Calcium dynamics change in degenerating cone photoreceptors

Cone photoreceptors (cones) are essential for high-resolution daylight vision and colour perception. Loss of cones in hereditary retinal diseases has a dramatic impact on human vision. The mechanisms underlying cone death are poorly understood, and consequently, there are no treatments available. Previous studies suggest a central role for calcium (Ca2+) homeostasis deficits in photoreceptor degeneration; however, direct evidence for this is scarce and physiological measurements of Ca2+ in degenerating mammalian cones are lacking.
Here, we took advantage of the transgenic HR2.1:TN-XL mouse line that expresses a genetically encoded Ca2+ biosensor exclusively in cones. We cross-bred this line with mouse models for primary ("cone photoreceptor function loss-1", cpfl1) and secondary ("retinal degeneration-1", rd1) cone degeneration, respectively, and assessed resting Ca2+ levels and light-evoked Ca2+ responses in cones using two-photon imaging. We found that Ca2+ dynamics were altered in cpfl1 cones, showing higher noise and variable Ca2+ levels, with significantly wider distribution than for wild-type and rd1 cones. Unexpectedly, up to 21% of cpfl1 cones still displayed light-evoked Ca2+ responses, which were larger and slower than wild-type responses. In contrast, genetically intact rd1 cones were characterized by lower noise and complete lack of visual function.
Our study demonstrates alterations in cone Ca2+ dynamics in both primary and secondary cone degeneration. Our result...

Source: Human Molecular Genetics - January 3, 2017 Category: Genetics & Stem Cells Authors: Kulkarni, M., Trifunovic, D., Schubert, T., Euler, T., Paquet-Durand, F. Tags: ARTICLES Source Type: research