Abstract
Purpose:
Retinitis pigmentosa (RP) encompasses a wide range of diseases resulting in photoreceptor degeneration and progressive blindness with no available cure. A small number of intrinsically photosensitive Retinal Ganglion Cells (ipRGCs) which express the photopigment melanopsin survive retinal degeneration and directly innervate visual processing structures including the dorsal lateral geniculate nucleus (dLGN). Although patients with advanced retinal degeneration may retain some awareness of light they lack spatial discrimination. This limit of melanopsin’s ability to support spatial vision could reflect multiple aspects of its physiology, but one possibility that has not been addressed is that it is attributable to a fundamental loss of spatial structure in the information reaching the dLGN thanks to disruptive organisation of retinal projections.
Methods:
We use in-vitro and in-vivo extracellular recordings to map receptive fields of ipRGCs in the retina and their target neurones in the lateral geniculate nucleus of rd/cl C3H mice, homozygous for the rd1 mutation and carrying an additional diphtheria-based lesion of cone photoreceptors to produce a model of advanced retinal degeneration.
Results:
We demonstrate that melanopsin-driven neurones in the retina and LGN possess simple receptive fields that can be adequately described by a Gaussian function. ipRGCs possess receptive fields ranging from 8.9° - 30°. Contrastingly, LGN neurones have significantly larger receptive fields ranging from 18° - 90°, but most are around 30° - 50°, which is the size predicted for a cell receiving input from 1-3 ipRGCs in neighbouring parts of the retina. Consistent with this view, we find that these inputs match the retinotopic organisation reported for mice.
Conclusions:
This data reveals that crude spatial discrimination could be possible with ipRGCs, and identifies the poor temporal kinetics of melanopsin signalling as the more significant limitation to its contribution to spatial vision in advanced retinal degeneration. They further confirm that at least some Ganglion Cell projections remain ordered in advanced retinal degeneration.