Project A.22

Retinal diseases arise from degeneration of photoreceptor cells, whose preservation depends on the Retinal Pigment Epithelium (RPE). RPE cell function is ensured by the primary cilium, a cell organelle found at the cell membrane of almost all vertebrate cells. Acting as a signalling hub, it regulates the release of Extracellular Vesicles (EV). My research investigates how the primary cilium in RPE cells regulates EV release to understand how ciliary signalling contributes to vision.

Visual impairment is becoming an increasingly common and serious health problem, as the world's population grows and more people reach an advanced age.

Among the leading causes of vision loss are retinal diseases, which primarily result from dysfunction and degeneration of photoreceptor cells.  The maintenance of Photoreceptor cells is the key function of the Retinal Pigment Epithelium (RPE). The RPE forms a polarized monolayer of cells positioned between the neural retina and the choroidal blood supply, playing a fundamental role in maintaining retinal structure and function.​

RPE cell activity is closely linked to the primary cilium, a microtubule-based organelle found at the membrane of nearly all vertebrate cells. This organelle acts as a signalling hub and is essential for maintaining cellular functions. Ciliary signalling is through specialized proteins responsible for cargo transport along the axoneme, receptor enrichment in the ciliary membrane and vesicular trafficking. The formation of vesicles is an evolutionary conserved process important for cellular homeostasis and functionality. As part of vesicular trafficking, cells release vesicles via fusion with the plasma membrane which gives rise to Extracellular Vesicles (EVs).

Mutations in genes necessary for ciliary structure or function can cause ciliopathies, a group of syndromes that all share vision impairment as one of the most common phenotypes. To address the underlying mechanisms of retinal functionality, my research aims to elucidate the role of the primary cilium in regulating the release of extracellular vesicles from RPE cells, thereby improving our understanding of how the primary cilium contributes to the maintenance or loss of vision.