Michelle L. Maynard

Rod and cone pathway signaling and interaction under mesopic illumination.

This study investigates the time-course and post-receptoral pathway signaling of photoreceptor interactions when the rod (R) and three cone (L, M, S) photoreceptor classes contribute to mesopic vision. A four-primary photostimulator independently controls photoreceptor activity in human observers. The first experiment defines the temporal adaptation response of receptoral (L-, S-cone, rod) and post-receptoral (LMS, LMSR, +L-M) signaling and interactions. Here we show that nonopponent cone-cone interactions (L-cone, LMS, LMSR) have monophasic temporal response patterns whereas opponent signals (+L-M, S-cone) show biphasic response patterns with slower recovery. By comparison, rod-cone interactions with nonopponent signals have faster adaptation responses and reduced sensitivity loss whereas opponent rod-cone interactions are small or absent. Additionally, the rod-rod interaction differs from these interaction types and acts to increase rod sensitivity due to temporal summation but with a slower time course. The second experiment shows that the temporal profile of the rod signal alters the relative rod contributions to the three primary post-receptoral pathways. We demonstrate that rod signals generate luminance (+L+M) signals mediated via the MC pathway with all rod temporal profiles and chromatic signals (L/L+M, S/L+M) in both the PC and KC pathways with durations >75 ms. Thus, we propose that the change in relative weighting of rod signals within the post-receptoral pathways contributes to the sensitivity and temporal response of rod and cone pathway signaling and interactions.

Melanopsin-Mediated Post-Illumination Pupil Response in Early Age-Related Macular Degeneration.

PURPOSE To determine whether melanopsin-expressing intrinsically photosensitive retinal ganglion cell (ipRGC) inputs to the pupil light reflex (PLR) are affected in early age-related macular degeneration (AMD). METHODS The PLR was measured in 40 participants (20 early AMD and 20 age-matched controls) using a custom-built Maxwellian view pupillometer. Sinusoidal stimuli (0.5 Hz, 11.9 seconds duration, 35.6° diameter) were presented to the study eye and the consensual pupil response was measured to lights with high melanopsin excitation (464 nm [blue]) and with low melanopsin excitation (638 nm [red]) that biased activation to the outer retina. Two melanopsin PLR metrics were quantified: the phase amplitude percentage (PAP) during the sinusoidal stimulus presentation and the post-illumination pupil response (PIPR). The PLR during stimulus presentation was analyzed using latency to constriction, the transient pupil response and maximum pupil constriction metrics. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves. RESULTS The blue PIPR was significantly less sustained in the early AMD group (P < 0.001). The red PIPR was not significantly different between groups (P > 0.05). The PAP and blue stimulus constriction amplitude were significantly lower in the early AMD group (P < 0.05). There was no significant difference between groups in the latency or transient amplitude for both stimuli (P > 0.05). ROC analysis showed excellent diagnostic accuracy for the blue PIPR metrics (area under the curve > 0.9). CONCLUSIONS This is the initial report that the melanopsin-controlled PIPR is dysfunctional in early AMD. The noninvasive, objective measurement of the ipRGC controlled PIPR has excellent diagnostic accuracy for early AMD.

Intrinsically photosensitive retinal ganglion cell function, sleep efficiency and depression in advanced age-related macular degeneration

Purpose Melanopsin expressing intrinsically photosensitive retinal ganglion cells (ipRGC) input to multiple brain regions including those for pupil control, circadian rhythms, sleep and mood regulation. Here we measured ipRGC function and its relationship to sleep quality and depression in patients with advanced AMD. Methods The melanopsin-mediated post-illumination pupil response (PIPR) was measured in 53 patients with advanced AMD (age 78.8 ± 8.8 years) and in 20 healthy controls (age 72.5 ± 3.3 years). Sleep quality and efficiency was assessed using the Pittsburgh Sleep Quality Index (PSQI). Risk of depression was determined using the Center for Epidemiologic Studies Depression questionnaire. Results The group with AMD showed significantly reduced pupil constrictions (P = 0.039); PIPR amplitudes (P = 0.003); global sleep scores (P = 0.01); and higher levels of depression (P < 0.001) than the control group. There was a significant correlation between the PIPR amplitude and global sleep score in the AMD group (P = 0.01). The amplitude of PIPR significantly correlated with sleep efficiency (P = 0.008; regression, P = 0.01, R2 = 0.13), but not sleep quality (P = 0.23) in the AMD group. There was no correlation between PIPR and depression scores. Conclusions Intrinsically photosensitive RGC dysfunction in advanced AMD contributes to the observed reduction in sleep efficiency. The correlation between the melanopsin-mediated PIPR and sleep may indicate reduced photic input to the suprachiasmatic nucleus and ventrolateral preoptic area due to ipRGC dysfunction in AMD.

Melanopsin photoreception contributes to human visual detection, temporal and colour processing

The visual consequences of melanopsin photoreception in humans are not well understood. Here we studied melanopsin photoreception using a technique of photoreceptor silent substitution with five calibrated spectral lights after minimising the effects of individual differences in optical pre-receptoral filtering and desensitising penumbral cones in the shadow of retinal blood vessels. We demonstrate that putative melanopsin-mediated image-forming vision corresponds to an opponent S-OFF L + M-ON response property, with an average temporal resolution up to approximately 5 Hz, and >10x higher thresholds than red-green colour vision. With a capacity for signalling colour and integrating slowly changing lights, melanopsin-expressing intrinsically photosensitive retinal ganglion cells maybe the fifth photoreceptor type for peripheral vision.

Effect of rod–cone interactions on mesopic visual performance mediated by chromatic and luminance pathways

We studied the effect of rod-cone interactions on mesopic visual reaction time (RT). Rod and cone photoreceptor excitations were independently controlled using a four-primary photostimulator. It was observed that (1) lateral rod-cone interactions increase the cone-mediated RTs; (2) the rod-cone interactions are strongest when rod sensitivity is maximal in a dark surround, but weaker with increased rod activity in a light surround; and (3) the presence of a dark surround nonselectively increased the mean and variability of chromatic (+L-M, S-cone) and luminance (L+M+S) RTs independent of the level of rod activity. The results demonstrate that lateral rod-cone interactions must be considered when deriving mesopic luminous efficiency using RT.

Mesopic Pelli–Robson contrast sensitivity and MP‐1 microperimetry in healthy ageing and age‐related macular degeneration

To determine whether decreasing illumination of the Pelli‐Robson contrast sensitivity (CS) chart and MP‐1 microperimeter to low mesopic conditions is more sensitive to vision changes occurring with healthy ageing and in early and intermediate age‐related macular degeneration (AMD) and whether these mesopic tests can differentiate visual function between healthy older participants with and without AMD risk genotypes.