Recent findings suggesting that cones depend on rods for survival may provide a basis for the protection of non-functioning rods in patients with rod-cone dystrophies.Early intervention with neuroprotective treatments has been considered an important component in the preservation of photoreceptor cells in patients with rod-cone dystrophies. Neuroprotective treatments have traditionally been used to protect photoreceptor functioning. However, the scope of neuroprotective strategies may change as the relationships involved in rod-cone cell signalling are better understood.
Most retinal dystrophies are rod-cone distraught cone dystrophies, meaning that patients first lose darkened and peripheral vision. The main concern for patients is that the pathway for cone photoreceptor degeneration cannot be explained. Even a small proportion of functioning cones is sufficient for major visual function, making the preservation of cones essential.¹
Neuroprotection has been accepted as a way to protect photoreceptors in retinal dystrophies. "Neuroprotection of photoreceptor cells in rod-cone degenerations is primarily targeted at preventing the loss of function." This target may shift as previously unknown factors in neuronal signalling are identified.¹

According to various studies, loss of cones is the key event leading to blindness in patients with rod-cone dystrophies (blindness refers to both central and peripheral vision). In studies using mouse models and in patient studies, it has been found that cone cell death lags behind rod cell death until all cones are depleted.²

Observation of the period, when cone cell death lags behind rod cell death, may reveal the relationship between these two. Because the secondary degeneration of cones is the main event leading to profound visual impairment, an understanding of the cone-rod relationship is vital to preserving both cones and rods.²

Dr. Sahel and colleagues studied the possibility of atrophic support using a mouse model. Normal photoreceptor cells were transplanted into the mouse model, so that cone survival can be observed after transplanting rod photoreceptors. Despite the fact that the number of photoreceptor cells transplanted was small, cone survival was increased. Results supported the theory that cones need rods to survive.²

Dr. Sahel and colleagues postulated that the absence of rod-derived cone viability factors induce cone cell trophic deprivation that leads to secondary loss of cones. A total of 200,000 clones were screened until one specific rod-derived cone viability factor was isolated. This factor was found to be a novel protein belonging to the thioredoxin-like family.³

The mode of action for this factor, as well as its effect on other models, will now be explored, so that the rod-derived cone viability factor and its effect on cone survival can be examined in further clinical trials. These findings may result in the development of cone-saving strategies.³

"This is a relevant strategy for promoting cone survival and protecting vision in patients," Dr. Sahel said. "Preserving cones would prevent 1.5 million people from becoming blind."³

The relationship between neuronal interactions is revealing new ways to focus neuroprotective strategies in rod-cone dystrophies. Unknown factors in neuronal signalling may also have future implications in neuroprotective strategies in diseases such as glaucoma, but further research is required.