The research entitled "Biochemical-molecular-genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients" was carried out with the participation of Dr. Vicente Zanón Moreno, professor at the International University of Valencia - VIU and researcher at the Institute of Biosanitary Research of VIU (IIB-VIU). Also, Dr. Mª Dolores Pinazo Durán and Dr. Irene Andrés Blasco, collaborators of the research group in Clinical, Genetics, Epigenetics and Molecular Epidemiology (ECLIGEM) of the IIB-VIU have participated in this project.
Glaucoma is a chronic neurodegenerative disease and one of the leading causes of irreversible blindness worldwide. There are different types of glaucoma, being the primary open-angle glaucoma (POAG) the most frequent. This type of glaucoma is characterized by elevated intraocular pressure, optic nerve atrophy and visual field loss. There is no cure for this disease,so the early diagnosis is essential to prevent its progression to blindness.
The researchers have analyzed tear, aqueous humor, plasma and blood samples from 358 patients with POAG and 226 healthy subjects (controls) or with cataracts (comparative group). These samples were analyzed to study different processes and alterations in relation to POAG, such as inflammatory processes, oxidative stress, endothelial dysfunction, alteration of neurotransmitters and neurotrophins, gene expression and expression of microRNAs. The data obtained were processed by bioinformatics and statistical analysis.
Significantly higher concentrations of interleukin 6 (IL6), nitric oxide, malondialdehyde and 5-hydroxyindolacetic acid and lower concentrations of brain-derived neurotrophic factor (BDNF) as well as significantly lower total antioxidant capacity were found in aqueous humor of glaucoma patients compared to subjects with cataracts.
In plasma samples, significantly higher levels of IL6 and lower levels of serotonin were observed in patients with POAG compared to levels observed in control subjects.
The results observed after analysis of tear samples evidenced significantly higher concentrations of IL6 in patients with POAG, as well as over-expression of miRNAs 26b-5p, 30e-5p and 152-3p and under-expression of miRNA 151a-3p in patients with POAG.
Finally, significantly lower expression of SLC23A2 and GPX4 genes was observed in glaucoma.
Regarding the different biological samples analyzed, we have found that tears are an ideal biological fluid for the study of clinical biomarkers, since they are painless and non-invasive to obtain, and the collection method is easy to carry out, both by ophthalmologists and by nurses. Therefore, it is an optimal sample for the identification of biochemical, molecular and genetic biomarkers related to ocular pathologies.
The present study has allowed the identification of several potential biomarker candidates related to the genetics of POAG and some of the main pathogenic mechanisms of POAG: oxidative stress and inflammation. These potential biomarkers, mainly those based on microRNAs, could be used for the design and development of new therapies to facilitate the prevention of irreversible blindness caused by this optic neuropathy.
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