PDF Publication Title:
Text from PDF Page: 010
International Journal of Photoenergy 9 experiments where animals were treated with 90 J/cm2 in the absence of light damage (Figure 4). An unexpected finding is that high doses of 670 nm light (90 J/cm2 ) reduced the levels of photoreceptor death when the light damage stimulus is of a high intensity (Figure 1(a) light grey, dotted line, Figure 1(d)). These data indicate that the level of protection afforded by 670 nm light is dependent on the degree of damage done to the retina. This interplay between retinal damage and effective 670 nm dose has not been identified previously. Favourable outcomes of 670 nm light treatment for retinal degeneration models have typically used a dose of 9J/cm2 in a 1000- lux light damage paradigm and show reduced photoreceptor cell death, downmodulation of inflammatory factors, and indicators of oxidative stress [22–24, 33]. Protective effects using 90 J/cm2 670 nm light have been reported in the retina previously in a higher intensity light damage paradigm (1800 lux) [25]. Those findings are consistent with our present findings and support the concept that higher doses of 670 nm light are required as a therapeutic dose to treat highly stressed/damaged retinas. It is important to note that the high dose of 90 J/cm2 used might be preconditioning the retina to retinal stress, thereby protecting the retina against further stress. The dose-response of the retina to 670 nm light is consis- tent with the concept of hormesis (reviewed in [36, 37]), that is, a biphasic dose-response to an environmental agent that is stimulatory at low doses, and inhibitory at high doses. 4.2.MetabolicEffectsof670nmLight. Evidenceoftheroleof cytochrome c oxidase activity being modulated by red light has been shown by exposing cells to high-fluence, low-power laser irradiation 635nm lasers, causing photoinactivated respiratory chain oxidase to trigger a fatal mitochondrial superoxide burst [38, 39]. Previous in vitro studies have reported increases in cytochrome c oxidase activity, mito- chondrial metabolism, and ATP production, after irradiation with red/near-infrared light [27, 28, 30, 40, 41], although the mechanisms generating these effects have not been identified. Although we did not detect any changes in ATP pro- duction by 661 W photoreceptor-like cells using the Seahorse XFe96 Extracellular Flux Analyzer, a change in the spare respiratory capacity of the cells was observed. We detected a 31% increase in spare respiratory capacity in cells treated with 670 nm light, compared with untreated cells. Control, nonlight damaged cells also exhibited an increase in the spare respiratory capacity when treated with 670 nm light. Spare respiratory capacity of a cell is critical when a sudden burst of energy is required to survive critical stress conditions and is important in the long-term viability of cells [42]. Spare respiratory capacity depletion has been implicated in various disease conditions including heart diseases [43], neurodegenerative disorders [44, 45], and cell death in smooth muscle [46], but its significance in retinal metabolism is yet to be established. The measurable increase in spare respiratory capacity identified in the present study helps substantiate claims of a role for the mitochondria, and specifically cytochrome c oxidase, in 670 nm light therapy [27–31, 47]. We hypothesize that this increase in spare respiratory capacity is the precursor to an increase in ATP production demonstrated in a number of other models [30, 41]; however this increase in ATP is only evident when required by the cells. We suspect that an increase in ATP was not observed here, as the damage stimulus that we had applied was not severe enough to warrant this biological change. The data also indicated a 23% increase in nonmitochon- drial respiration in 670 nm light treated cells, compared to controls. A number of factors can contribute to nonmito- chondrial respiration [48]. In the present context, it is pos- sible that nonmitochondrial respiration is reduced by light damage as a result of decreased efficiency of detoxifying and ROS-scavenging enzymes and that treatment with 670 nm light restores those functions, increasing nonmitochondrial respiration. However, we detected no alteration in H2O2 output between light damaged 661W cells, treated versus untreated, or any protection against cell death in the 670 nm light treated cells. The literature includes conflicting reports with regard to changes in ROS levels following red light treatment (reviewed in [21]). In the present study, to our surprise, our in vitro experiments detected no changes in cell death levels but did demonstrate an increase in spare respiratory capacity in 661 W cells. Our data indicate that the effects of 670 nm light treatment may be dependent on the experimental environ- ment, involving processes that occur in tissues comprising mixed cell populations (as occurs in vivo), as distinct from a monoculture environment (as in vitro). This may explain why we see a protective function for 670 nm light treatment in vivo, but no changes in cell death rates in 670 nm light treated cells in vitro. 4.3. Possible Mechanism of 670nm Light. Cytochrome c oxidase is complex IV of the mitochondrial electron transport chain and is the immediate regulator of oxidative phosphory- lation tightly controlling the production of ATP [49]. Nitric oxide (NO) has the ability to bind to the oxygen-binding site of cytochrome c oxidase, which allows it to inhibit the action of cytochrome c oxidase by competing with molec- ular oxygen for the respective binding site. This reversible inhibition of complex IV by NO has been shown to occur at nanomolar levels, suggesting that NO may be a regulator of respiration by reducing the rate of ATP production [50– 53]. One possibility that has been canvassed previously is that 670 nm light releases NO from cytochrome c oxidase, allowing for an increased rate of oxidative phosphorylation and ATP production [54–56]. Not only will this directly allow for increased respiration due to an increased action of cytochrome c oxidase, but NO may also act as a downstream signaling molecule and vasodilator [54, 57, 58]. Therefore, this release of NO may also allow for a more rapid rate of oxygen delivery for phosphorylation as a further downstream effect [54]. We hypothesize that the increase in spare respiratory capacity detected in cells treated 670 nm light in this study is a result of NO release from cytochrome c oxidase inPDF Image | 670 nm Light Therapy to Protect vs Photoreceptor Cell Death
PDF Search Title:
670 nm Light Therapy to Protect vs Photoreceptor Cell DeathOriginal File Name Searched:
Efficacy_of_670_nm_Light_Therapy_to_Protect_agains.pdfDIY PDF Search: Google It | Yahoo | Bing
Cruise Ship Reviews | Luxury Resort | Jet | Yacht | and Travel Tech More Info
Cruising Review Topics and Articles More Info
Software based on Filemaker for the travel industry More Info
The Burgenstock Resort: Reviews on CruisingReview website... More Info
Resort Reviews: World Class resorts... More Info
The Riffelalp Resort: Reviews on CruisingReview website... More Info
CONTACT TEL: 608-238-6001 Email: greg@cruisingreview.com (Standard Web Page)