Cilia-related inherited retinal dystrophy: uncovering fundamental disease mechanism and designing patient-oriented impact

Prof Oliver Blacque and Ms Ailís Moran, University College Dublin

Commencing in 2019, this 3-year project is co-funded by Fighting Blindness and the Irish Research Council (IRC) under the IRC Enterprise Partnership Postgraduate Scheme. Through this study, Prof Blacque and PhD student Ailís Moran aim to unearth important fundamental cilia biology relevant to ciliopathy diseases. We spoke with Prof Blacque to learn a little more.

Can you tell us a little more about your research project?

A few years ago, through studying the ‘eyeless’ nematode worm (C. elegans), our lab discovered that that a protein called Rab28 operates in a type of cilia called the primary cilia. Since then, we and others groups have shown that, in mice and zebrafish, this Rab28 protein functions in the photoreceptor cell’s outer segment (modified cilium). Cilia are slender, microscopic, hair-like structures that extend from the surface of nearly all mammalian cells, including retinal cells.

They act like microscopic train-tracks, and allow the transport of vital molecules from one end of the photoreceptor to the other. Dysfunction or defects in cilia are now understood to underlie a number of genetic forms of retina conditions such as cone-rod dystrophy, Usher syndrome, Bardet-Biedel syndrome and Alström Syndrome. Collectively, these are termed ciliopathies. However, despite progress, we still know very little about what exactly Rab28 is doing in cilia, how its function relates to ciliopathy proteins, and how its disruption causes blindness.

This project aims to increase our understanding of Rab28 and potential role in cone-rod dystrophy. In addition, together with Fighting Blindness, this project will develop patient-oriented strategies towards greater public awareness and engagement of ciliopathy-related IRDs.

What attracted you to retinal research?

During my postdoctoral research, I worked on a ciliopathy disorder called Bardet-Biedl syndrome (BBS). Thus, from the outset, I was interested in the role that cilia play in the retina. On arriving at UCD, there were a number of groups there studying retinal research which again encouraged me.

Retinal research is also particularly attractive to me because of the emerging notion that therapeutic endpoints can be achieved by uncovering the secrets of cilium biology.

Within the next five years, where do you expect great advances to be made in vision research?

Gene editing techniques that precisely engineer patient mutations in animal models represents a paradigm shift towards better understanding of disease mechanisms and routes to therapy.

What are your other interests?

I am broadly interested in understanding the fundamental mechanisms by which primary cilia are built and maintained, including how molecular barriers at the base of cilia control the entry and exit of molecules into the structure.