Photobiomodulation reduces photoreceptor death and regulates cytoprotection in early states of P23H retinal dystrophy

Abstract

Irradiation by light in the far-red to near-infrared (NIR) region of the spectrum (photobiomodulation, PBM) has been demonstrated to attenuate the severity of neurodegenerative disease in experimental and clinical studies. The purpose of this study was to test the hypothesis that 670 nm PBM would protect against the loss of retinal function and improve photoreceptor survival in a rodent model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated once per day with a 670 nm LED array (180 sec treatments at 50 mW/cm 2 ; fluence 9 joules/cm 2) (Quantum Devices Inc., Barneveld WI) from postnatal day (p) 16-20 or from p10-20. Sham-treated rats were restrained, but not exposed to NIR light. The status of the retina was determined at p22 by assessment of mitochondrial function, oxidative stress and cell death. In a second series of studies, retinal status was assessed at p30 by measuring photoreceptor function by ERG and retinal morphology by Spectral Domain Optical Coherence Tomography (SD-OCT). 670 nm PBM increased retinal mitochondrial cytochrome oxidase activity and upregulated the retina's production of the key mitochondrial antioxidant enzyme, MnSOD. PBM also attenuated photoreceptor cell loss and improved photoreceptor function. PBM protects photoreceptors in the developing P23H retina, by augmenting mitochondrial function and stimulating antioxidant protective pathways. Photobiomodulation may have therapeutic potential, where mitochondrial damage is a step in the death of photoreceptors.

Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa

“…This finding indicates that both mitochondrial dysfunction and mitochondrial oxidative stress are significant early cellular events in this model of RP. These findings confirm and extend previous studies in P23H rats 32,33 and other disease states [45][46][47]49 . Moreover, these findings are in agreement with those obtained from proteomic profiling of Drosophila melanogaster retinas expressing the Rho P23H equivalent mutation Rh1 P37H and suggest that energetic and metabolic dysfunction are a critical link between rhodopsin misfolding/proteotoxicity and photoreceptor degeneration in RP 36 .…”

“…The electroretinogram (ERG) is a functional measure of outer retinal activity in response to light 30 . Both the a-wave (photoreceptor response) and b-wave (bipolar cell and Muller glial cell response) were significantly attenuated in the P23H retina compared with the non-dystrophic SD retina consistent with other studies and the pathology of the disease 32,46 . 830 nm PBM treatment improved the b-wave response at low stimulus intensities and the a and b wave responses at higher stimulus intensities.…”

“…In neural tissue, cytochrome c oxidase is the most abundant metalloprotein and wavelength peaks in its absorption spectrum (670 nm and 830 nm) highly correlate with its peaks in catalytic activity and with ATP content in vitro 53 . The degree of functional protection that we observed with 830 nm PBM treatment in P23H rats is comparable to the degree of functional protection reported by Kirk et al 32 in the 670 nm PBM-treated P23H rat and by Albarracin et al 46 in a 670 nm PBM-treated lightinduced retinal degeneration model indicating that both FR and NIR light are retinoprotective.…”

“…They provided the first link between the effects of FR light on mitochondrial bioenergetics in vitro and retinoprotection in vivo. Subsequent studies have established the retinoprotective effects of FR PBM (630-680 nm) in rodent models of diabetic retinopathy, AMD, and RP [25][26][27][28]32 .…”

Retinal pigment epithelium in the pathogenesis of age‐related macular degeneration and photobiomodulation as a potential therapy?

“…More recently, focus has turned to the potential beneficial effects of photobiomodulation as a treatment for blinding retinal diseases. Treatment effects from photobiomodulation has been demonstrated in various retinal disease animal models including light‐induced retinal degeneration, AMD, retinitis pigmentosa, diabetic retinopathy and retinopathy of prematurity as evidenced by improved ERG, decreased inflammatory markers and diminished cell loss.…”