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This comparative study was designed to evaluate effect of low-intensity speckle laser radiation in the green and red wavelengths on intraocular hemodynamics in patients eyes with retinal vascular problems and without them. Peak systolic velocity and peripheral resistance index in posterior short ciliary arteries and central retinal artery were measured. It was shown for the first time that green speckle laser radiation wavelength nm has more pronounced compared with the red light effect on intraocular hemodynamics; thereby, it makes a greater contribution to the improvement of the visual function e.
Analyzed the data: TK YD. Wrote the paper: TK. Daily application of prostatilen Injektion Wales light from the onset of diabetes mitigated diabetes-induced abnormalities prostatilen Injektion Wales retinas of albino rats.
Here, we test the hypothesis that photobiomodulation PBM is effective in diabetic, pigmented mice, even when delayed until weeks after onset of prostatilen Injektion Wales. Direct and indirect effects of PBM on the retina also were studied. Prostatilen Injektion Wales one study, mice were diabetic for 4 weeks before initiation of PBM for an additional 10 weeks. Retinal oxidative stress, inflammation, and retinal function were measured.
In some mice, heads were covered with a lead shield during PBM to prevent direct illumination of the eye, or animals were treated with an inhibitor of heme oxygenase In a second study, PBM was initiated immediately after onset of diabetes, and administered daily for 2 months.
These mice were examined using manganese-enhanced MRI to assess effects of PBM on transretinal calcium channel function in vivo. PBM prostatilen Injektion Wales improved diabetes-induced changes in superoxide generation, leukostasis, expression of ICAM-1, and visual performance. PBM acted in part remotely from the retina because the beneficial effects were achieved even with the head shielded from the light therapy, and because leukocyte-mediated cytotoxicity of retinal endothelial cells was less in diabetics treated with PBM.
In study 2, PBM largely mitigated diabetes-induced retinal calcium channel dysfunction prostatilen Injektion Wales all retinal layers. PBM induces retinal protection against abnormalities induced by diabetes in prostatilen Injektion Wales animals, and even as an intervention.
Beneficial effects on the retina likely are mediated by both direct and indirect mechanisms. PBM is a novel non-pharmacologic treatment strategy to inhibit early changes of diabetic retinopathy.
Diabetes is a major cause of visual impairment, and there is considerable clinical and research interest in diabetic retinopathy.
Proven therapeutic approaches, such as good glycemic control, high energy laser photocoagulation, or intravitreal injections of anti-VEGF therapies or triamcinolone, are invasive, damaging, or require direct prostatilen Injektion Wales by health-care professionals, and not all patients respond to these approaches. Supplemental therapeutic approaches are needed. Photobiomodulation PBM is the application of low-level light that has a biological effect, such as to relieve pain or heal wounds.
Numerous studies have shown that light in the far-red to near-infrared region of the spectrum — nm can prostatilen Injektion Wales beneficial effects in vitro and in vivo prostatilen Injektion Wales heal existing tissue damage and to inhibit the development of tissue pathology. Studies related to the retina likewise have demonstrated that the low intensity light treatment mitigates pathology in retinal degeneration models [ 413 — 16 ], and recently, also in diabetic retinopathy [ 17prostatilen Injektion Wales ].
Our previous study in diabetic albino rats showed that whole-body exposure to far-red light nm for only 4 minutes per day from the onset of diabetes mitigated abnormalities that are believed to contribute to diabetic retinopathy, including increased generation of superoxide, induction of a local pro-inflammatory environment, and dysfunction or degeneration of retinal neurons [ 18 ].
Our results suggest that the PBM has both neuronal and vascular beneficial effects on pigmented diabetic mice, and that this effect is mediated at least in part systemically. Animals were housed and maintained in normal 12hh light-dark cycle laboratory lighting. Insulin was given as 0—0. Prostatilen Injektion Wales allow the animals to stabilize somewhat after induction of diabetes, blood glucose concentration was not prostatilen Injektion Wales until at least 7 days after the final administration of streptozotocin.
Blood glucose was determined with a portable glucose meter, using blood collected from the tail vein under nonfasting conditions. HbA1c was measured as reported previously Study 1 [ 19 prostatilen Injektion Wales, 20 ]; Study 2 [ 21 ].
There were two parts to this work. All animals were euthanized at 14 weeks of diabetes 5—6 months of age. These animals were humanely euthanized at 8 weeks of diabetes. This device was determined to deliver nm light at a power prostatilen Injektion Wales Prostatilen Injektion Wales mice were exposed to this radiation for sec each day for the 10 weeks.
The daily radiant prostatilen Injektion Wales was thus x To ensure that the polypropylene bag would not impair passage of the red light, transmittance through the bag was tested; compared to the air, one layer of the plastic used to restrain the animals absorbed 8.
Intervention with PBM treatment was started four weeks after the onset of diabetes, and was continued for ten additional weeks. To minimize handling, animals in study 2 were allowed free movement in a small space during PBM.
PBM was started immediately after confirmation of diabetes in this experimental study. Fresh retinas prostatilen Injektion Wales animals were analyzed for prostatilen Injektion Wales production as previously described [ 182324 ]. Briefly, retinas were placed in 0. To each tube, 0. Louis, MO was added and incubated for an additional 10 minutes before having the photon emission detected by a luminometer Analytical Luminescence Laboratory, San Diego, CA.
Retinal protein was quantified Bio-Radand the luminescence prostatilen Injektion Wales per mg of protein. Prostatilen Injektion Wales SnPP was freshly made dissolved in 0. Mice received ? Blood was removed from the vasculature of anesthetized animals by perfusion with phosphate-buffered saline PBS; 10 mM phosphate buffer, 2. Louis, MO via a heart catheter. Animals were then perfused with fluorescein-coupled concanavalin A lectin 20?
Flat-mounted retinas were imaged via fluorescence microscopy, and the number of leukocytes adherent to the vascular wall was counted. The virtual optokinetic system OptoMetry; CerebralMechanics, Inc, was used as described previously [ 1927 ].
At 14 weeks of diabetes, prostatilen Injektion Wales were allowed to move freely on the platform of the visual OptoMotor system while the prostatilen Injektion Wales stimulus was projected around the platform. Spatial frequency threshold was measured at maximum contrast.
For contrast sensitivity, only a single value 0. These tests are psychophysical measures that assess function of both retinal and central visual pathways. Each measurement was repeated several times to evaluate the reproducibility of responses. The retina or cells was isolated and placed into 80? After incubation, the leukocytes were carefully removed by gentle washing, and viability of remaining retinal endothelial cells was measured by trypan blue exclusion.
Cell death was reported as the percentage of blue-stained cells dead cells of the total number of cells. Approximately — cells were counted in each sample.
The resolution obtained in the central retina is sufficient for extracting meaningful layer-specific anatomical and functional data, as previously discussed [ 3637 ]. We rely on the well-defined laminar structure of the retina to distinguish, for example, inner retinal uptake from outer retinal uptake. Comparisons of MEMRI data between groups were performed prostatilen Injektion Wales individual t-tests at different locations of the intraretinal profiles; those selected regions identified from the t-tests as significant were then analyzed using GEE [ 3738 ].
After injection with STZ, the presence of diabetes prostatilen Injektion Wales confirmed based on blood glucose levels and body weight. Over the weeks of diabetes, the mean blood glucose level, HbA1c and body weight were significantly different between STZ-treated mice and control mice Tables? Tables1 1 and? Prostatilen Injektion Wales treatment had no significant effect on body weight, non-fasting blood glucose or HbA1c compared to the other diabetic groups. Diabetes of 2 months duration also significantly impaired visual function, as assessed from spatial frequency threshold and contrast sensitivity measured at a single point; 0.
Although initiation of the PBM therapy in these pigmented animals was delayed for 1 month of untreated diabetes, the prostatilen Injektion Wales intervention with PBM therapy nevertheless significantly mitigated many of these defects.
The light therapy had no significant effect on the diabetes-induced changes in retinal iNOS or HO-1 prostatilen Injektion Wales defect in contrast sensitivity measured in these samples.
In vitro studies previously showed that incubation of retinal cells in 30 mM glucose caused a significant reduction in HO-1 expression, and that PBM significantly inhibited this reduction [ 18 ]. Pharmacologic inhibition of Prostatilen Injektion Wales in vivo completely prevented the benefits of PBM in the diabetes-induced increase in retinal leukostasis Fig 1suggesting that the beneficial effect of PBM prostatilen Injektion Wales leukocyte adhesion required HO Administration of SnPP to PBM-treated diabetics had no significant effect on spatial frequency threshold or single point contrast sensitivity compared prostatilen Injektion Wales animals treated with PBM only not shown.
To test if some of the observed beneficial effects of PBM on retina were mediated systemically, an opaque lead head shield was used to prevent direct irradiation to the eye.
Neither retinal superoxide production, leukostasis, prostatilen Injektion Wales Figs? Figs1 1 and? We previously have found that leukocytes play a major prostatilen Injektion Wales in diabetes-induced degeneration of retinal capillaries [ 2339 ]. Consistent with our prior reports, prostatilen Injektion Wales from control diabetics not treated with PBM caused significantly more endothelial cytotoxicity in co-cultures than did leukocytes from nondiabetic animals Fig 3.
Intervention with PBM for only 4 prostatilen Injektion Wales per day totally suppressed the diabetes-induced killing of retinal endothelial cells by leukocytes from diabetic prostatilen Injektion Wales. As previously reported [ 2133 ], diabetes reduced manganese uptake across the retina in the dark compared with non-diabetic mice Fig 4.
PBM-treated diabetic mice exhibited largely normal calcium channel function in all layers of the retina, except in the presumptive rod inner segment layer. PBM is a novel therapeutic approach to mitigate the development of diabetic retinopathy, and preliminary studies in diabetic rodents and patients have shown promise [ 1718 ].
Of note, the therapy is easy to administer, and the beneficial effects were detected at a low amount of daily radiant exposure. We demonstrate herein that the beneficial effects of PBM are mediated at least in part via indirect effects, and occur even if the initiation of therapy is delayed post-conditioning. We used a head shield to determine if observed beneficial effects of PBM on the retina required direct illumination of the retina. The diabetic mice that had their heads covered to prevent light from reaching the eyes for the 4 min of illumination nevertheless showed beneficial effects of the PBM treatment with respect to superoxide generation, leukostasis, expression of inflammatory proteins, and visual function.
Indirect effects of PBM detected also in other studies include where treatment of one side of the body had beneficial effects also on the untreated side with prostatilen Injektion Wales to skin blood flow, temperature in the feet prostatilen Injektion Wales diabetic patients [ 42 ], or healing of skin wounds and burns [ 4344 ].
Previously reported beneficial effects of PBM in kidney and heart [ 78 ] of diabetic animals are consistent with PBM exerting at least some effects via systemic mediators, but far-red light is known to penetrate deeply into tissues, and prostatilen Injektion Wales might directly irradiate those tissues. The molecular and cellular changes initiated by PBM which mediate observed beneficial effects are under investigation.
Mitochondrial cytochrome c oxidase is often considered to be a target of PBM therapy [ 15 prostatilen Injektion Wales, 45 — 47 ], although a recent study from our group did not find evidence to support this in the retina prostatilen Injektion Wales diabetic rats [ 18 ]. Intriguingly, MEMRI studies showed that PBM did not inhibit diabetes-induced defects in ion movement in the inner segment layer of retinal photoreceptors, the region that contains the majority of retinal mitochondria. Thus our findings prostatilen Injektion Wales suggest that PBM exerts beneficial effects that are independent of photoreceptor mitochondria.
In addition, several studies have demonstrated that PBM can activate stem cells to proliferate [ 48 — 50 ]. This might be relevant, since release of stem cells and progenitor cells from bone marrow is impaired in diabetes [ 51 — 54 ], and administration of stem cells to diabetic animals inhibits lesions of the retinopathy prostatilen Injektion Wales 55 ]. PBM imparts significant anti-oxidant benefits in retinas of diabetic albino rats and in pigmented mice.
Whether this is mediated via direct or indirect mechanisms is not known, but it is clear that increased retinal oxidative stress is a major contributor to the pathogenesis of diabetic retinopathy.