Photobiomodulation Science

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How might photobiomodulation affect cells?

Red and near-infrared light · proposed starting routes, reported cell changes and later responses

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01Light exposure

Red &
near-infrared

RedNear-IR
Light enters tissue
Wavelength
nm
Irradiance
mW/cm²
Exposure time
seconds / minutes

Equal energy per area can still produce different effects when intensity or exposure time changes.1

Light delivery

Light must reach and be absorbed by a target to initiate a response.

Red and near-infrared describe spectral ranges. Either lasers or LEDs can supply these wavelengths; the label alone does not specify the exposure.2

02Proposed starting routes

Several explanations are being tested. Their roles may differ by wavelength, cell type and tissue condition.

Mitochondria and CCO

The mitochondrial explanation centered on cytochrome c oxidase (CCO) has long been the prevailing view in PBM literature, shaped by Karu’s early work and cellular action-spectrum studies.34 Studies report changes in respiration and mitochondrial membrane potential after PBM. 5 However, experiments testing CCO directly have produced conflicting results. 6

Direct evidence that red/NIR light releases inhibitory NO from CCO remains limited. In an isolated-enzyme study, 670 and 830 nm light did not relieve NO inhibition; those conditions differed from living tissue. 7 In isolated mitochondria, 442 nm blue light partly reversed NO inhibition at complex IV, whereas 650 nm red light had no reliable effect.8 Blue light, and more weakly 629 nm red light, accelerated recovery of NO-inhibited respiration in rat liver homogenates.9

NO release and formation

Light may release NO from bound stores in hemoglobin, myoglobin or S-nitrosothiols. 10 11 Promoting new NO formation from nitrite is a separate proposed route. Oxygen availability strongly affects this chemistry; evidence for NO involvement does not prove release from CCO. 12 6

Other proposed light absorbers

Reviews have also proposed flavoproteins, endogenous porphyrins and membrane-associated cytochromes as light absorbers that could alter cellular redox signaling.13 Their contribution to red/NIR PBM remains uncertain. Much of the direct flavin evidence concerns blue light, so these candidates should not be treated as established red/NIR targets.14

Ion-channel pathways

Channels can alter calcium movement in response to light-sensitive proteins, redox changes or local heating. Much of the opsin evidence concerns blue or green light and cannot automatically be extended to red/NIR exposure. 15

Water near cell structures

Changes in thin water layers near proteins could affect ATP synthase or ion channels. Reduced water-layer viscosity and water-mediated channel activation remain hypotheses. 16 17

Outside the cell: TGF-β1

ROS can activate latent transforming growth factor beta-1. The active factor binds to receptors and influences differentiation, immune responses and tissue remodeling. This route can start outside the cell, rather than inside mitochondria. 18 19

03Reported cell changes

ATP

Cellular energy supply

Levels have increased in many cell and tissue models. ATP supports biosynthesis, transport and repair. Its measured amount reflects both production and use: a higher level alone does not establish which mitochondrial step changed, and an increase is not universal. 5 2

ROS

Reactive oxygen species

A brief, small rise can activate redox-sensitive signaling and protective responses. In stressed cells, excess ROS production may instead decrease. Large or sustained amounts can damage proteins, membranes and DNA. Timing and starting cell state help explain these different findings. 20 5

NO

Nitric oxide

Can relax blood vessels and regulate respiration, but can also inhibit CCO. Effects depend on concentration, oxygen and the location of release or formation. A change in NO availability may influence nearby cells as well as the illuminated cell. 6 11

Ca²⁺

Calcium ions

Calcium can enter from outside the cell or move between the cytosol, endoplasmic reticulum and mitochondria. The size and duration of a calcium signal influence metabolism, gene activity and survival; a rise is not automatically beneficial. 2 5

↔ These changes interact

These signals interact: calcium and oxidants can alter mitochondria, which can change the signals in turn. Several routes may operate together, rather than as a fixed sequence.5

04Later responses

Metabolic adaptation

Respiration, energy use and antioxidant defenses can change. Later responses may include altered mitochondrial mass and function, helping cells adapt to metabolic stress. 5

Gene and protein activity

Signaling can activate transcription factors and change gene expression, protein production and growth-factor responses. These changes may outlast the light exposure; early signaling and later tissue outcomes are different measurements. 2

Cell behavior

Proliferation, migration, differentiation and survival may change. Moving cells can help close a wound; reduced programmed cell death can preserve injured tissue. The same response can help one tissue or injury stage while being undesirable in another context. 2 19

Immune and tissue responses

Inflammatory mediators and immune-cell activity may change, alongside blood flow, matrix remodeling and repair. PBM does not simply suppress all inflammation: direction and timing depend on the model and cell state. 15

Local and possible distant effects

Responses have been reported outside illuminated tissue, including in animal neuroprotection models. Circulating signals or cells may contribute; mediators and the extent of these effects remain uncertain. 21 22

The timing matters: rapid biochemical signals can precede slower changes in proteins, cell behavior and tissue structure.2

What these responses can look like in cells and tissues

Selected findings from cell cultures, animal injury and disease models, and human tissue. Direction and size depend on exposure and model; these examples do not establish benefits in patients.

Cell stress protection

Stronger defenses · less damage

Rat burn models report higher catalase and less lipid or protein oxidation alongside improved wound repair.24 In stressed bone-forming cells, improved protein folding accompanied reduced apoptosis.25

Cell survival and movement

Greater viability and migration

Human tendon fibroblast cultures showed increased viability, proliferation and movement into a cell-free gap.26 In rat burn wounds, increased cell-proliferation markers accompanied repair, connecting cellular responses with replenishment of injured tissue.27

Inflammatory signaling

Changes in mediators and cells

Rat burn models report lower TNF-α and IL-1β alongside improved repair.24 In injured rat muscle, vascular PBM changed early macrophage recruitment and repair-associated markers at different healing stages.28

Vascular responses

Oxygenation and vessel integrity

Human forearm studies measured more oxygenated hemoglobin and a higher oxidized CCO signal.29 In rat brain ischemia/reperfusion, PBM reduced vascular leakage and preserved vessel-lining cells.30

Tissue rebuilding

New tissue and matrix organization

Rat burn wounds showed altered collagen organization and increased repair markers.27 Rats with spinal cord injury and bone defects formed more new bone, but the measured mechanical strength did not improve alongside it.31

Mitochondrial organization

Shape, connectivity and turnover

After global cerebral ischemia in rats, PBM reduced mitochondrial fragmentation, shifted division and fusion proteins, and reduced excessive mitochondrial removal. These changes accompanied preservation of hippocampal neurons and memory, linking organelle organization with tissue function.32

Cell differentiation

Acquiring specialized functions

Human stem-cell cultures showed increased differentiation toward bone-forming cells.17 In dystrophic mice, PBM altered muscle differentiation proteins alongside reduced fiber degeneration.33 These responses link specialized cellular functions with rebuilding tissue.

Neural connections

Synapses and myelin support

An Alzheimer-like rat model showed preserved synaptic proteins and dendritic spines alongside better memory.34 In a mouse demyelination model, PBM supported myelin preservation and motor coordination, linking neuronal connections and their insulation with brain function.35

Pain-related signaling

Changes in neuronal sensitivity

In diabetic neuropathy rats, PBM reduced neuronal sensitization, p38 signaling and pain hypersensitivity. Dorsal-root ganglion inflammatory mediators and calcium responses also changed, linking cellular signaling with altered pain processing.36

Cellular senescence

Stress-related growth arrest

In ischemic endothelial cell and rat brain models, PBM reduced p21 and DNA-damage markers alongside improved vascular integrity. These findings suggest effects on stress-associated growth arrest in vessel-lining cells, connecting cellular aging with the integrity of injured tissue.30

Cellular cleanup

Protein handling and recycling

Autophagy recycles damaged cell components. In tau-related mouse models, light increased autophagy-associated proteins and HSP70 while reducing toxic tau oligomers and memory deficits.37 This suggests altered protein handling; the markers alone do not prove faster clearance.

Intercellular communication

Signals released to other cells

PBM-preconditioned stem cells secreted more vessel-growth factors; transferring them into irradiated mice preserved intestinal microvessels.38 Human keratinocytes also released more microvesicles after PBM.39 These are signals to other cells; the mouse study combined PBM with cell therapy.

Epithelial barriers

Keeping tissue boundaries intact

In a mouse colitis model, red LED treatment preserved the organization of claudin-1, a protein in epithelial tight junctions. It also reduced epithelial apoptosis, ulcers and crypt injury while increasing crypt-cell proliferation.40 These changes illustrate protection of the intestinal lining that separates tissue from the gut lumen.

Cell adhesion and shape

Attachment to the surrounding matrix

In mouse fibroblast cultures, red LED exposure increased attachment to fibronectin, but not to type I collagen, and reduced cellular shrinkage.41 This illustrates selective changes in cell–matrix interactions and cell shape, beyond movement alone. Their contribution to healing in intact tissue still needs direct testing.

Excess scarring

Limiting pathological matrix buildup

In injured rat Achilles tendons, PBM reduced excess collagen and tissue abnormalities.42 In fibroblast cultures, red light inhibited TGF-β1-driven conversion to scar-forming myofibroblasts.43 Collagen may increase during repair but decrease where excess accumulation causes scarring.

Factors that shape the response

Wavelength

In cultured human adipose-derived stem cells, blocking temperature-sensitive calcium channels suppressed responses to 980 nm but not 810 nm. Cooling during exposure also removed the 980-nm response. These experiments suggest different starting routes at the two wavelengths, rather than one mechanism for all red/NIR light.17

Intensity, duration and response time

Too little or too much exposure can weaken or reverse a response.44 In a mouse pressure-ulcer model, the same daily energy per area produced different healing responses when intensity and exposure duration changed.1 In cultured mouse muscle cells, ATP and mitochondrial membrane potential peaked 3–6 hours after exposure, rather than immediately. This illustrates a delayed cellular response; it does not establish an optimal treatment interval for people.45

Cell state and tissue type

In cultured mouse cortical neurons, 810-nm light increased ROS in unstressed cells but reduced elevated ROS after oxidative stress. Mitochondrial membrane potential increased in both conditions, and stressed cells were protected from death.46 The same exposure therefore produced different redox responses according to the cells’ starting state.

Delivery and depth

The exposure at the skin differs from that received by deeper cells. Absorption and scattering weaken and redistribute light, while beam area, wavelength and pulsing affect delivery.47 A surface dose cannot therefore be copied directly into a cell-culture experiment: the light reaching the target must also be considered.

Oxygen and injury stage

Low oxygen changes respiration and nitrite-to-NO chemistry.12 In a rat brain ischemia–reperfusion model, 750/950-nm light inhibited CCO and reduced brain injury. The authors proposed that slowing respiration during reperfusion limited excess ROS.23 This is a specific example of protection through reduced mitochondrial activity, rather than a universal need to increase it.

Metabolic conditions

In mouse fibroblast cultures with glucose, PBM increased ATP by about 35% in normal medium and reduced ROS by about 30% in nutrient-stressed medium, measured one hour after treatment. Cultures without glucose did not show these PBM effects. The differences were no longer significant at 18 hours, and cell viability and proliferation did not improve.48

Time of day and sleep

Daily rhythms. In fruit flies, 670-nm light increased ATP at 08:00 and 11:00, but not at 05:00 or 16:00.49 A small exploratory human study found improved colour-contrast sensitivity after a 3-minute morning exposure (08:00–09:00), lasting up to one week. An afternoon subgroup (12:00–13:00) showed no improvement. The study measured vision, rather than retinal ATP, and was not a randomized morning-versus-afternoon trial.50

Sleep versus wakefulness. In rats with glioma, treatment during sleep reduced tumor volume more than treatment while awake, alongside stronger brain drainage and immune responses. Survival did not differ between the two treated groups. These findings do not establish an optimal timing for humans.51

References

  1. Lanzafame RJ et al. 2007. Reciprocity of exposure time and irradiance on energy density during photoradiation on wound healing in a murine pressure ulcer model. Lasers Surg Med.
  2. de Freitas LF et al. 2016. Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy. IEEE J Sel Top Quantum Electron.
  3. Karu T. 1999. Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B.
  4. Karu TI et al. 2005. Exact action spectra for cellular responses relevant to phototherapy. Photomed Laser Surg.
  5. Hamblin MR. 2018. Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation. Photochem Photobiol.
  6. Quirk BJ et al. 2020. What Lies at the Heart of Photobiomodulation: Light, Cytochrome C Oxidase, and Nitric Oxide-Review of the Evidence. Photobiomodul Photomed Laser Surg.
  7. Quirk B et al. 2021. Effect of Red-to-Near Infrared Light and a Nitric Oxide Donor on the Oxygen Consumption of Isolated Cytochrome c Oxidase. Photobiomodul Photomed Laser Surg.
  8. Buravlev EA et al. 2015. Are the mitochondrial respiratory complexes blocked by NO the targets for the laser and LED therapy? Lasers Med Sci.
  9. Dungel P et al. 2008. Illumination with blue light reactivates respiratory activity of mitochondria inhibited by nitric oxide, but not by glycerol trinitrate. Arch Biochem Biophys.
  10. Lohr NL et al. 2009. Enhancement of nitric oxide release from nitrosyl hemoglobin and nitrosyl myoglobin by red/near infrared radiation: potential role in cardioprotection. J Mol Cell Cardiol.
  11. Keszler A et al. 2018. Wavelength-dependence of vasodilation and NO release from S-nitrosothiols and dinitrosyl iron complexes by far red/near infrared light. Arch Biochem Biophys.
  12. Ball KA et al. 2011. Low intensity light stimulates nitrite-dependent nitric oxide synthesis but not oxygen consumption by cytochrome c oxidase: Implications for phototherapy. J Photochem Photobiol B.
  13. Lubart R et al. 2005. Low-energy laser irradiation promotes cellular redox activity. Photomed Laser Surg.
  14. Serrage H et al. 2019. Under the spotlight: mechanisms of photobiomodulation concentrating on blue and green light. Photochem Photobiol Sci.
  15. Hamblin MR. 2017. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys.
  16. Sommer AP et al. 2015. Light Effect on Water Viscosity: Implication for ATP Biosynthesis. Sci Rep.
  17. Wang Y et al. 2017. Photobiomodulation of human adipose-derived stem cells using 810nm and 980nm lasers operates via different mechanisms of action. Biochim Biophys Acta Gen Subj.
  18. Arany PR et al. 2014. Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration. Sci Transl Med.
  19. Arany PR. 2022. Photobiomodulation-Activated Latent Transforming Growth Factor-β1: A Critical Clinical Therapeutic Pathway and an Endogenous Optogenetic Tool for Discovery. Photobiomodul Photomed Laser Surg.
  20. Chen AC et al. 2011. Low-level laser therapy activates NF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts. PLoS One.
  21. Johnstone DM et al. 2014. Indirect application of near infrared light induces neuroprotection in a mouse model of parkinsonism - an abscopal neuroprotective effect. Neuroscience.
  22. Gordon LC et al. 2019. Remote photobiomodulation: an emerging strategy for neuroprotection. Neural Regen Res.
  23. Sanderson TH et al. 2018. Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury. Sci Rep.
  24. Priyadarshi A et al. 2025. Dual near-infrared wavelength photobiomodulation accelerates transdermal burn wound repair via anti-inflammatory, pain relief and redox-regulating mechanisms. J Photochem Photobiol B.
  25. Fu W et al. 2023. 625 nm Light Irradiation Prevented MC3T3-E1 Cells from Accumulation of Misfolded Proteins via ROS and ATP Production. Int J Mol Sci.
  26. Ryu JH et al. 2023. Exploring the Effects of 630 nm Wavelength of Light-Emitting Diode Irradiation on the Proliferation and Migration Ability of Human Biceps Tendon Fibroblast Cells. Clin Orthop Surg.
  27. Priyadarshi A et al. 2023. Dual-NIR wavelength (pulsed 810 nm and superpulsed 904 nm lasers) photobiomodulation therapy synergistically augments full-thickness burn wound healing: A non-invasive approach. J Photochem Photobiol B.
  28. da Silva RLO et al. 2026. Systemic Effects of Vascular Photobiomodulation on Early Macrophage Recruitment During Skeletal Muscle Repair. J Biophotonics.
  29. Pruitt T et al. 2022. Photobiomodulation at Different Wavelengths Boosts Mitochondrial Redox Metabolism and Hemoglobin Oxygenation: Lasers vs. Light-Emitting Diodes In Vivo. Metabolites.
  30. Feng Y et al. 2024. Photobiomodulation Inhibits Ischemia-Induced Brain Endothelial Senescence via Endothelial Nitric Oxide Synthase. Antioxidants (Basel).
  31. Medalha CC et al. 2016. Low level laser therapy accelerates bone healing in spinal cord injured rats. J Photochem Photobiol B.
  32. Wang R et al. 2019. Photobiomodulation for Global Cerebral Ischemia: Targeting Mitochondrial Dynamics and Functions. Mol Neurobiol.
  33. Silva HNMD et al. 2024. LEDT and Idebenone treatment modulate autophagy and improve regenerative capacity in the dystrophic muscle through an AMPK-pathway. PLoS One.
  34. Yang L et al. 2022. Non-invasive photobiomodulation treatment in an Alzheimer Disease-like transgenic rat model. Theranostics.
  35. Duarte KCN et al. 2018. Low-level laser therapy modulates demyelination in mice. J Photochem Photobiol B.
  36. Vieira WF et al. 2022. Anti-hyperalgesic effects of photobiomodulation therapy (904 nm) on streptozotocin-induced diabetic neuropathy imply MAPK pathway and calcium dynamics modulation. Sci Rep.
  37. Comerota MM et al. 2019. Near Infrared Light Treatment Reduces Synaptic Levels of Toxic Tau Oligomers in Two Transgenic Mouse Models of Human Tauopathies. Mol Neurobiol.
  38. Kim K et al. 2019. Photobiomodulation Enhances the Angiogenic Effect of Mesenchymal Stem Cells to Mitigate Radiation-Induced Enteropathy. Int J Mol Sci.
  39. Lovisolo F et al. 2022. Photobiomodulation induces microvesicle release in human keratinocytes: PI3 kinase-dependent pathway role. Lasers Med Sci.
  40. de Paula-Silva M et al. 2020. Red light-emitting diode treatment improves tissue recovery in DSS-induced colitis in mice. J Photochem Photobiol B.
  41. da Rocha RB et al. 2026. Portable Low-Cost Photobiomodulation Device Enhances Migration and Adhesion in L929 Fibroblasts: In Vitro Healing Evidence. J Biophotonics.
  42. Fillipin LI et al. 2005. Low-level laser therapy (LLLT) prevents oxidative stress and reduces fibrosis in rat traumatized Achilles tendon. Lasers Surg Med.
  43. Sassoli C et al. 2016. Low intensity 635 nm diode laser irradiation inhibits fibroblast-myofibroblast transition reducing TRPC1 channel expression/activity: New perspectives for tissue fibrosis treatment. Lasers Surg Med.
  44. Huang YY et al. 2011. Biphasic dose response in low level light therapy - an update. Dose Response.
  45. Ferraresi C et al. 2015. Low-level laser (light) therapy increases mitochondrial membrane potential and ATP synthesis in C2C12 myotubes with a peak response at 3-6 h. Photochem Photobiol.
  46. Huang YY et al. 2013. Low-level laser therapy (LLLT) reduces oxidative stress in primary cortical neurons in vitro. J Biophotonics.
  47. Lanzafame R. 2020. Light Dosing and Tissue Penetration: It Is Complicated. Photobiomodul Photomed Laser Surg.
  48. Hoh Kam J et al. 2023. Glucose Improves the Efficacy of Photobiomodulation in Changing ATP and ROS Levels in Mouse Fibroblast Cell Cultures. Cells.
  49. Shinhmar H et al. 2022. Shifting patterns of cellular energy production (adenosine triphosphate) over the day and key timings for the effect of optical manipulation. J Biophotonics.
  50. Shinhmar H et al. 2021. Weeklong improved colour contrasts sensitivity after single 670 nm exposures associated with enhanced mitochondrial function. Sci Rep.
  51. Shirokov A et al. 2024. Different Effects of Phototherapy for Rat Glioma during Sleep and Wakefulness. Biomedicines.