The phenotype in ESCS is variable, both in fundus appearance and in the severity of the electrophysiological abnormalities. The ERGs are dominated by short-wavelength-sensitive mechanisms. The presence, in most of the patients, of possible OFF-related ERG activity is a finding not usually associated with S-cones.
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.
Progressive accumulation of age related mitochondrial DNA mutations reduce ATP production and increase reactive oxygen species output, leading to oxidative stress, inflammation and degradation. The pace of this is linked to metabolic demand. The retina has the greatest metabolic demand and mitochondrial density in the body and displays progressive age related inflammation and marked cell loss. Near infra-red (670 nm) is thought to be absorbed by cytochrome c oxidase (COX), a key element in mitochondrial respiration and it has been demonstrated that it improves mitochondrial membrane potentials in aged eyes. It also significantly reduces the impact of experimental pathology and ameliorates age related retinal inflammation. We show ATP decline with ageing in mouse retina and brain. Also, in these tissues that ATP is significantly increased by 670 nm exposure in old mice. In the retina this was associated with increased COX and reduced acrolein expression. Acrolein, being a free radical marker of retinal oxidative stress, is up regulated in Alzheimer's and retinal degeneration. This is the first demonstration of ATP manipulation in vivo and may provide a simple non-invasive route to combating age related tissue decline.
The PERG evoked by black-and-white patterns is partly pattern specific and partly evoked by local changes in luminance. When a chequerboard reverses, the increase in brightness of part of the screen is exactly matched by decreases in other parts. It follows that the average response of many different
SUMMARYThe Arctic has extreme seasonal changes in light levels and is proportionally UV-rich because of scattering of the shorter wavelengths and their reflection from snow and ice. Here we show that the cornea and lens in Arctic reindeer do not block all UV and that the retina responds electrophysiologically to these wavelengths. Both rod and cone photoreceptors respond to UV at low-intensity stimulation. Retinal RNA extraction and in vitro opsin expression show that the response to UV is not mediated by a specific UV photoreceptor mechanism. Reindeer thus extend their visual range into the short wavelengths characteristic of the winter environment and periods of extended twilight present in spring and autumn. A specific advantage of this short-wavelength vision is the use of potential information caused by differential UV reflections known to occur in both Arctic vegetation and different types of snow. UV is normally highly damaging to the retina, resulting in photoreceptor degeneration. Because such damage appears not to occur in these animals, they may have evolved retinal mechanisms protecting against extreme UV exposure present in the daylight found in the snow-covered late winter environment.
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