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Treatment with 670 nm light up regulates cytochrome C oxidase expression and reduces inflammation in an age-related macular degeneration model.

Begum R, Powner MB, Hudson N, Hogg C, Jeffery G - PLoS ONE (2013)

Bottom Line: Inflammation is an umbrella feature of ageing.In ageing and in AMD mitochondrial function declines.Further, inflammation can be reduced independent of Aβ.

View Article: PubMed Central - PubMed

Affiliation: Institute of Ophthalmology, University College London, London, United Kingdom.

ABSTRACT
Inflammation is an umbrella feature of ageing. It is present in the aged retina and many retinal diseases including age-related macular degeneration (AMD). In ageing and in AMD mitochondrial function declines. In normal ageing this can be manipulated by brief exposure to 670 nm light on the retina, which increases mitochondrial membrane potential and reduces inflammation. Here we ask if 670 nm exposure has the same ability in an aged mouse model of AMD, the complement factor H knockout (CFH(-/-)) where inflammation is a key feature. Further, we ask whether this occurs when 670 nm is delivered briefly in environmental lighting rather than directly focussed on the retina. Mice were exposed to 670 nm for 6 minutes twice a day for 14 days in the form of supplemented environmental light. Exposed animals had significant increase in cytochrome c oxidase (COX), which is a mitochondrial enzyme regulating oxidative phosphorylation.There was a significant reduction in complement component C3, an inflammatory marker in the outer retina. Vimetin and glial fibrillary acidic protein (GFAP) expression, which reflect retinal stress in Muller glia, were also significantly down regulated. There were also significant changes in outer retinal macrophage morphology. However, amyloid beta (Aβ) load, which also increases with age in the outer retina and is pro-inflammatory, did not change. Hence, 670 nm is effective in reducing inflammation probably via COX activation in mice with a genotype similar to that in 50% of AMD patients even when brief exposures are delivered via environmental lighting. Further, inflammation can be reduced independent of Aβ. The efficacy revealed here supports current early stage clinical trials of 670 nm in AMD patients.

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Retinal stress is significantly reduced following 670 nm treatment.Vimentin and GFAP are Muller cell markers, which are up regulated in ageing and when the retina is damaged or stressed. A–D. 670 nm treated groups showed significantly reduced vimentin labelling both in terms of length of Muller cells processes (E, p = 0.0001) and their number (F, p = 0.0329). G–J. Shows similar differences for GFAP with a statistically significant reduction following 670 nm treatment (K, p = 0.0001). In both A–D and G–J upper panels are immunostaining alone (red) while in lower panels DAPI is shown as a counter stain (blue). Abbreviations, outer nuclear layer (ONL), outer plexiform layer (OPL), inner plexiform layer (IPL), ganglion cell layer (GCL) and glial fibrillary acidic protein (GFAP). Scale bar A–D = 40 µm.
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pone-0057828-g006: Retinal stress is significantly reduced following 670 nm treatment.Vimentin and GFAP are Muller cell markers, which are up regulated in ageing and when the retina is damaged or stressed. A–D. 670 nm treated groups showed significantly reduced vimentin labelling both in terms of length of Muller cells processes (E, p = 0.0001) and their number (F, p = 0.0329). G–J. Shows similar differences for GFAP with a statistically significant reduction following 670 nm treatment (K, p = 0.0001). In both A–D and G–J upper panels are immunostaining alone (red) while in lower panels DAPI is shown as a counter stain (blue). Abbreviations, outer nuclear layer (ONL), outer plexiform layer (OPL), inner plexiform layer (IPL), ganglion cell layer (GCL) and glial fibrillary acidic protein (GFAP). Scale bar A–D = 40 µm.

Mentions: Staining was present for both vimentin and GFAP in both groups (Figure 6A–D, G–J). However expression of both was down regulated following 670 nm exposure. Vimentin labelling was much more extensive than GFAP in both experimental and control groups. With vimentin the number of Muller cell processes and their length were significantly reduced by 670 nm light (Figure 6E–F). In the untreated group (Figure 6C–D) labelling extended into the outer nuclear layer and was denser at the vitreal surface than in the treated mice. GFAP labelling was also significantly reduced following 670 nm light (Figure 6K), with more label present in the outer retina of controls (Figure 6I–J).


Treatment with 670 nm light up regulates cytochrome C oxidase expression and reduces inflammation in an age-related macular degeneration model.

Begum R, Powner MB, Hudson N, Hogg C, Jeffery G - PLoS ONE (2013)

Retinal stress is significantly reduced following 670 nm treatment.Vimentin and GFAP are Muller cell markers, which are up regulated in ageing and when the retina is damaged or stressed. A–D. 670 nm treated groups showed significantly reduced vimentin labelling both in terms of length of Muller cells processes (E, p = 0.0001) and their number (F, p = 0.0329). G–J. Shows similar differences for GFAP with a statistically significant reduction following 670 nm treatment (K, p = 0.0001). In both A–D and G–J upper panels are immunostaining alone (red) while in lower panels DAPI is shown as a counter stain (blue). Abbreviations, outer nuclear layer (ONL), outer plexiform layer (OPL), inner plexiform layer (IPL), ganglion cell layer (GCL) and glial fibrillary acidic protein (GFAP). Scale bar A–D = 40 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585189&req=5

pone-0057828-g006: Retinal stress is significantly reduced following 670 nm treatment.Vimentin and GFAP are Muller cell markers, which are up regulated in ageing and when the retina is damaged or stressed. A–D. 670 nm treated groups showed significantly reduced vimentin labelling both in terms of length of Muller cells processes (E, p = 0.0001) and their number (F, p = 0.0329). G–J. Shows similar differences for GFAP with a statistically significant reduction following 670 nm treatment (K, p = 0.0001). In both A–D and G–J upper panels are immunostaining alone (red) while in lower panels DAPI is shown as a counter stain (blue). Abbreviations, outer nuclear layer (ONL), outer plexiform layer (OPL), inner plexiform layer (IPL), ganglion cell layer (GCL) and glial fibrillary acidic protein (GFAP). Scale bar A–D = 40 µm.
Mentions: Staining was present for both vimentin and GFAP in both groups (Figure 6A–D, G–J). However expression of both was down regulated following 670 nm exposure. Vimentin labelling was much more extensive than GFAP in both experimental and control groups. With vimentin the number of Muller cell processes and their length were significantly reduced by 670 nm light (Figure 6E–F). In the untreated group (Figure 6C–D) labelling extended into the outer nuclear layer and was denser at the vitreal surface than in the treated mice. GFAP labelling was also significantly reduced following 670 nm light (Figure 6K), with more label present in the outer retina of controls (Figure 6I–J).

Bottom Line: Inflammation is an umbrella feature of ageing.In ageing and in AMD mitochondrial function declines.Further, inflammation can be reduced independent of Aβ.

View Article: PubMed Central - PubMed

Affiliation: Institute of Ophthalmology, University College London, London, United Kingdom.

ABSTRACT
Inflammation is an umbrella feature of ageing. It is present in the aged retina and many retinal diseases including age-related macular degeneration (AMD). In ageing and in AMD mitochondrial function declines. In normal ageing this can be manipulated by brief exposure to 670 nm light on the retina, which increases mitochondrial membrane potential and reduces inflammation. Here we ask if 670 nm exposure has the same ability in an aged mouse model of AMD, the complement factor H knockout (CFH(-/-)) where inflammation is a key feature. Further, we ask whether this occurs when 670 nm is delivered briefly in environmental lighting rather than directly focussed on the retina. Mice were exposed to 670 nm for 6 minutes twice a day for 14 days in the form of supplemented environmental light. Exposed animals had significant increase in cytochrome c oxidase (COX), which is a mitochondrial enzyme regulating oxidative phosphorylation.There was a significant reduction in complement component C3, an inflammatory marker in the outer retina. Vimetin and glial fibrillary acidic protein (GFAP) expression, which reflect retinal stress in Muller glia, were also significantly down regulated. There were also significant changes in outer retinal macrophage morphology. However, amyloid beta (Aβ) load, which also increases with age in the outer retina and is pro-inflammatory, did not change. Hence, 670 nm is effective in reducing inflammation probably via COX activation in mice with a genotype similar to that in 50% of AMD patients even when brief exposures are delivered via environmental lighting. Further, inflammation can be reduced independent of Aβ. The efficacy revealed here supports current early stage clinical trials of 670 nm in AMD patients.

Show MeSH
Related in: MedlinePlus