Fig. 1: Neuronal degeneration is associated with mitochondrial hyperfusion in the human diabetic retina.

a, b Mitochondrial fusion was evaluated at the outer nuclear layer (ONL) of nondiabetic (ND) and diabetic (D) human donors using Cox4 immunostaining. Arrowheads indicate hyperfused mitochondrial networks. b Morphometric quantification of mitochondrial fusion (interconnectivity, average mitochondrial length and aspect ratio). Retinal micrographs from nondiabetic and diabetic human donors processed for c DAPI and d medium-wavelength opsin (M-opsin). Atrophy of cone photoreceptor outer/inner segments (arrowheads) and of synaptic terminals (arrows). e The density of DAPI⁺ nuclei at the ONL. Retinal micrographs from nondiabetic and diabetic human donors immunostained for f synaptophysin and g Calbindin. Arrowheads indicate loss of f presynaptic and g postsynaptic elements at the outer plexiform layer (OPL). h The density of synaptophysin⁺ processes at the OPL. Correlation of mitochondrial fusion (interconnectivity index) against the density of i DAPI⁺ nuclei at the ONL or j synaptophysin⁺ processes at the OPL. Regression line, significance levels (P), coefficient of determination (r²) and 95% confidence bands of the best fit line (grey) are shown. ND (n = 3 donor eyes), D (n = 7 donor eyes (b–e), n = 8 donor eyes (h)). (b–e, h) Data are presented in box-and-whisker plots with single data points (for definition of boxplot elements see “Methods” section). P values were calculated using 2-sided unpaired Student’s t-test. IS, photoreceptor inner segments; INL, inner nuclear layer; IPL, inner plexiform layer; Scale bars: 40 µm.