Fig. 4. LRG1 vasculopathic effects.

A mature functional vessel is characterised by extensive pericyte coverage of the endothelium, and tight junctions between adjacent ECs to maintain barrier function. Confocal 3D reconstruction of murine retina showing high pericyte (yellow) coverage of ECs (magenta). In homoeostatic conditions, LRG1 is found at low levels in the circulation and is undetectable in the retinal tissue. In pathological scenarios, such as nvAMD and DR, LRG1 is upregulated both locally and systemically and contributes to vascular instability by altering pericyte-EC interactions and by directly promoting EC activation. These pathological alterations can result in loss of vessel homoeostatic function (i.e. barrier properties) and ultimately lead to the growth of new pathological vessels. Created with BioRender.com.