Purchase this article with an account.
Frederick R. Blodi, Steven F. Stasheff, Stewart Thompson, Malini Shankar, Robert F. Mullins, Michael P. Andrews, Edwin M. Stone; More Numerous Photosensitive Ganglion Cells In A Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4338.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We sought to determine the origin of increased behavioral sensitivity to light in a mouse model of the inherited early-onset macular degenerative disease malattia leventinese (Efemp1R345W) . We previously found that this mutation caused an unexpected increase in sensitivity to light for a behavior (negative masking) mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs) . Next, we determined that Efemp1 localizes to the retinal ganglion cell layer, and hypothesized that mutant Efemp1 was altering the light responsiveness of retinal ganglion cells. We now report an increased number of ipRGC-like responses in Efemp1R345W mice.
We used in vitro multielectrode recording to monitor retinal ganglion cell activity in wild type (wt) and Efemp1R345W mice. Action potentials were recorded as full field broadband light flashes were presented (peak irradiance 1016-1018 photons/cm2·s at 548 nm, duration 2-25 sec) to retinas perfused with control Ringer’s solution and one designed to pharmacologically prevent all synaptic transmission, thus revealing those cells with intrinsic photosensitivity.
In wt retinas under pharmacologic blockade of synaptic transmission, typically 3-4 ganglion cells per retina were detected that had responses characteristic of ipRGCs (relatively long latency and duration). In contrast, 15-25 such cells were recorded in retinas from Efemp1R345W mice.
Our recordings indicate that Efemp1R345W mutations can lead to an increase in the number of ganglion cells that exhibit intrinsic responses to light. This might be due to an overall greater number of melanopsin-containing ipRGCs in mutant retinas relative to wt. Alternatively, there may be increased signal propagation from ipRGCs to other classes of ganglion cells not normally directly responsive to light. In either case, this identifies a novel function for Efemp1 in the retina.1. Roybal, C.N., et al., Aberrant accumulation of fibulin-3 in the endoplasmic reticulum leads to activation of the unfolded protein response and VEGF expression. Investigative ophthalmology & visual science, 2005. 46(11): p. 3973-9.2. Thompson, S., et al., Selective Disruption of Non-Visual Responses to Light in a Mouse Model of Malattia Leventinese. Invest. Ophthalmol. Vis. Sci., 2009. 50(5): p. 2561.
This PDF is available to Subscribers Only