The roles of Transient Receptor Potential (TRP) channels and aberrant calcium signalling in blood-retinal barrier dysfunction

Dragoni, Silvia; Moccia, Francesco and Bootman, Martin D. (2023). The roles of Transient Receptor Potential (TRP) channels and aberrant calcium signalling in blood-retinal barrier dysfunction. Communications Biology [Submitted to]

Abstract

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 is a universal cellular messenger whose homeostasis is dysregulated in many pathological disorders. Among the extensive components of the cellular calcium signalling 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 Drosophila and have been studied in the neuroretina, not much is known about their expression and function in the iBRB. Within this article, we discuss the structure and functions of the iBRB with a particular focus on calcium signalling in retinal ECs and highlight the potential of TRP channels as new targets for retinal diseases.

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