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Retinal light perception and biological rhythms: The role of light in sleep and mood from an ophthalmic perspective (Review)

  • Authors:
    • Man Yuan
    • Hanxiang Liu
    • Ranjie Zhu
    • Yuzhen Li
    • Siyuan Song
    • Anhuai Yang
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, School of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China, Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA, Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
    Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 16
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    Published online on: October 29, 2025
       https://doi.org/10.3892/mmr.2025.13726
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Abstract

Light is the paramount environmental signal for the entrainment of endogenous circadian rhythms. Its non‑visual effects, mediated by the retina, exert a profound control over human sleep, mood and systemic physiological homeostasis. Beyond its canonical function in image formation, the retina operates as a primary irradiance detector through a specialized class of neurons, the intrinsically photosensitive retinal ganglion cells (ipRGCs), which utilize the photopigment melanopsin. These cells convey environmental light information directly to the suprachiasmatic nucleus (SCN), the brain's master circadian pacemaker, thereby synchronizing the body's internal timekeeping with the external solar cycle. Compelling evidence demonstrates that the spectral quality of light, particularly within the short‑wavelength blue range, potently modulates neuroendocrine and neural systems via the ipRGC pathway, governing melatonin synthesis, the architecture of the sleep‑wake cycle and affective regulation. The modern light environment, characterized by ubiquitous artificial light at night and pathological states of light perception resulting from ophthalmic diseases such as glaucoma and retinal degenerations, can severely disrupt this synchronization. The consequent circadian misalignment is a significant etiological factor in sleep disorders, depressive symptoms and other systemic morbidities. The retina's integral position within the light‑rhythm‑behavior axis is thus a critical nexus between the visual system and systemic physiology. In addition, the present study outlined the nitric oxide‑cyclic GMP signaling axis in SCN as a critical mediator of photic entrainment. This review provided an in‑depth analysis from an ophthalmic perspective, synthesizing evidence from animal models and human studies to dissect the complex molecular, cellular and network‑level mechanisms of retinal circadian regulation, explore how aberrant photic signaling impacts sleep and mood and critically evaluate the potential of targeted interventions such as light therapy and spectral management in the context of rhythm‑related disorders.
View Figures

Figure 1

Retinal input and intracellular
signaling underlying photic entrainment of the SCN. Light is
detected by melanopsin-expressing ipRGCs in the retina and conveyed
to the SCN via the RHT, which releases glutamate and PACAP. In SCN
neurons, glutamate activates NMDA receptors, elevating
Ca2+ and engaging CaMKII/ERK, which promotes CREB
(Ser133) phosphorylation and PER1/PER2 expression. In parallel,
Ca2+ activates nNOS and NO stimulates sGC to increase
cGMP, activating PKG that further supports CREB phosphorylation and
clock-gene induction. PACAP acting on PAC1 receptors modulates
these processes and stabilizes entrainment. SCN, suprachiasmatic
nucleus; ipRGCs, intrinsically photosensitive retinal ganglion
cells; RHT, retinohypothalamic tract; PACAP, pituitary adenylate
cyclase-activating polypeptide; NMDA, N-methyl-D-aspartate; CaMKII,
calmodulin-dependent protein kinase II; CREB, cAMP response
element-binding protein; period circadian protein homolog; nNOS,
neuronal nitric oxide synthase; NO, nitric oxide; sGC, soluble
guanylyl cyclase; cGMP, cyclic guanosine monophosphate; PKG,
protein kinase G; AVP, arginine vasopressin; VIP, vasoactive
intestinal polypeptide.

Figure 2

Interaction between retinal light
perception, the retinal circadian clock and the central clock.
Light is detected by ipRGCs and retinal circuits, triggering
rhythmic dopamine release that modulates retinal sensitivity via
gap junctions. ipRGCs convey light information to the SCN to
synchronize central rhythms. In return, SCN signals regulate the
autonomous retinal clock, which controls local gene expression and
physiology in a 24-h cycle. This bidirectional system ensures
coordinated circadian regulation within the retina and the whole
organism. SCN, suprachiasmatic nucleus; ipRGCs, intrinsically
photosensitive retinal ganglion cells; pCREB, phosphorylated cAMP
response element-binding protein.

Figure 3

Retinal light input coordinates
circadian rhythms and systemic health. Retinal light signals via
the retinohypothalamic tract entrain the central circadian clock
(SCN) to synchronize peripheral clocks and systemic physiology.
Disrupted retinal signaling from disease or abnormal light causes
circadian misalignment, affecting metabolism, cell cycle and
immunity, contributing to chronic diseases. Direct retinal
projections to non-circadian brain areas link light perception with
mood and mental health. SCN, suprachiasmatic nucleus; ipRGCs,
intrinsically photosensitive retinal ganglion cells; pCREB,
phosphorylated cAMP response element-binding protein; BDNF,
brain-derived neurotrophic factor; NREM, non-rapid eye
movement.
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Copy and paste a formatted citation
Spandidos Publications style
Yuan M, Liu H, Zhu R, Li Y, Song S and Yang A: Retinal light perception and biological rhythms: The role of light in sleep and mood from an ophthalmic perspective (Review). Mol Med Rep 33: 16, 2026.
APA
Yuan, M., Liu, H., Zhu, R., Li, Y., Song, S., & Yang, A. (2026). Retinal light perception and biological rhythms: The role of light in sleep and mood from an ophthalmic perspective (Review). Molecular Medicine Reports, 33, 16. https://doi.org/10.3892/mmr.2025.13726
MLA
Yuan, M., Liu, H., Zhu, R., Li, Y., Song, S., Yang, A."Retinal light perception and biological rhythms: The role of light in sleep and mood from an ophthalmic perspective (Review)". Molecular Medicine Reports 33.1 (2026): 16.
Chicago
Yuan, M., Liu, H., Zhu, R., Li, Y., Song, S., Yang, A."Retinal light perception and biological rhythms: The role of light in sleep and mood from an ophthalmic perspective (Review)". Molecular Medicine Reports 33, no. 1 (2026): 16. https://doi.org/10.3892/mmr.2025.13726
Copy and paste a formatted citation
x
Spandidos Publications style
Yuan M, Liu H, Zhu R, Li Y, Song S and Yang A: Retinal light perception and biological rhythms: The role of light in sleep and mood from an ophthalmic perspective (Review). Mol Med Rep 33: 16, 2026.
APA
Yuan, M., Liu, H., Zhu, R., Li, Y., Song, S., & Yang, A. (2026). Retinal light perception and biological rhythms: The role of light in sleep and mood from an ophthalmic perspective (Review). Molecular Medicine Reports, 33, 16. https://doi.org/10.3892/mmr.2025.13726
MLA
Yuan, M., Liu, H., Zhu, R., Li, Y., Song, S., Yang, A."Retinal light perception and biological rhythms: The role of light in sleep and mood from an ophthalmic perspective (Review)". Molecular Medicine Reports 33.1 (2026): 16.
Chicago
Yuan, M., Liu, H., Zhu, R., Li, Y., Song, S., Yang, A."Retinal light perception and biological rhythms: The role of light in sleep and mood from an ophthalmic perspective (Review)". Molecular Medicine Reports 33, no. 1 (2026): 16. https://doi.org/10.3892/mmr.2025.13726
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