NOS3 and snowflake vitreoretinal degeneration: EC dysfunction can be defined by several molecular signatures that parallel the microvascular dysfunctions observed macroscopically in human SVD, including loss of eNOS indicating less NO production, reduction in CLDN5 tight junction protein indicating loss of BBB integrity, and an upregulation in activation markers, such as Intercellular Adhesion Molecule 1 (ICAM-1) [6, 24, 62].