Study of the microrna expression profile dysregulation by hydrogen on the retinal pigment epithelium cells: role of mir-205-5p
- Autores: María Oltra Sanchis
- Directores de la Tesis: Jorge Miguel Barcia González (dir. tes.), Francisco Javier Romero Gomez (codir. tes.)
- Lectura: En la Universidad Católica de Valencia San Vicente Mártir ( España ) en 2021
- Idioma: español
- Tribunal Calificador de la Tesis: Antonio Marcilla Díaz (presid.), María Muriach Sauri (secret.), Daniel Bernardo Pérez Cremades (voc.)
- Programa de doctorado: Programa de Doctorado en Ciencias de la Vida y del Medio Natural por la Universidad Católica de Valencia San Vicente Mártir
- Materias:
- Enlaces
- Tesis en acceso abierto en: TESEO
- Resumen
Study of the microRNA expression profile dysregulation by hydrogen peroxide on the retinal pigment epithelium cells: role of miR-205-5p Estudio del perfil de expresión de microRNAs desregulados por el peróxido de hidrógeno en las células de epitelio pigmentario de la retina: papel del miR-205-5p.
Age related macular degeneration (ADM) and diabetic retinopathy (DR) are common retina-related diseases leading to blindness. The retinal pigment epithelium (RPE) is essential for the vision, in fact is well documented that oxidative stress (OS) generated in RPE and choroid neovascularization are related to the origin of these disorders. The study of circulating miRNAs, small non-codding RNA, is opening new possibilities in terms of diagnosis and therapeutics. miRNAs can travel inside small Extracellular Vesicles (sEVs) playing an important role in intracellular communication. Concretely, miR-205-5p is involved in VEGF-related angiogenesis and seems to regulate associated cell signaling pathways.
One of the aims of the present work is to establish a miRNA expression profile of ARPE-19 cells and sEVs released from ARPE-19 cells under oxidative conditions (H2O2). Moreover, we want to evaluate the role of the identified miRNAs and sEVs in the progression of pathological processes related to retinal disorders.
The miRNA expression profile was carried out using SeraMir Profiler that includes 384 miRNAs whose expression was analyzed in ARPE-19 cells and sEVs released by ARPE-19 cells, both in control conditions and treated with 600 mM H2O2 for 24 hours. Additionally, the role of miRNAs and sEVs in angiogenic processes was studied using matrigel assays with HUVEC cells.
We identify a different miRNA expression profile between oxidative stressed and control ARPE-19 cells (Cell miRNAs) and the sEVs (sEV miRNAs) released by them. As a result, 306 out of 384 Cell miRNAs were detected by the array and 7 were significantly over-expressed in H2O2-treated cells. Moreover, 218 miRNAs could be detected in control and H2O2-induced sEVs and only 2 of them were significantly under-expressed in H2O2-induced sEVs. Among the dysregulated Cell miRNAs we found the miR-205-5p. Our results indicate that miR-205-5p is modulated by OS and regulates VEGFA-angiogenesis. We also found the role of 600 mM H2O2-sEVs on oxidative stress induction, cell death increasing and angiogenesis stimulation in healthy ARPE-19 cells.
The miRNA dysregulation observed suggest their implication in retinal disorders after oxidative challenge. Among the dysregulated miRNAs, miR-205-5p is proposed as a candidate against eye-related proliferative diseases. Therefore, results herein suggest the influence of sEV in neighboring cells and the possible utility of sEV miRNAs as biomarkers.
