Tear-derived exosomal biomarkers of Graves’ ophthalmopathy

Abstract

Graves’ ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves’ disease (GD), can lead to a significant decline in the quality of life in patients. Exosomes, which contain proteins, lipids and DNA, play important roles in the pathological processes of various diseases. However, their roles in Graves’ ophthalmopathy are still unclear. We aimed to isolate exosomes and analyze the different exosomal proteins. Tear fluids were collected from twenty-four GO patients, twenty-four GD patients and sixteen control subjects. The numbers of tear exosomes were assayed using nanoparticle tracking analysis. A Luminex 200 kit and ELISA kit were used to confirm the different cytokine concentrations in serum. Extraocular muscle from GO patients and controls was extracted, and western blotting was used to assay the levels of Caspase-3 and complement C4A. Our study demonstrated that the number of tear exosomes differ from GD patients and control. The expression levels of cytokines, including IL-1 and IL-18, were significantly increased in the tear exosomes and serum from GO patients compared with GD patients and controls. The levels of the exosomal proteins Caspase-3, complement C4A and APOA-IV were significantly increased in GO patients compared to GD patients and controls. Orbital fibroblasts from GO patients showed significantly higher levels of Caspase-3 and complement C4A than those from controls. The levels of serum APOA-IV in GO patients were significantly higher than those in GD patients and controls. Specific proteins showed elevated expression in tear exosomes from GO patients, indicating that they may play important roles in GO pathogenesis.

Molecular Biomarkers in Thyroid Eye Disease: A Literature Review

“…A more recent study from 2022 reported that patients with GD and active TED had elevated levels of caspase-3, complement C4A, and apolipoprotein A-IV, compared with those without TED. 73 Caspase-3 has been related to apoptosis. Complement C4A (from the classic complement pathway) is essential in local inflammation.…”

“…72 A more recent study from 2022 reported that patients with GD and active TED had elevated levels of caspase-3, complement C4A, and apolipoprotein A-IV, compared with those without TED. 73 Caspase-3…”

From biogenesis to aptasensors: advancements in analysis for tumor-derived extracellular vesicles research

“…One such challenge is the requirement for distinct processing procedures for EV samples derived from different body fluids (Figure 3 ) 30 . EVs are demonstrated that presented in almost all the body fluids including cell culture-conditioned media 31 - 35 , blood/serum/plasma 36 - 40 , pleural effusions and ascites 41 - 44 , saliva 45 - 48 , urine 49 - 55 , tear fluid 56 - 59 , and cerebrospinal fluid (CSF) 60 - 63 . The concentration, composition, and bioactivities of EVs can vary significantly depending on the type of body fluid, collection strategies, storage conditions, and pretreatment methods 64 , 65 .…”

Tear exosomes: A messenger of clinical health complication

“…These findings underscore the potential involvement of tear exosomes in the pathogenesis of GO, marked by elevated levels of cytokines such as IL-1β, IL-8 and IL-13, as well as notable proteins like Caspase-3, C4A and APOA-IV. 11 There is a compelling association between tear exosomes and the pathogenesis of Herpes Stromal Keratitis induced by Herpes Simplex Virus-1. Corneal exosomal microRNA proteins finely tune the response to bacterial infection by influencing corneal innervation and innate immunity.…”