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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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Amyloid beta expression is unaffected by 670 nm treatment.A.B. Aβ (red) expression was measured at the Bruch’s membrane/RPE interface and this was unchanged between experimental and control groups as shown in C. Abbreviation, amyloid beta (Aβ), Bruch’s membrane (BM), retinal pigmented epithelium (RPE). Scale bar A–B = 40 µm.
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pone-0057828-g007: Amyloid beta expression is unaffected by 670 nm treatment.A.B. Aβ (red) expression was measured at the Bruch’s membrane/RPE interface and this was unchanged between experimental and control groups as shown in C. Abbreviation, amyloid beta (Aβ), Bruch’s membrane (BM), retinal pigmented epithelium (RPE). Scale bar A–B = 40 µm.

Mentions: With age, the outer retina accumulates Aβ mainly on Bruch’s membrane and on photoreceptor outer segments [2]. This age related deposit is pro-inflammatory. Aβ was measured on Bruch’s membrane in both experimental and control group (Figure 7A–B). Measurements of staining intensity made at this interface showed no difference in deposition between the two groups (Figure 7C).


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)

Amyloid beta expression is unaffected by 670 nm treatment.A.B. Aβ (red) expression was measured at the Bruch’s membrane/RPE interface and this was unchanged between experimental and control groups as shown in C. Abbreviation, amyloid beta (Aβ), Bruch’s membrane (BM), retinal pigmented epithelium (RPE). Scale bar A–B = 40 µm.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0057828-g007: Amyloid beta expression is unaffected by 670 nm treatment.A.B. Aβ (red) expression was measured at the Bruch’s membrane/RPE interface and this was unchanged between experimental and control groups as shown in C. Abbreviation, amyloid beta (Aβ), Bruch’s membrane (BM), retinal pigmented epithelium (RPE). Scale bar A–B = 40 µm.
Mentions: With age, the outer retina accumulates Aβ mainly on Bruch’s membrane and on photoreceptor outer segments [2]. This age related deposit is pro-inflammatory. Aβ was measured on Bruch’s membrane in both experimental and control group (Figure 7A–B). Measurements of staining intensity made at this interface showed no difference in deposition between the two groups (Figure 7C).

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