All eukaryotic mRNAs (except organellar) are capped at their 5 end. The cap structure (m 7 GpppN, where N is any nucleotide) is extremely important for the processing and translation of mRNA. Several cap-binding proteins that facilitate these processes have been characterized. Here we describe a novel human cytoplasmic protein that is 30% identical and 60% similar to the human translation initiation factor 4E (eIF4E). We demonstrate that this protein, named 4E Homologous Protein (4EHP), binds specifically to capped RNA in an ATP-and divalent ion-independent manner. The three-dimensional structure of 4EHP, as predicted by homology modeling, closely resembles that of eIF4E and site-directed mutagenesis analysis of 4EHP strongly suggests that it shares with eIF4E a common mechanism for cap binding. A putative function for 4EHP is discussed.
IS/OS and ELM are useful hallmarks for use in evaluation of foveal photoreceptor layer integrity, and are closely associated with final VA in DME. Pretreatment VA and photoreceptor status can predict potential restoration of photoreceptor integrity and subsequent visual recovery in DME.
Vessel tortuosity increased as the stage of NPDR was more severe, but decreased in PDR. The vessel tortuosity determined using optical coherence tomography angiography might be a useful parameter indicating the progression to PDR, circumventing the risk from invasive conventional angiography.
Age-related macular degeneration (AMD) describes the progressive degeneration of the retinal pigment epithelium (RPE), retina, and choriocapillaris and is the leading cause of blindness in people over 50. The molecular mechanisms underlying this multifactorial disease remain largely unknown. To uncover novel secretory biomarkers related to the pathogenesis of AMD, we adopted an integrated approach to compare the proteins identified in the conditioned medium (CM) of cultured RPE cells and the exosomes derived from CM and from the aqueous humor (AH) of AMD patients by LC-ESI-MS/MS. Finally, LC-MRM was performed on the AH from patients and controls, which revealed that cathepsin D, cytokeratin 8, and four other proteins increased in the AH of AMD patients. The present study has identified potential biomarkers and therapeutic targets for AMD treatment, such as proteins related to the autophagy-lysosomal pathway and epithelial-mesenchymal transition, and demonstrated a novel and effective approach to identifying AMD-associated proteins that might be secreted by RPE in vivo in the form of exosomes. The proteomics-based characterization of this multifactorial disease could help to match a particular marker to particular target-based therapy in AMD patients with various phenotypes.
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