MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs ...influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D.
We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a
mice.
This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.
Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.
A 72-year-old Chinese male presented with unilateral left eye panuveitis, then diagnosed as bilateral T-cell primary vitreoretinal lymphoma (T-PVRL) through chorioretinal biopsy and ...immunohistochemistry. No CNS nor systemic involvement was found at diagnosis. Despite initiating intravenous and intrathecal chemotherapy and intravitreal methotrexate, the disease eventually spread to the fellow eye with subsequent recurrence and systemic metastasis. To our knowledge, no cases of T-PVRL treated in a silicone-filled eye were reported in the literature. T- PVRL is exceedingly rare, with most PVRL being the malignant B-cell variant. This case highlights the challenges encountered throughout the treatment course of this aggressive entity, including the administration of intravitreal methotrexate in a silicone oil-filled eye. The poor overall survival rate and grim prognosis of T-PVRL are highlighted. Therefore, we recommend prompt tissue biopsy and immediate initiation of systemic chemotherapy and intravitreal methotrexate.
PDF
