Do Extracellular RNAs Provide Insight into Uveal Melanoma Biology?

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, showing a high mortality due to metastasis. Although it is considered a rare disease, a growing number of papers have reported altered levels of RNAs (i.e., coding and non-coding RNAs) in cancerous tissues and biological fluids from UM patients. The presence of circulating RNAs, whose dysregulation is associated with UM, paved the way to the possibility of exploiting it for diagnostic and prognostic purposes. However, the biological meaning and the origin of such RNAs in blood and ocular fluids of UM patients remain unexplored. In this review, we report the state of the art of circulating RNAs in UM and debate whether the amount and types of RNAs measured in bodily fluids mirror the RNA alterations from source cancer cells. Based on literature data, extracellular RNAs in UM patients do not represent, with rare exceptions, a snapshot of RNA dysregulations occurring in cancerous tissues, but rather the complex and heterogeneous outcome of a systemic dysfunction, including immune system activity, that modifies the mechanisms of RNA delivery from several cell types.

Do Ocular Fluids Represent a Transmission Route of SARS-CoV-2 Infection?

The spread of the new SARS-CoV-2 is marked by a short timeline. In this scenario, explaining or excluding the possible transmission routes is mandatory to contain and manage the spread of the disease in the community. In the recent pandemic, it is still unclear how coronavirus can end up in ocular fluids. Nevertheless, eye redness and irritation in COVID-19 patients have been reported, suggesting that a possible ocular manifestation of SARS-CoV-2 infection may be conjunctivitis. On the basis of epidemiological data provided by previous SARS-Cove infection, numerous theories have been proposed: (1) conjunctiva as the site of direct inoculation by infected droplets; (2) the nasolacrimal duct as a migration route of the virus to the upper respiratory tract, or (3) haematogenic infection of the tear gland. The demand for further investigations to verify ocular involvement in COVID-19 infection came out from the results of recent meta-analysis studies, so the eye cannot be completely excluded as a transmission route of the infection. Thus, healthcare personnel and all the people that enter in contact with infected or suspected patients must always use the prescribed protective equipment.

Protein Biomarkers in Uveitis

The diseases affecting the retina or uvea (iris, ciliary body, or choroid) generate changes in the biochemical or protein composition of ocular fluids/tissues due to disruption of blood-retinal barrier. Ocular infections and inflammations are sight-threatening diseases associated with various infectious and non-infectious etiologies. Several etiological entities cause uveitis, a complex intraocular inflammatory disease. These causes of uveitis differ in different populations due to geographical, racial, and socioeconomic variations. While clinical appearance is sufficiently diagnostic in many diseases, some of the uveitic entities manifest nonspecific or atypical clinical presentation. Identification of biomarkers in such diseases is an important aid in their diagnostic armamentarium. Different diseases and their different severity states release varying concentrations of proteins, which can serve as biomarkers. Proteomics is a high throughput technology and a powerful screening tool for serum biomarkers in various diseases that identifies proteins by mass spectrometry and helps to improve the understanding of pathogenesis of a disease. Proteins determine the biological state of a cell. Once identified as biomarkers, they serve as future diagnostic and pharmaceutical targets. With a potential to redirect the diagnosis of idiopathic uveitis, ocular proteomics provide a new insight into the pathophysiology and therapeutics of various ocular inflammatory diseases. Tears, aqueous and vitreous humor represent potential repositories for proteomic biomarkers discovery in uveitis. With an extensive proteomics work done on animal models of uveitis, various types of human uveitis are being subjected to proteome analysis for biomarker discovery in different ocular fluids (vitreous, aqueous, or tears).

Viral Loads in Ocular Fluids of Acute Retinal Necrosis Eyes Infected by Varicella-Zoster Virus Treated with Intravenous Acyclovir Treatment

Acute retinal necrosis (ARN) is a rare viral endophthalmitis, and human herpesvirus is the principal pathogen. Early diagnosis and treatment are critical to avoid visual impairment by ARN, and pars plana vitrectomy (PPV) is required in advanced cases. In this study, we evaluated the transition of viral load in ocular fluids of ARN eyes with varicella-zoster virus (VZV) after intravenous acyclovir treatment. Fourteen eyes of 13 patients were analyzed retrospectively. All patients received intravenous acyclovir treatment, and eventually, all eyes underwent PPV. A polymerase chain reaction (PCR) test showed a 100% detection rate in all aqueous humor samples collected before the treatment (Pre-AH), as well as aqueous humor (Post-AH) and vitreous fluid samples (VF), collected during PPV conducted after the treatment. Within eight days or less of acyclovir treatment, viral loads both in AH and VF did not decrease significantly. Furthermore, the viral load of Pre-AH had a strong correlation with that of VH. These data suggest that in ARN eyes with VZV infection, the AH sample for the PCR test was reliable to confirm the pathogen. We propose that short-term treatment of intravenous acyclovir may be insufficient for reducing intraocular viral load, and the Pre-AH sample could be a predictor of viral activity in the eyes after acyclovir treatment.