TY - JOUR
T1 - EML1 is essential for retinal photoreceptor migration and survival
AU - Poria, Deepak
AU - Sun, Chi
AU - Santeford, Andrea
AU - Kielar, Michel
AU - Apte, Rajendra S.
AU - Kisselev, Oleg G.
AU - Chen, Shimming
AU - Kefalov, Vladimir J.
N1 - Funding Information:
The authors wish to thank Mingyan Yang of Chen Lab, and Guangyi Ling of WU-DOVS Morphological Core for technical assistance. This work is supported by NIH grants EY027387 and EY030912 (to VK), EY012543 (to SC), EY019287 (RSA), EY028914 (to OGK) and EY002687 (to Washington University School of Medicine, Saint Louis), Jeffery T. Fort Innovation Fund (RSA), and the Starr Foundation (RSA). We acknowledge unrestricted grants from Research to Prevent Blindness to the Department of Ophthalmology and Visual Sciences at Washington University School of Medicine, Saint Louis, and to the Gavin Herbert Eye Institute at the University of California, Irvine.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Calcium regulates the response sensitivity, kinetics and adaptation in photoreceptors. In striped bass cones, this calcium feedback includes direct modulation of the transduction cyclic nucleotide-gated (CNG) channels by the calcium-binding protein CNG-modulin. However, the possible role of EML1, the mammalian homolog of CNG-modulin, in modulating phototransduction in mammalian photoreceptors has not been examined. Here, we used mice expressing mutant Eml1 to investigate its role in the development and function of mouse photoreceptors using immunostaining, in-vivo and ex-vivo retinal recordings, and single-cell suction recordings. We found that the mutation of Eml1 causes significant changes in the mouse retinal structure characterized by mislocalization of rods and cones in the inner retina. Consistent with the fraction of mislocalized photoreceptors, rod and cone-driven retina responses were reduced in the mutants. However, the Eml1 mutation had no effect on the dark-adapted responses of rods in the outer nuclear layer. Notably, we observed no changes in the cone sensitivity in the Eml1 mutant animals, either in darkness or during light adaptation, ruling out a role for EML1 in modulating cone CNG channels. Together, our results suggest that EML1 plays an important role in retina development but does not modulate phototransduction in mammalian rods and cones.
AB - Calcium regulates the response sensitivity, kinetics and adaptation in photoreceptors. In striped bass cones, this calcium feedback includes direct modulation of the transduction cyclic nucleotide-gated (CNG) channels by the calcium-binding protein CNG-modulin. However, the possible role of EML1, the mammalian homolog of CNG-modulin, in modulating phototransduction in mammalian photoreceptors has not been examined. Here, we used mice expressing mutant Eml1 to investigate its role in the development and function of mouse photoreceptors using immunostaining, in-vivo and ex-vivo retinal recordings, and single-cell suction recordings. We found that the mutation of Eml1 causes significant changes in the mouse retinal structure characterized by mislocalization of rods and cones in the inner retina. Consistent with the fraction of mislocalized photoreceptors, rod and cone-driven retina responses were reduced in the mutants. However, the Eml1 mutation had no effect on the dark-adapted responses of rods in the outer nuclear layer. Notably, we observed no changes in the cone sensitivity in the Eml1 mutant animals, either in darkness or during light adaptation, ruling out a role for EML1 in modulating cone CNG channels. Together, our results suggest that EML1 plays an important role in retina development but does not modulate phototransduction in mammalian rods and cones.
UR - http://www.scopus.com/inward/record.url?scp=85125156229&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-06571-3
DO - 10.1038/s41598-022-06571-3
M3 - Article
C2 - 35190581
AN - SCOPUS:85125156229
SN - 2045-2322
VL - 12
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 2897
ER -