Claire Konstantopoulou1, Dimitrios Roukas2, Paraskevi Tziakou3, Evangelos Tsiambas4
1Dept of Ophthalmology, 417 VA Hospital (NIMTS), Athens, Greece.
2Department of Psychiatry, 417 VA Hospital (NIMTS), Athens, Greece.
3Department of Pathology, “Thriasio” General Hospital, Elefsina, Greece.
4Department of Cytology, 417 VA Hospital (NIMTS), Athens, Greece.
Abstract
Dear Editor,
Intraocular malignancies are rare in childhood, and for this reason early diagnosis and early treatment implementation modifies positively the prognosis of the corresponding patients. Among them, retinoblastoma (Rb) -although the most common primary malignant intraocular carcinoma in children- is a rare type developed histo-pathologically by abnormal immature cells of retina, the light-detecting tissue of the eye responsible for light and color recognition. Concerning its genetic signature, Rb suppressor gene demonstrates a sporadic and also hereditary (germinal) pattern caused by a congenital mutation in the chromosome 13 gene 13q14 (retinoblastoma protein). It seems – as it happens in other malignancies including breast and pancreatic carcinoma- that pandemics like coronavirus-related have negatively influenced the management of a variety of oncological patients [1,2]. Specific studies on retinoblastoma patients have concluded that delay in optimal and timely management leads to prolonged treatment interruptions, permanent default, and even death in children, especially in countries with vast, uncontrolled populations [3]. Coronavirus-related severe acute respiratory syndrome (SARS-CoV) in 2002/2003, Middle-East respiratory syndrome (MERSCoV) in 2012/2013, and especially the current 2019/2020 severe acute respiratory syndrome-2 (SARS-CoV-2) affected negatively the national health systems’ endurance worldwide. SARS-Cov-2 virus belongs to lineage b of beta-CoVs, demonstrating a strong phylogenetic similarity with BatCoVRaTG13 type. Concerning its genomic structure, a large non-segmented, positive-sense RNA molecule of approximately 30 kb has been detected and analyzed in conjunction with the corresponding RNA-dependent RNA-polymerase (Rd-Rp) that is essential for its replication in the cytoplasm of the target epithelial cells. Analyzing SARS-CoV-2 spherical virion’s structure (diam~100nm), research groups have confirmed that there are four main proteins including the spike surface glycoprotein (S), the main or matrix protein (M), the envelope protein (E), and finally the nucleocapsid protein (NC). S glycoprotein projections -consisting of two subunits S1/S2- provide a unique crown-like formation (corona) on the virion’s surface. Concerning their functional role, S1 represents the main receptor-binding domain (RBD), whereas S2 is involved in the virus-cell membrane fusion mechanism interacting with proteases, such as furin, thrypsin, cathepsin or serino-protease TMPRSS2. SARS-CoV-2 molecular basis is under investigation by implementing novel, sophisticated multi-omics based techniques. Concerning the influence of SARS-CoVs’ specific genomic sequences in Rb gene, some molecular studies have already revealed crucial interactions with an endoribonuclease, the Nsp15 [4]. An in vitro analysis showed that retinoblastoma protein-binding motif (LXCXE/D) exists in the majority of Nsp15 altered cases of severe acute respiratory syndromes mediated by Covs. Additionally, mutations in the Rb-binding motif modify the corresponding expression of the sNsp15 in cells leading to an increased abundance of Rb in the cytoplasm, but also decrease overall levels of Rb. Similarly, SARS-CoVs’ well conserved open reading frames (ORFs) are involved in Rb abnormal expression. A molecular study showed that ORF7a overexpression down regulated the mRNA transcription and expression of cyclin D3 leading to decreased activity of cyclin D/cdk4/6 by inhibiting Rb phosphorylation. These aberrations block cell cycle progression at G0/G1 phase.
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