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Dovepress Table 2 Beneficial in vivo effects of low-level light therapy on the eye Low-level light therapy Reference Schwartz et al,71 Assia et al,72 Eells et al,12 Rojas et al,49 Eells et al,76 Eells et al,76 Qu et al,73 Rodriguez-Santana et al,77 Light source He-Ne laser GaAlAs LED GaAlAs LED GaAlAs LED GaAlAs LED GaAlAs LED iLPD Wavelength 632.8 nm 670 nm 633 nm 670 nm 670 nm 670 nm 904 nm Dose 10.5 mw, 1.1 mm beam diameter × 2 minutes, daily for 2 weeks 28 mw/cm2, 12 J/cm2 in three fractions 2 mw/cm2, 21.6 J/cm2 in six fractions 16 J/cm2 in four fractions 50 mw/cm2, 20 J/cm2 in five fractions 50 mw/cm2, 360 J/cm2 in four fractions 4500 mw/cm2, 45,000 J/m2, pulsed at 3 MHz Effect Preserved structure and function after optic nerve crushed injury (rat, rabbit) Preserved structure and function after systemic methanol photoreceptor toxicity (rat) Preserved structure and function after intravitreal rotenone injection (rat) Preserved structure and function after laser retinal photocoagulation (monkey) Preserved structure in the P23H-3 rat (rat) Preserved structure and function after phototoxicity (rat) improved function in an 86-year- old man with macular degeneration (human) Relevance Optic nerve trauma Methanol intoxication Leber’s hereditary optic neuropathy Laser-induced retinal injury Retinitis pigmentosa Light-induced retinal damage Age-related macular degeneration Abbreviations: GaAlAs LED, Gallium-Aluminum-Arsenide light-emitting diode; He-Ne, Helium-Neon; iPLD, intense pulsed light device. spectrum.78 Photons at wavelengths between 630 nm and 800 nm have been shown to travel up to 28 mm even in lay- ers of tissues with relatively low transparencies such as skin, connective tissue, muscle, bone, and spinal cord, with about 6% of the total energy density being detectable at the ventral surface of a living rat.42,80 In gray matter, red and near-infrared light penetration is governed by Beer–Lambert law, with the optical power decaying up to 80% at 1 mm from the surface.81 However, at this depth in solid organs, the actual power density of near-infrared light has been estimated to be up to three times higher than the power at the incident surface due to backscattering and constructive interference.82 As the light travels into the tissue, its intensity decreases due to absorption and scattering. Penetration of light into tissues depends not only on the wavelength but also on the optical properties of the target tissue. The maximal penetration of light in the gray and white matter of the brain occurs at wavelengths in the near-infrared spectrum.81 It has been shown that within the visible and near-infrared spectral range, white matter in both the central and peripheral nervous systems reflects most of the incident power and shows a low level of absorption and a short penetration depth.83 In contrast, the transmittance of the gray matter is approximately twice as high as that of the white matter (Figure 2). Finally, the penetration of light is not only contingent on the wavelength or the specific tissue, but significant interspecies differences in penetration have also been detected. For example, at 850 nm, the penetration of energy in humans is almost three times higher than that in the mouse cortex.81 While the cause of this significant difference Eye and Brain 2011:3 of light-tissue interaction can be explained by differences in water and protein content, this observation has obvious translational implications that should be considered when LLLT data generated in animal models is applied to humans. Finally, the delivery modality of LLLT is also relevant to transcranial in vivo applications (Table 1). For example, noncontact delivery modalities with LEDs allow exposure of extensive surfaces, including whole-body treatments. LEDs montages can potentially be built with ergonomic consider- ations for whole-head and whole-body LLLT in humans. In contrast, contact modalities combined with laser sources may be ideal when localized energy delivery is needed. This may be advantageous for boosting cell functions in specific nodes within dysfunctional neural networks in which connectivity could be otherwise impaired with broad irradiation. Similarly, localized transcranial LLLT may be of use for neuroprotec- tion of healthy tissue adjacent to tumor sites after resection, without risk of inducing photobiomodulation of residual tumor. The eyes always need to be appropriately protected from laser light in transcranial applications. Rojas et al49 were the first to demonstrate that upon transcranial delivery in vivo, LLLT induces whole-brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dis- mutase activities. Increases in cerebral blood flow induced by LLLT have also been observed in humans when applied transcranially.84 It is possible that these effects are related to a number of neuroprotective and function-enhancing effects that have been observed with the use of LLLT submit your manuscript | www.dovepress.com Dovepress 61PDF Image | Low-level light therapy of the eye and brain
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