The Retinal Relaxing Factor: Update on an Enigmatic Regulator of the Retinal Circulation

Abstract

The retinal circulation is regulated by different local factors and might include the retinal relaxing factor (RRF). This factor is found to be continuously released by the retina and relaxes smooth muscle cells. This review describes the current knowledge about the RRF. Despite many research efforts, the cellular source, identity, mechanism, and physiological role of the RRF remain largely unknown. Thus far, it seems that the RRF is a hydrophilic, thermostable, diffusible chemical messenger, which characteristics do not correspond with most well-known endogenous vasorelaxants. The RRF-induced relaxation seems to rely on activation of the inward rectifier K+ channels and the Rho kinase Ca2+ sensitization mechanism. Voltage-dependent K+ channels and plasma membrane Ca2+-ATPase might also be involved, whereas the involvement of cyclooxygenase is still a point of discussion. Furthermore, it appears that the RRF is involved in other relaxation pathways, namely those of hypoxia, adenosine, and adenosine triphosphate, hydrogen sulfide, γ-aminobutyric acid, and dorzolamide.

Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies

“…The outer half of the retina, rich in oxidative enzymes and containing the photoreceptors, is supplied by the choroidal circulation with blood. Choroidal blood vessels are regulated by the sympathetic and parasympathetic nervous systems [ 31 , 33 ]. Although the retina is in high demand for oxidative metabolism, it needs to maintain transparency as a visually conductive tissue and therefore has a particularly low density of blood vessels [ 34 ].…”