In the course of retinopathy pigmentosa, the sequence of events linked to mutations expressed in specific rod cell proteins, responsible for night vision, leads secondarily to cone degeneration, resulting in the loss of central vision, color vision and day vision. This is the main event leading to blindness. As this event is largely independent of the causal mutation, it seems logical to target a therapeutic approach on this phase of the disease's evolution, which could make it possible to treat the majority of patients, independently of the causal mutation, while implementing this therapeutic approach at more advanced stages of the condition.
We considered several hypotheses linking rod and cone degeneration. These hypotheses have been systematically tested, enabling us to demonstrate the existence of a trophic interaction between rod and cone cells, using transplantation experiments, then co-cultures and biochemistry.
This demonstration then led to a systematic strategy for identifying cone survival factors, which in 2004 led to the characterization of the rod-derived cone viability factor (RdCVF). This factor comprises two alternatively spliced variants, corresponding to two types of function: an antioxidant function belonging to the thioredoxin family, and a trophic function via paracrine interaction. This family of trophic factors is called nucleoredoxin-like protein and comprises two genes to date, one discovered by our expression-based cloning strategy, the other in silico.
