Intrinsically Photosensitive Retinal Ganglion Cells of the Human Retina

Abstract

Light profoundly affects our mental and physical health. In particular, light, when not delivered at the appropriate time, may have detrimental effects. In mammals, light is perceived not only by rods and cones but also by a subset of retinal ganglion cells that express the photopigment melanopsin that renders them intrinsically photosensitive (ipRGCs). ipRGCs participate in contrast detection and play critical roles in non-image-forming vision, a set of light responses that include circadian entrainment, pupillary light reflex (PLR), and the modulation of sleep/alertness, and mood. ipRGCs are also found in the human retina, and their response to light has been characterized indirectly through the suppression of nocturnal melatonin and PLR. However, until recently, human ipRGCs had rarely been investigated directly. This gap is progressively being filled as, over the last years, an increasing number of studies provided descriptions of their morphology, responses to light, and gene expression. Here, I review the progress in our knowledge of human ipRGCs, in particular, the different morphological and functional subtypes described so far and how they match the murine subtypes. I also highlight questions that remain to be addressed. Investigating ipRGCs is critical as these few cells play a major role in our well-being. Additionally, as ipRGCs display increased vulnerability or resilience to certain disorders compared to conventional RGCs, a deeper knowledge of their function could help identify therapeutic approaches or develop diagnostic tools. Overall, a better understanding of how light is perceived by the human eye will help deliver precise light usage recommendations and implement light-based therapeutic interventions to improve cognitive performance, mood, and life quality.

In vivo optogenetic stimulation of the primate retina activates the visual cortex after long-term transduction

“…In this way, we were able to compare VEP responses before and after the intravitreal injection of synaptic blockers (2,3-piperidine dicarboxylic acid [PDA] and L-(+)-2-amino-4-phosphonobutyric acid [L-AP4]) into both eyes ( Figure 3 B) to block natural retinal responses to light. 34 The kinetic of action for the two blockers was first determined by a control electro-retinogram (ERG) experiment on a naive animal ( Figure S3 ) that showed a complete suppression of the ERG's b-wave in 40 min that lasted 24 h. With the synaptic block, light stimulation directly activates the engineered cells rather than the normal retinal pathway. In monkey M1, before the injection of the blocker, both VEP responses (black curves) were similar after stimulation of the ChR-tdT-expressing eye with an orange LED (595 nm, ChR-tdT eye, left panel) and for stimulation of the control eye (right panel), confirming that the sequence of orange flashes in both eyes activated the visual pathway naturally.…”

Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy

“…Given the fact that melanopsin-driven light responses originating from intrinsically photosensitive retinal ganglion cells (ipRGCs) seem to be upregulated in degenerated mouse retina [ 57 ], we focused solely on light responses that peaked early on (during the light flash), which is uncharacteristic for melanopsin [ 58 ]. Moreover, the presence of such responses hints toward the preservation of a functional inner retinal network, given the nature of the mGluR6 signalling [ 36 , 37 ].…”

PupilEXT: Flexible Open-Source Platform for High-Resolution Pupillometry in Vision Research

“…The discovery of a new type of receptors in the outer retina called intrinsically photosensitive retinal ganglion cells (ipRGCs) was a turning point of vision science (Provencio et al, 1998(Provencio et al, , 2000Gooley et al, 2001;Berson et al, 2002;Hattar, 2002;Mure, 2021), which has led to a rethinking of classical retinal processing models. This subset of ganglion cells are part of the non-image-forming mechanism of the eye because of their projection to regions of the suprachiasmatic nucleus (SCN) and olivary pretectal nucleus (OPN) (Ruby et al, 2002;Berson, 2003;Hattar et al, 2003;Do et al, 2009;Ecker et al, 2010;Allen et al, 2019;Do, 2019).…”