Affecting over one million people worldwide, the genetic disease 'Retinitis Pigmentosa' (RP) stems from the degeneration of photorecep­tors. These are specialised neuronal cells in the eye capable of transducing light into a signal to the brain. In RP, rod photoreceptors that are responsible for night vision degenerate first, fol­lowed by cones, which mediate daytime vision.

Saving cones

The protein ‘Rod-derived cone viability factor’ (RdCVF) is expressed and secreted by rod photoreceptors. RdCVF sus­tains the viability of cone photorecep­tors. The protein has been shown experimentally to correct RP. Given that even only 5 % of functional cones pro­vide substantial vision, the EU-funded RDCVF project proposed to administer RdCVF as a therapy against the secondary degeneration of cones in RP.

Technical hurdles

In order to achieve clinical applicabil­ity, the consortium had to ensure that it was able to produce manufac­turing-level RdCVF protein in cell lines. For this purpose, they developed analytical methods and specific polyclonal antibodies. In addition, the partners established a cul­ture system from chick embryos. This enabled them to assess the outcome of RdCVF treatment in terms of cone photoreceptor cell viability. Assays for evaluating the impact of RdCVF protein in vivo were also set up, including an automated cone counting system that measured cone density by scanning the retinal surface. Unfortunately, the hydrophobic nature of the RdCVF protein hampered its scalable pro­duction and purification using stand­ard methods.

Conclusion

RdCVF protein administration as a therapy for RP has enormous potential provided its clinical-grade production overcomes certain technical hurdles. The pharmacological, pharmacokinet­ics and toxicological studies proposed by the RDCVF study should still pave the way to a protein therapy.

 

This article was adapted from the September 2014 issue of Research.eu magazine. Read more about European efforts to fight eye diseases on the www.HorizonHealth.eu project pages of OPTISTEM and EUROCONDOR.