MINI REVIEW article

Front. Neurosci., 05 August 2025

Sec. Visual Neuroscience

Volume 19 - 2025 | https://doi.org/10.3389/fnins.2025.1635101

Intrinsically photosensitive retinal ganglion cells and visual processing: ipRGCs beyond non-image-forming functions

  • Department of Psychology, New York University, New York, NY, United States

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are relatively newly discovered photoreceptors other than rods and cones. For the last decade, people have been considered ipRGCs to be primarily in charge of non-image-forming and cognitive functions. However, an increasing body of evidence has pointed out that ipRGCs also play a role in visual processing, such as contrast, brightness and color perception. In this mini-review, I listed what the caveats about those studies discussing how ipRGCs affect cognitive functions and how ipRGCs serve as image-forming functions under well-controlled condition.

Introduction

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are relatively newly discovered photoreceptors other than rods and cones. They are characterized by the photopigment—melanopsin, which makes them sensitive to light wavelength around 480 nm (; ; Pickard and Sollars, 2011; Provencio et al., 1998; Provencio et al., 2000). Over the last decade, abundant of studies have proposed how ipRGCs serve as a “non-image-forming” photoreceptor and do not involve in visual functions (see ; Meng et al., 2025 for review). However, recently, increasing evidence obtained under better controlled light conditions suggests that ipRGCs contribute to human visual perception as well.

Blue light, which ipRGCs are most sensitive to, has been indicated to delay circadian rhythm (; ; Vandewalle et al., 2006), increase alertness (; Phipps-Nelson et al., 2009; Souman et al., 2018), improve working memory (Suzuki et al., 2025; Vandewalle et al., 2013; Vandewalle et al., 2007; Vandewalle et al., 2009), improve task switching ability (; but see showing no impacts), enhance creativity (), expand time perception (Yang et al., 2018) and other cognitive functions (see ; Meng et al., 2025 for review). However, effects from blue light do not necessarily indicate that they originate from ipRGCs, especially when studies examining cognitive functions did not properly control luminance, background colors, and cone activation levels (; ; Yang et al., 2023). Specifically, most studies used different background light types (e.g., green or orange light, ; ) while failing to control luminance and the stimulation levels of cones and ipRGCs (Yang et al., 2023). This can possibly be a reason for mixed findings in several studies. A better way to control luminance would be using flicker photometry so that when the target color (i.e., blue) and the control color (e.g., green or orange) alternate at a frequency of around 10–20 Hz, the parvocellular pathway (P-pathway), which is primarily responsible for colors and sustained spatial response, will be suppressed (silenced). In the meantime, the magnocellular pathway (M-pathway) is in charge of the luminance and brightness for the two light sources, minimizing the perception of flicker and leads to identical luminance of the target and control colors (; ).

The techniques for controlling the background lights have significantly improved recently: By using silent substitution to create a metamer of the control light and stimulating ipRGCs with high versus low energy levels, researchers were able to dissociate the effects of cones and ipRGCs by using four-primary (e.g., ; ; ; Tsujimura et al., 2010; Woelders et al., 2023; Yamakawa et al., 2019; Yang et al., 2023; Yang et al., 2018; Zele et al., 2018a) or five-primary lights (e.g., ; Uprety et al., 2022; Zele et al., 2018b), depending on the luminance level and if rods have saturated at the photopic level. Indeed, compared to studies examining the effects of ipRGCs on cognitive functions which have several caveats, studies examining the effects of ipRGCs on animal vision (e.g., ; ; ; Patterson et al., 2020; Schmidt et al., 2011; Shi et al., 2025) and low-level human vision (e.g., ; Spitschan et al., 2017; Uprety et al., 2022) are under better controlled conditions.

ipRGCs contribute to color vision. More evidence has pointed out that ipRGCs are involved in color threshold () and color processing (Zele et al., 2018b), (see ) for review but Woelders et al. (2023) showing no effects of ipRGCs on color processing. If ipRGCs are changing human color vision, this could change how the trichromatic theory of color vision – the fundamental theory describing how three types of cones in the human retina can modulate the perception of a full range of colors – is mathematically computed, and the color matching functions should take this into account when examining the relations between cones and the spectral power distribution (SPD). Indeed, an experiment has revealed that traditional trichotomy can only explain perceptual sensitivity at the fovea but not in the periphery, because ipRGCs are primarily distributed in the periphery, thereby modulating the visibility there which was not account by the traditional trichotomy (). Future studies should carefully examine trichromatic theory of color vision at different eccentricities while taking ipRGCs’ distribution into consideration.

In addition to color vision, ipRGCs also contribute to contrast (; Schmidt et al., 2014; Zele et al., 2019) and brightness perception (; ; ; ; ; ; Yamakawa et al., 2019; Zele et al., 2018b), but see Vincent et al. (2021) showing that ipRGCs do not impact luminance detection. For example, two blind patients without outer retina could report brightness percept and had pupillary light response when given short-wavelength light stimuli (Zaidi et al., 2007), indicating that rods and cones are not the only determining factors mediating visual processing. Indeed, Nugent and Zele (2024) have shown that ipRGCs alone can produce visual percept in response to both spatial and temporal patterns. Additionally, by using silent substitution, have shown that increased ipRGCs stimulation led to a higher contrast sensitivity at low spatial frequencies, and this effect varied across eccentricities according to the distribution of ipRGCs on the retina. Animal models also provided supporting evidence to this finding given that mice lacking melanopsin showed deficits in contrast sensitivity (Schmidt et al., 2014). Recently, Shi et al. (2025) also demonstrated that ipRGC activation can enhance the orientation selectivity in the primary visual cortex of mice by increasing preferred-orientation responses and narrowing tuning bandwidth.

Why do ipRGCs play a role in contrast, brightness, and color perception? The visual pathways mediated by ipRGCs are still perplexed (). Despite this, mice lacking rods and cones could still do the light detection task through melanopsin (). Animal models have shown that ipRGCs project extensively to the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN), both of which play significant roles in visual perception rather than solely mediating non-image-forming functions (; ).

For human, superior colliculus can process light information bypassing the cortical pathways and plays a critical role in controlling human eye movements (; ; Manger, 2020). Interestingly, in human studies, melanopsin can stimulate the human homolog of frontal eye fields (), which also engage in eye movements planning (; Paus, 1996; Rivaud et al., 1994) and endogenous attention (). The neuroimaging evidence pointed out that ipRGCs are sending signals to neural substrates which are directly or indirectly connected to visual processing (). More neuroimaging and modeling work with good quality of control are needed to verify ipRGCs’ mechanisms between brain structures and how they are shaping human low-level vision.

Contrary to previous arguments that ipRGCs are primarily in charge of non-image-forming functions (e.g., ; Meng et al., 2025), I argued that a variety of studies examining the effects of ipRGCs on cognition have serious caveats in controlling the light conditions. For example, due to the sluggishness and the receptive field properties of ipRGCs (Procyk et al., 2015), when examining their effects on cognition, researchers should carefully control the background lights (), stimuli location (), environmental lights (Webster et al., 2007) and the adaptation time needed to stimulate ipRGCs (Procyk et al., 2015; Yang et al., 2023). In vision studies, these factors are usually well-controlled, and ipRGCs undoubtfully play a role in human visual processing, such as contrast, brightness, and color processing (; ; ). It is unknown, however, whether and how much are people metacognitively aware of the effects of ipRGCs on their cognition and perception (). Future studies could also consider how ipRGCs affect mid-level visual tasks, such as crowding, texture segregation, object localization, given the closely relationship between low- and mid-level visual processing in humans (; ; ). Additionally, understanding how animal models’ findings can be applied to humans could further clarify the evolutionary conservation of visual and non-visual pathways, revealing their functional relevance in human physiology and behaviors (; ; Tünçok et al., 2025). Most importantly, whether and how the image-forming and non-image-forming functions of ipRGCs interact could further unveil how human visual and cognitive functions integrated to support our daily lives.

Statements

Author contributions

H-HL: Project administration, Conceptualization, Writing – review and editing, Investigation, Writing – original draft.

Funding

The author(s) declare that no financial support was received for the research and/or publication of this article.

Acknowledgments

I thank Pei-Ling Yang for helpful feedback and comments on the manuscript.

Conflict of interest

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author declares that no Generative AI was used in the creation of this manuscript.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Summary

Keywords

intrinsically photosensitive retinal ganglion cells (ipRGCs), blue light, visual processing, non-image-forming functions, melanopsin

Citation

Lee H-H (2025) Intrinsically photosensitive retinal ganglion cells and visual processing: ipRGCs beyond non-image-forming functions. Front. Neurosci. 19:1635101. doi: 10.3389/fnins.2025.1635101

Received

26 May 2025

Accepted

15 July 2025

Published

05 August 2025

Volume

19 - 2025

Edited by

Mario Senden, Maastricht University, Netherlands

Reviewed by

Birke Benedikter, Philipps-Universität Marburg, Germany

Updates

Copyright

© 2025 Lee.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Hsing-Hao Lee,

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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