectively, have caused severe respiratory tract infections and fatal outbreaks. SARS-CoV-2 emerged in Wuhan, China in December 2019 and has rapidly become an international health emergency [2]. In March 2020, the World Health Organization (WHO) has declared novel coronavirus disease 2019 (COVID-19) pandemic.

SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor for viral entry, as in SARS-CoV [3]. One of the major structural proteins, the glycoprotein Spike (S) of the SARS-CoV-2 binds to surface receptor (ACE2) of the host cell and mediates viral entry. S protein is composed of two domains; S1 domain contains receptor-binding region, while S2 domain manages viral fusion with the membrane of the host cell. Host transmembrane protease serine type 2 (TMPRSS2) cleaves the S protein into S1 and S2 domains upon virus binding to ACE2 [3–5]. SARS-CoV-2 receptor binding and fusion of viral membrane and cell membrane initiate viral infection.

ACE2 protein is expressed in a variety of human organs and tissues, including ocular tissues ranging from conjunctiva to retina [6, 7]. Understanding the transmission paths of SARS-CoV-2 is crucial to prevent the viral spread. Current studies show that SARS-CoV-2 could be transmitted via direct contact or aerosol droplets. Ocular surfaces are possible viral entry and infection sites, or gateway for spread of the virus to the respiratory system [8, 9]. Although ocular symptoms are rare in COVID-19 patients, manifestations affecting the ocular surfaces such as conjunctivitis, epiphora, chemosis [10, 11], retinal hemorrhages, central retinal vein occlusion (CRVO), ischemia [12–15] as well as blurred vision and vision loss [16, 17] have been reported.

This chapter focuses on the presence and the effects of cellular receptors of SARS-CoV-2 on ocular tissues, evaluates the potential ocular transmission through the eyes, and discusses the short and long-term effects and manifestations of the virus on ocular surfaces at the molecular level.
