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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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Outer retinal inflammation is significantly reduced following 670 nm treatment.A.B. Retinal sections stained with C3 (red). This accumulates on Bruch’s membrane and outer segments. C.D Following 670 nm treatment C3 was significantly reduced on Bruch’s membrane and photoreceptor outer segments (p = 0.0001 for each). E. These data were confirmed with qPCR analysis, which showed again a statistically significant reduction in C3 expression following treatment (p = 0.0031). Abbreviations, Bruch’s membrane (BM), photoreceptor (PR), complement component (C3). Scale bars = 40 µm.
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pone-0057828-g005: Outer retinal inflammation is significantly reduced following 670 nm treatment.A.B. Retinal sections stained with C3 (red). This accumulates on Bruch’s membrane and outer segments. C.D Following 670 nm treatment C3 was significantly reduced on Bruch’s membrane and photoreceptor outer segments (p = 0.0001 for each). E. These data were confirmed with qPCR analysis, which showed again a statistically significant reduction in C3 expression following treatment (p = 0.0031). Abbreviations, Bruch’s membrane (BM), photoreceptor (PR), complement component (C3). Scale bars = 40 µm.

Mentions: The inflammatory marker C3 normally accumulates with age on Bruch’s membrane and on photoreceptor outer segments. C3 immunostaining was significantly lower in 670 nm treated mice at both locations than in controls (Figure 5A–D). On Bruch’s membrane it was almost halved, and on outer segments the reduction was approximately 20%. To confirm this finding C3 expression was also measured with qPCR, and again there was a significant reduction following 670 nm treatment with expression level halving (Figure 5E).


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)

Outer retinal inflammation is significantly reduced following 670 nm treatment.A.B. Retinal sections stained with C3 (red). This accumulates on Bruch’s membrane and outer segments. C.D Following 670 nm treatment C3 was significantly reduced on Bruch’s membrane and photoreceptor outer segments (p = 0.0001 for each). E. These data were confirmed with qPCR analysis, which showed again a statistically significant reduction in C3 expression following treatment (p = 0.0031). Abbreviations, Bruch’s membrane (BM), photoreceptor (PR), complement component (C3). Scale bars = 40 µm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585189&req=5

pone-0057828-g005: Outer retinal inflammation is significantly reduced following 670 nm treatment.A.B. Retinal sections stained with C3 (red). This accumulates on Bruch’s membrane and outer segments. C.D Following 670 nm treatment C3 was significantly reduced on Bruch’s membrane and photoreceptor outer segments (p = 0.0001 for each). E. These data were confirmed with qPCR analysis, which showed again a statistically significant reduction in C3 expression following treatment (p = 0.0031). Abbreviations, Bruch’s membrane (BM), photoreceptor (PR), complement component (C3). Scale bars = 40 µm.
Mentions: The inflammatory marker C3 normally accumulates with age on Bruch’s membrane and on photoreceptor outer segments. C3 immunostaining was significantly lower in 670 nm treated mice at both locations than in controls (Figure 5A–D). On Bruch’s membrane it was almost halved, and on outer segments the reduction was approximately 20%. To confirm this finding C3 expression was also measured with qPCR, and again there was a significant reduction following 670 nm treatment with expression level halving (Figure 5E).

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