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Functional diversity of human intrinsically photosensitive retinal ganglion cells

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Science  06 Dec 2019:
Vol. 366, Issue 6470, pp. 1251-1255
DOI: 10.1126/science.aaz0898
  • Fig. 1 A subset of human RGCs is intrinsically photosensitive.

    (A) Representative individual ipRGC spike trains to a 30-s light pulse (~1013 photons/cm2 per second, 470 nm) from five different human donors. (B) Average ipRGCs’ response latency, duration, and amplitude in each donor (n = 7, 15, 4, and 15 for donors 1, 2, 3, and 5, respectively, where n is the number of cells). Representative individual ipRGCs spike trains (C) and average responses (D) to three identical 30-s light pulses (~1013 photons/cm2 per second, 470 nm) from a control recording [n = 3; upper panel in (C), white histogram in (D)] or a recording with opsinamide (n = 9; lower panel in (C), red histogram in (D)] during the second stimulation [***P < 0.001, **P < 0.01, ANOVA (analysis of variance), Bonferroni post hoc test, one donor]. (E) Responses of ipRGCs stimulated for 30 s at different irradiances (from 2 × 1011 to 2 × 1014 photons/cm2per second, 470 nm) in each donor (n = 7, 14, 4, and 15 for donors 1, 2, 3, and 5, respectively). ph, photons. Blue bars and blue background in (A) and (C) indicate light pulses.

  • Fig. 2 Human ipRGCs display different subtypes.

    (A) Representative responses from type 1, 2, and 3 ipRGCs to increasing irradiance light pulses [30 s, 470 nm, irradiances (irr) 1, 2, 3, and 4: 2.9 × 1011, 3.5 × 1012, 2 × 1013, and 2 × 1014 photons/cm2 per second, respectively]. Blue bars indicate light pulses. (B) Corresponding dose–response curves (type 1, n = 24, four donors; type 2, n = 18, four donors; type 3, n = 79, one donor). Error bars indicate SEM. (C) Representative raster plots of type 1 and 2 ipRGCs and average traces in response to 10-min light stimulations (~2 × 1013 photons/cm2 per second, 470 nm; type 1, n = 5, and type 2, n = 3). (D) Principal components of the ipRGCs’ response parameters (sensitivity, latency, and duration; n = 121, four donors).

  • Fig. 3 Spectral sensitivity of human ipRGCs.

    (A) Dose–response curves of each subtype to 30-s light pulses at different irradiances and wavelengths (irr1 to irr4, from 5 × 1010 to 5 × 1014 photons/cm2 per second; 447, 470, 505, 530, and 560 nm) (type 1, n = 7; type 2, n = 8; type 3, n = 79; one donor). Error bars indicate SEM. (B) Action spectra and (C) best-fitted nomograms for each subtype. EC, irradiance required to drive a 50% response; λ, wavelength.

  • Fig. 4 Human ipRGCs integrate extrinsic signals.

    (A) Individual examples of conventional RGCs’ and type 1, 2, and 3 ipRGCs’ responses to increasing irradiance light pulses before (black traces) and after (color traces) application of synaptic blockers (30 s, 470 nm; irr1, irr2, irr3, and irr4: 2.9 × 1011, 3.5 × 1012, 2 × 1013, and 2 × 1014 photons/cm2 per second, respectively). Response properties before (black bars and symbols) and after (colored bars and symbols) application of synaptic blockers are shown in (B) and (C). (B) Threshold and latency (effect of irradiance: type 1, P < 0.05; type 2, P < 0.001; type 3, P < 0.001; effect of drugs: type 1, P < 0.01; type 2, P < 0.01; type 3, P < 0.001; two-way ANOVAs, Bonferroni post hoc tests). (C) Average ipRGCs’ sensitivity. In both (B) and (C): type 1, n = 9; type 2, n = 9; and type 3, n = 78. Error bars in (C) indicate SEM.

Supplementary Materials

  • Functional diversity of human intrinsically photosensitive retinal ganglion cells

    Ludovic S. Mure, Frans Vinberg, Anne Hanneken, Satchidananda Panda

    Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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    • Materials and Methods 
    • Figs. S1 to S6
    • Tables S1 to S3
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