Cones and cone pathways remain functional in advanced retinal degeneration

Most defects causing retinal degeneration in retinitis pigmentosa (RP) are rod-specific mutations, but the subsequent degeneration of cones, which produces loss of daylight vision and high-acuity perception, is the most debilitating feature of the disease. To understand better why cones degenerate and how cone vision might be restored, we have made the first single-cell recordings of light responses from degenerating cones and retinal interneurons after most rods have died and cones have lost their outer-segment disk membranes and synaptic pedicles. We show that degenerating cones have functional cyclic-nucleotide-gated channels and can continue to give light responses, apparently produced by opsin localized either to small areas of organized membrane near the ciliary axoneme or distributed throughout the inner segment. Light responses of second-order horizontal and bipolar cells are less sensitive but otherwise resemble those of normal retina. Furthermore, retinal output as reflected in responses of ganglion cells is less sensitive but maintains spatiotemporal receptive fields at cone-mediated light levels. Together, these findings show that cones and their retinal pathways can remain functional even as degeneration is progressing, an encouraging result for future research aimed at enhancing the light sensitivity of residual cones to restore vision in patients with genetically inherited retinal degeneration. •Degenerating cones lose outer segments and synaptic pedicles as if becoming dormant•We show that these cells express cGMP-gated channels and exhibit light-evoked responses•Retinal interneurons and ganglion cells also continue to display vigorous activity•Our results give hope of restoring cone vision in patients with retinal degeneration In retinal degeneration, rods die and cones retract outer segments and synaptic pedicles as if dormant. Ellis et al. show that these cells still express opsin and respond to light with cGMP-gated and voltage-gated channels. The downstream retina also shows vigorous activity, giving new hope of restoring vision in patients with retinal degeneration.