A Survey of Multigenic Protein-Altering Variant Frequency in Familial Exudative Vitreo-Retinopathy (FEVR) Patients by Targeted Sequencing of Seven FEVR-Linked Genes.

While Inherited Retinal Diseases (IRDs) are typically considered rare diseases, Familial Exudative Vitreo-Retinopathy (FEVR) and Norrie Disease (ND) are more rare than retinitis pigmentosa. We wanted to determine if multigenic protein-altering variants are common in FEVR subjects within a set of FEVR-related genes. The potential occurrence of protein-altering variants in two different genes has been documented in a very small percentage of patients, but potential multigenic contributions to FEVR remain unclear.

Differences in activation of intracellular signaling in primary human retinal endothelial cells between isoforms of VEGFA 165.

Purpose: There are reports that a b-isoform of vascular endothelial growth factor-A 165 (VEGFAb) is predominant in normal human vitreous, switching to the a-isoform (VEGFAa) in the vitreous of some diseased eyes. Although these isoforms appear to have a different ability to activate the VEGF receptor 2 (VEGFR2) in various endothelial cells, the nature of their ability to activate intracellular signaling pathways is not fully characterized, especially in retinal endothelial cells. We determined their activation potential for two key intracellular signaling pathways (MAPK, AKT) over complete dose-response curves and compared potential effects on the expression of several VEGFA target genes in primary human retinal microvascular endothelial cells (HRMECs).