He noted there is analogous anatomy in the eye where aquaporin-4 channels in Mueller cells control fluid flow in and out of the blood vessels.
“Current approaches to treating ME focus on modulating leakage from blood vessels. Perhaps targeting the Mueller cells and their aquaporin channels may be a better strategy for fluid removal,” Dr. Spaide said.
He proposed a pathway for the development of ME and damage to the deep vascular layer taking into account the watertightness of the external limiting membrane relative to the inner limiting membrane, the characteristics of vessels in the different layers, and the effects of ischemia-induced chemical mediators on hydrostatic pressure and vascular occlusion.
Based on Starling’s law, one would predict fluid would flow from the inner portion of the retina to the deeper layer, Dr. Spaide said.
When vascular occlusion and regional ischemia develop, cytokines, growth factors, and chemokines are released that increase hydrostatic pressure and leakage from the inner retina.
The chemical milieu also includes cytokines that increase expression of intercellular adhesion molecule-1 on small blood vessels and VEGF, which induces intravascular endothelial cell proliferation, resulting in vascular occlusion.
The impact of this cascade would be greater in the deeper vascular plexus where the entire network of vessels are capillary-sized versus in the inner plexus where capillaries represent only one small segment of the vasculature.
“We would expect greater damage to the deep plexus vessels that would account for the flow void,” Dr. Spaide said. “In the absence of deep plexus flow, there is no way to pump out the fluid, and it would accumulate as edema.”
Richard F. Spaide, MD