670 nm light mitigates oxygen-induced degeneration in C57BL/6J mouse retina

BACKGROUND Irradiation with light wavelengths from the far red (FR) to the near infrared (NIR) spectrum (600 nm -1000 nm) has been shown to have beneficial effects in several disease models. In this study, we aim to examine whether 670 nm red light pretreatment can provide protection against hyperoxia-induced damage in the C57BL/6J mouse retina. Adult mice (90-110 days) were pretreated with 9 J/cm2 of 670 nm light once daily for 5 consecutive days prior to being placed in hyperoxic environment (75% oxygen). Control groups were exposed to hyperoxia, but received no 670 nm light pretreatment. Retinas were collected after 0, 3, 7, 10 or 14 days of hyperoxia exposure (n = 12/group) and prepared either for histological analysis, or RNA extraction and quantitative polymerase chain reaction (qPCR). Photoreceptor damage and loss were quantified by counting photoreceptors undergoing cell death and measuring photoreceptor layer thickness. Localization of acrolein, and cytochrome c oxidase subunit Va (Cox Va) were identified through immunohistochemistry. Expression of heme oxygenase-1 (Hmox-1), complement component 3 (C3) and fibroblast growth factor 2 (Fgf-2) genes were quantified using qPCR. RESULTS The hyperoxia-induced photoreceptor loss was accompanied by reduction of metabolic marker, Cox Va, and increased expression of oxidative stress indicator, acrolein and Hmox-1. Pretreatment with 670 nm red light reduced expression of markers of oxidative stress and C3, and slowed, but did not prevent, photoreceptor loss over the time course of hyperoxia exposure. CONCLUSION The damaging effects of hyperoxia on photoreceptors were ameliorated following pretreatment with 670 nm light in hyperoxic mouse retinas. These results suggest that pretreatment with 670 nm light may provide stability to photoreceptors in conditions of oxidative stress.This work was supported by the Australian Research Council Centre of Excellence in Vision Science

Photobiomodulation protects the retina from light-induced photoreceptor degeneration

Purpose. In this study, the hypothesis that near-infrared (NIR) light treatment (photobiomodulation) attenuates bright-light damage in the albino rat retina was tested. Methods. Young adult Sprague-Dawley (SD) albino rats were raised in dim (5 lux), cyclic light and then exposed to bright (1000 lux), continuous light for 24 hours. The animals were treated with 670-nm light (9 J/cm 2) in an LED array before, during, or after exposure to light. The retinas were examined for function, structural changes, cell loss, and markers of stress and inflammation at 1 week and 1 month after exposure to damaging white light. Results. Bright light caused photoreceptor-specific cell death in control retinas. Significant upregulation of stress and neuroprotective factors and the presence of activated microglia were also noted after light-induced damage. Photobiomodulation profoundly attenuated histopathologic alterations in all three treatment groups. NIR treatment also abolished microglial invasion of the retina and significantly reduced the presence of stress and neuroprotectant molecules. Bright-light-induced reductions in photoreceptor function were significantly ameliorated by photobiomodulation in animals treated before and during exposure to damaging light. Photoreceptor function was initially reduced in animals treated after bright-light-induced damage, but recovered by 1 month after exposure. Conclusions. NIR photobiomodulation is protective against bright-light-induced retinal degeneration, even when NIR treatment is applied after exposure to light. This protective effect appears to involve a reduction of cell death and inflammation. Photobiomodulation has the potential to become an important treatment modality for the prevention or treatment of light-induced stress in the retina. More generally, it could be beneficial in the prevention and treatment of retinal conditions involving inflammatory mechanisms

670-nm light treatment reduces complement propagation following retinal degeneration

AIM Complement activation is associated with the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate whether 670-nm light treatment reduces the propagation of complement in a light-induced model of atrophic AMD. METHODS Sprague-Dawley (SD) rats were pretreated with 9 J/cm(2) 670-nm light for 3 minutes daily over 5 days; other animals were sham treated. Animals were exposed to white light (1,000 lux) for 24 h, after which animals were kept in dim light (5 lux) for 7 days. Expression of complement genes was assessed by quantitative polymerase chain reaction (qPCR), and immunohistochemistry. Counts were made of C3-expressing monocytes/microglia using in situ hybridization. Photoreceptor death was also assessed using outer nuclear layer (ONL) thickness measurements, and oxidative stress using immunohistochemistry for 4-hydroxynonenal (4-HNE). RESULTS Following light damage, retinas pretreated with 670-nm light had reduced immunoreactivity for the oxidative damage maker 4-HNE in the ONL and outer segments, compared to controls. In conjunction, there was significant reduction in retinal expression of complement genes C1s, C2, C3, C4b, C3aR1, and C5r1 following 670 nm treatment. In situ hybridization, coupled with immunoreactivity for the marker ionized calcium binding adaptor molecule 1 (IBA1), revealed that C3 is expressed by infiltrating microglia/monocytes in subretinal space following light damage, which were significantly reduced in number after 670 nm treatment. Additionally, immunohistochemistry for C3 revealed a decrease in C3 deposition in the ONL following 670 nm treatment. CONCLUSIONS Our data indicate that 670-nm light pretreatment reduces lipid peroxidation and complement propagation in the degenerating retina. These findings have relevance to the cellular events of complement activation underling the pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive anti-inflammatory therapy.This work was funded by the Australian Research Council Centres of Excellence Program Grant (CE0561903)

670 nm light mitigates oxygen-induced degeneration in C57BL/6J mouse retina

Background: Irradiation with light wavelengths from the far red (FR) to the near infrared (NIR) spectrum (600 nm -1000 nm) has been shown to have beneficial effects in several disease models. In this study, we aim to examine whether 670 nm red light pretreatment can provide protection against hyperoxia-induced damage in the C57BL/6J mouse retina. Adult mice (90-110 days) were pretreated with 9 J/cm2 of 670 nm light once daily for 5 consecutive days prior to being placed in hyperoxic environment (75% oxygen). Control groups were exposed to hyperoxia, but received no 670 nm light pretreatment. Retinas were collected after 0, 3, 7, 10 or 14 days of hyperoxia exposure (n = 12/group) and prepared either for histological analysis, or RNA extraction and quantitative polymerase chain reaction (qPCR). Photoreceptor damage and loss were quantified by counting photoreceptors undergoing cell death and measuring photoreceptor layer thickness. Localization of acrolein, and cytochrome c oxidase subunit Va (Cox Va) were identified through immunohistochemistry. Expression of heme oxygenase-1 (Hmox-1), complement component 3 (C3) and fibroblast growth factor 2 (Fgf-2) genes were quantified using qPCR.Results: The hyperoxia-induced photoreceptor loss was accompanied by reduction of metabolic marker, Cox Va, and increased expression of oxidative stress indicator, acrolein and Hmox-1. Pretreatment with 670 nm red light reduced expression of markers of oxidative stress and C3, and slowed, but did not prevent, photoreceptor loss over the time course of hyperoxia exposure.Conclusion: The damaging effects of hyperoxia on photoreceptors were ameliorated following pretreatment with 670 nm light in hyperoxic mouse retinas. These results suggest that pretreatment with 670 nm light may provide stability to photoreceptors in conditions of oxidative stress.</p

670-nm light treatment reduces complement propagation following retinal degeneration

AIM: Complement activation is associated with the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate whether 670-nm light treatment reduces the propagation of complement in a light-induced model of atrophic AMD. METHODS: Sprague–Dawley (SD) rats were pretreated with 9 J/cm(2) 670-nm light for 3 minutes daily over 5 days; other animals were sham treated. Animals were exposed to white light (1,000 lux) for 24 h, after which animals were kept in dim light (5 lux) for 7 days. Expression of complement genes was assessed by quantitative polymerase chain reaction (qPCR), and immunohistochemistry. Counts were made of C3-expressing monocytes/microglia using in situ hybridization. Photoreceptor death was also assessed using outer nuclear layer (ONL) thickness measurements, and oxidative stress using immunohistochemistry for 4-hydroxynonenal (4-HNE). RESULTS: Following light damage, retinas pretreated with 670-nm light had reduced immunoreactivity for the oxidative damage maker 4-HNE in the ONL and outer segments, compared to controls. In conjunction, there was significant reduction in retinal expression of complement genes C1s, C2, C3, C4b, C3aR1, and C5r1 following 670 nm treatment. In situ hybridization, coupled with immunoreactivity for the marker ionized calcium binding adaptor molecule 1 (IBA1), revealed that C3 is expressed by infiltrating microglia/monocytes in subretinal space following light damage, which were significantly reduced in number after 670 nm treatment. Additionally, immunohistochemistry for C3 revealed a decrease in C3 deposition in the ONL following 670 nm treatment. CONCLUSIONS: Our data indicate that 670-nm light pretreatment reduces lipid peroxidation and complement propagation in the degenerating retina. These findings have relevance to the cellular events of complement activation underling the pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive anti-inflammatory therapy

The therapeutic potential of 670nm light in retinal degeneration

The retina is susceptible to degenerative changes over the natural life-span, owing to a range of different factors, including genetic susceptibility and environmental and lifestyle factors such as smoking, diet and exposure to bright light. Photoreceptors, with their high metabolic demands and polyunsaturated fatty acid (PUFA)-rich outer segments (OS), are the most vulnerable of retinal cells, being sensitive to oxidative damage and inflammatory attack, resulting in cell death. Because the health and stability of the photoreceptors is essential to the maintenance of functional vision, rescue strategies aimed at stabilising photoreceptors are of critical importance. Exposure to electromagnetic wavelengths in the far-red (FR) to near-infrared (NIR) range (600nm-1000nm) has been reported to have beneficial effects for mammalian tissues in a variety of contexts. These include treatment of soft tissue injuries, radiation-induced ulcers, inflammatory conditions and neurodegenerative diseases. In the recent years, there has been an increasing interest in the use of 670nm red light to manage retinal injuries. The work presented in this thesis examines the effects of exposure to 670nm light in two established models of retinal degeneration in vivo; a light damage (LD) model using Sprague Dawley rats, and an oxygen-induced model of retinal degeneration (hyperoxia) using the C57Bl/6J mouse. The findings indicate that irradiation with 670nm light ameliorates retinal damage in both models, and its effects include modulation of gene expression. In the LD model, irradiation with 670nm light mitigates the damaging effects of white light in a dose-dependent manner, reducing measures of oxidative damage and inflammatory response. In the hyperoxia model, irradiation with 670nm light reduces photoreceptor cell death, mitigates oxidative stress, preserves the integrity of outer retinal barrier and slows down, but does not inhibit, retinal degeneration. The results provide evidence supporting the therapeutic potential of 670nm light in the treatment of retinal degenerative conditions where oxidative stress, cell death and inflammation are involved, particularly in the early stages of degeneration

Treatment with 670-nm light protects the cone photoreceptors from white light-induced degeneration

The light-induced photoreceptor damage model has been used to characterise pathological mechanisms of retinal degenerative diseases and to test potential therapeutic strategies for these conditions. This model is characterised by two fundamental processes that are common to many retinal degenerative conditions; photoreceptor cell death and loss of retinal function. In the present study, we explored the effects of 670-nm light, on cone structure and function using the light damage model in rat retina. Irradiation with 670-nm light has been shown to be beneficial in treating various disease conditions, both in humans and animal models. Sprague-Dawley rats were exposed to bright white light (BL) for 24 h. Animals were divided into three groups (n = 8/group). Each group received 670-nm light treatment at 9 J/cm2 using an LED array 1× daily for 5 days prior to light exposure (pre-conditioned), immediately after cessation of BL for 5 days (post-conditioned) or 1 day prior to BL, then 2× daily during and immediately after BL (mid-conditioned). Assessment of retinal function (ERG), structure (histology), changes in protein expression (immunohistochemistry) and gene expression (RT-qPCR) were evaluated 7 days after light exposure. Damaging effects of white light on the photoreceptor population, function and structure were ameliorated by 670-nm light in the treated groups compared to the non-treated animals (p < 0.05). Present results suggest that treatment with 670-nm light may provide long-term stability of the retina against white light-induced degeneration

670 nm red light preconditioning supports Müller cell function: Evidence from the white light-induced damage model in the rat retina

Glial cells play an important role in the maintenance of normal structure and function of the neural components of the central nervous system. The Müller cells are one of the macroglial elements in the retina and their wide-ranging roles are responsibl

Open Access

670-nm light treatment reduces complement propagation following retinal degeneratio