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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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IBA-1 staining showed significantly different macrophage morphology between 670 nm and control groups.A–D. RPE flat mounts labelled with IBA-1 (green) to identify macrophages. After 14 days of treatment with 670 nm light these cells had significantly altered morphology over a range of metrics. E. Number of IBA-1+ cells per eye was measured; there was a reduction in the number of macrophages following treatment, but this was not statistically significant. F,G. Dendritic process length and area were significantly increased by 670 nm light (27%, 28% respectively) following treatment (p = 0.0001 for each). H. The distance between macrophages was measured from nucleus of one cell to its nearest neighbour, which also showed a significant increase (p = 0.0001). I. Not only were the 670 nm treated cells larger they also had more primary processes (p = 0.05). J. Even though these cells had a greater dendritic field and territory they had smaller cell bodies in comparison to controls (p = 0.05). Abbreviations, retinal pigmented epithelial (RPE), ionized calcium-binding adaptor molecule 1 (IBA-1), macrophages (mφ). Scale bars A, B = 40 µm, C,D = 20 µm.
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pone-0057828-g004: IBA-1 staining showed significantly different macrophage morphology between 670 nm and control groups.A–D. RPE flat mounts labelled with IBA-1 (green) to identify macrophages. After 14 days of treatment with 670 nm light these cells had significantly altered morphology over a range of metrics. E. Number of IBA-1+ cells per eye was measured; there was a reduction in the number of macrophages following treatment, but this was not statistically significant. F,G. Dendritic process length and area were significantly increased by 670 nm light (27%, 28% respectively) following treatment (p = 0.0001 for each). H. The distance between macrophages was measured from nucleus of one cell to its nearest neighbour, which also showed a significant increase (p = 0.0001). I. Not only were the 670 nm treated cells larger they also had more primary processes (p = 0.05). J. Even though these cells had a greater dendritic field and territory they had smaller cell bodies in comparison to controls (p = 0.05). Abbreviations, retinal pigmented epithelial (RPE), ionized calcium-binding adaptor molecule 1 (IBA-1), macrophages (mφ). Scale bars A, B = 40 µm, C,D = 20 µm.

Mentions: IBA-1 is commonly used as a marker of macrophages. IBA-1 positive cells were widely distributed in a relatively uniform pattern over the RPE surface in both experimental and control groups, with somewhat more present in central than peripheral regions (Figure 4A–B). The morphology of the macrophages in the two groups appeared to be markedly different (Figure 4C–D) and although there were less stained cells in the light treated mice, this was not statistically significant (Figure 4E). However, the morphological differences between cells in the two groups were consistently significantly different over a range of metrics.


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)

IBA-1 staining showed significantly different macrophage morphology between 670 nm and control groups.A–D. RPE flat mounts labelled with IBA-1 (green) to identify macrophages. After 14 days of treatment with 670 nm light these cells had significantly altered morphology over a range of metrics. E. Number of IBA-1+ cells per eye was measured; there was a reduction in the number of macrophages following treatment, but this was not statistically significant. F,G. Dendritic process length and area were significantly increased by 670 nm light (27%, 28% respectively) following treatment (p = 0.0001 for each). H. The distance between macrophages was measured from nucleus of one cell to its nearest neighbour, which also showed a significant increase (p = 0.0001). I. Not only were the 670 nm treated cells larger they also had more primary processes (p = 0.05). J. Even though these cells had a greater dendritic field and territory they had smaller cell bodies in comparison to controls (p = 0.05). Abbreviations, retinal pigmented epithelial (RPE), ionized calcium-binding adaptor molecule 1 (IBA-1), macrophages (mφ). Scale bars A, B = 40 µm, C,D = 20 µm.
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Related In: Results  -  Collection

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pone-0057828-g004: IBA-1 staining showed significantly different macrophage morphology between 670 nm and control groups.A–D. RPE flat mounts labelled with IBA-1 (green) to identify macrophages. After 14 days of treatment with 670 nm light these cells had significantly altered morphology over a range of metrics. E. Number of IBA-1+ cells per eye was measured; there was a reduction in the number of macrophages following treatment, but this was not statistically significant. F,G. Dendritic process length and area were significantly increased by 670 nm light (27%, 28% respectively) following treatment (p = 0.0001 for each). H. The distance between macrophages was measured from nucleus of one cell to its nearest neighbour, which also showed a significant increase (p = 0.0001). I. Not only were the 670 nm treated cells larger they also had more primary processes (p = 0.05). J. Even though these cells had a greater dendritic field and territory they had smaller cell bodies in comparison to controls (p = 0.05). Abbreviations, retinal pigmented epithelial (RPE), ionized calcium-binding adaptor molecule 1 (IBA-1), macrophages (mφ). Scale bars A, B = 40 µm, C,D = 20 µm.
Mentions: IBA-1 is commonly used as a marker of macrophages. IBA-1 positive cells were widely distributed in a relatively uniform pattern over the RPE surface in both experimental and control groups, with somewhat more present in central than peripheral regions (Figure 4A–B). The morphology of the macrophages in the two groups appeared to be markedly different (Figure 4C–D) and although there were less stained cells in the light treated mice, this was not statistically significant (Figure 4E). However, the morphological differences between cells in the two groups were consistently significantly different over a range of metrics.

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