Abstract
Purpose :
Light responses generated within intrinsically photosensitive retinal ganglion cells (ipRGCs) serve as the body’s biochemical synchronizer, entraining modulators to a 24hr day night cycle and are important in health maintenance. Much of what we know of ipRGC diversity and function has been learned from rodents; nocturnal animals that spend most daylight hours in dark burrows or underground. Far less is known about the diversity and function of primate ipRGCs.
Methods :
Using multi-electrode array, we record RGC light responses in dark-adapted non-human primate (NHP) retina using simple and complex visual stimuli spanning multiple illumination levels. We then pharmacologically isolate RGCs allowing identification and characterization of their intrinsic photoresponses. Waveforms are sorted across hundreds of cells within the same retina. Intrinsic (melanopsin-based) and rod & cone-derived light responses are then used to cluster ipRGCs into functional subtypes, characterizing their capacity for light encoding to a diverse range of visual stimuli.
Results :
Using unbiased clustering of primate ipRGC responses, we identify two functionally distinct subtypes (type-1 n=70 cells and type-2 n=257 cells, N=3 NHPs) with differences in intrinsic photosensitivity, time to response, and response durations, similar to M1 & M2 ipRGCs in rodents. Type-1 ipRGCs respond to luminance across the entire visual sensitivity range but have a low maximal firing rate (10-20Hz), limiting the ability of individual ipRGCs to encode differences in illumination. Type-2 ipRGCs instead, have strong rod & cone input, a large maximal firing rate (~100Hz), and incorporate melanopsin responses to encode subtle differences in contrast at photopic levels. NHP ipRGCs have less intrinsic photosensitivity (5-10x), requiring brighter light to achieve photoresponses compared to mouse. However, once activated, primate ipRGCs have prolonged response durations (>2x), providing more sustained signaling even under brief light exposure.
Conclusions :
Primates have two functional subtypes of ipRGCs, encode unique components of the visual environment and differ in their sensitivity and response duration compared to that of rodents. These findings have important health implications for humans and should be considered when designing environments with extended artificial lighting conditions such as hospitals.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.