Functional cone rescue by RdCVF protein in a dominant model of retinitis pigmentosa

In retinitis pigmentosa (RP), a majority of causative mutations affect genes solely expressed in rods; however, cone degeneration inevitably follows rod cell loss. Following transplantation and in vitro studies, we demonstrated the role of photoreceptor cell paracrine interactions and identified a Rod-derived Cone Viability Factor (RdCVF), which increases cone survival. In order to establish the clinical relevance of such mechanism, we assessed the functional benefit afforded by the injection of this factor in a frequent type of rhodopsin mutation, the P23H rat. In this model of autosomal dominant RP, RdCVF expression decreases in parallel with primary rod degeneration, which is followed by cone loss. RdCVF protein injections induced an increase in cone cell number and, more important, a further increase in the corresponding electroretinogram (ERG). These results indicate that RdCVF can not only rescue cones but also preserve significantly their function. Interestingly, the higher amplitude of the functional versus the survival effect of RdCVF on cones indicates that RdCVF is acting more directly on cone function. The demonstration at the functional level of the therapeutic potential of RdCVF in the most frequent of dominant RP mutations paves the way toward the use of RdCVF for preserving central vision in many RP patients.