The Roles of Transient Receptor Potential (TRP) Channels Underlying Aberrant Calcium Signaling in Blood-Retinal Barrier Dysfunction

The inner blood-retinal barrier (iBRB) protects the retinal vasculature from the peripheral circulation. Endothelial cells (ECs) are the core component of the iBRB; their close apposition and linkage via tight junctions limit the passage of fluids, proteins, and cells from the bloodstream to the parenchyma. Dysfunction of the iBRB is a hallmark of many retinal disorders. Vascular endothelial growth factor (VEGF) has been identified as the primary driver leading to a dysfunctional iBRB, thereby becoming the main target for therapy. However, a complete understanding of the molecular mechanisms underlying iBRB dysfunction is elusive and alternative therapeutic targets remain unexplored. Calcium (Ca ) is a universal intracellular messenger whose homeostasis and dynamics are dysregulated in many pathological disorders. Among the extensive components of the cellular Ca -signaling toolkit, cation-selective transient receptor potential (TRP) channels are broadly involved in cell physiology and disease and, therefore, are widely studied as possible targets for therapy. Albeit that TRP channels have been discovered in the photoreceptors of and have been studied in the neuroretina, their presence and function in the iBRB have only recently emerged. Within this article, we discuss the structure and functions of the iBRB with a particular focus on Ca signaling in retinal ECs and highlight the potential of TRP channels as new targets for retinal diseases. [Abstract copyright: Copyright © 2024 Cold Spring Harbor Laboratory Press; all rights reserved.]