An eye on cone outer segments

The retinal degeneration slow (Rds) gene is required in rod photoreceptor cells for morphogenesis of outer segments (OSs) and cell survival. On page 59, Farjo et al. report that cone photoreceptor cells also develop abnormal OS structures in the absence of Rds, but they remain functional, suggesting that the protein may have different roles in the two cell types and hinting at ways to treat some degenerative eye disorders in humans.

Rods constitute more than 95% of the photoreceptor population in rodent retina, making the structure an imperfect model for the central portion of the human retina, called the macula, which is composed mostly of cones and is largely responsible for visual acuity. Recently, researchers created a knock-out mouse, Nrl^−/−, in which rod progenitor cells are transformed into cones, enabling researchers to study cone cell formation and function in the absence of rods.

In the retina of double knock-out animals lacking both Nrl and Rds, cones are capable of phototransduction, albeit at about one log lower sensitivity than cone cells in Nrl^−/− animals that retain functional Rds. Cone OSs in the double mutant are misshapen and lack the regularly stacked lamellae that occur in wild-type cones. Instead the cones form distended, tubular OS structures.

Rds is not vital for cone formation or function; however, mutations in the gene are associated with rod and cone defects in humans, including macular dystrophy. Farjo et al. think that having no Rds may be better than having the mutant protein. If that is true, then RNAi treatment designed to eliminate Rds protein in cones may allow rudimentary OS formation and improve a person's vision. To find out, the team has already moved one of the common human Rds mutations into the Nrl knock-out strain where they can examine its impact on cones and test whether RNAi can rescue the retina from degeneration and dysfunction.