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Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect Mechanisms: Evidence from Intervention Studies in Pigmented Mice.

Saliba A, Du Y, Liu H, Patel S, Roberts R, Berkowitz BA, Kern TS - PLoS ONE (2015)

Bottom Line: 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.SnPP+PBM significantly reduced iNOS expression compared to PBM alone, but significantly exacerbated leukostasis.Beneficial effects on the retina likely are mediated by both direct and indirect mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Case Western Reserve University, Cleveland, Ohio, United States of America; Catholic University of Brasilia, Brasilia, Brazil.

ABSTRACT

Objective: Daily application of far-red light from the onset of diabetes mitigated diabetes-induced abnormalities in 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 diabetes. Direct and indirect effects of PBM on the retina also were studied.

Methods: Diabetes was induced in C57Bl/6J mice using streptozotocin. Some diabetics were exposed to PBM therapy (4 min/day; 670 nm) daily. In 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-1. 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.

Results: PBM intervention 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. SnPP+PBM significantly reduced iNOS expression compared to PBM alone, but significantly exacerbated leukostasis. In study 2, PBM largely mitigated diabetes-induced retinal calcium channel dysfunction in all retinal layers.

Conclusions: PBM induces retinal protection against abnormalities induced by diabetes in pigmented 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.

No MeSH data available.


Related in: MedlinePlus

Intervention with PBM mitigates leukocyte-mediated cytotoxicity of endothelial cells caused by leukocytes from diabetic animals.Co-culture of transformed mouse retinal endothelial cells (mREC) with leukocytes from diabetic mice resulted in significantly more dead endothelial cells than when leukocytes were isolated from nondiabetic animals. In contrast, diabetes-induced killing of endothelial cells in the co-culture assay was significantly inhibited when using leukocytes isolated from diabetic animals who had been treated daily with PBM as an intervention therapy. N, non-diabetic; D, diabetic; D+PBM, mice getting PBM as an intervention for the last 10 weeks of diabetes. Horizontal lines above the figure indicate significant differences. n = 3 per group.
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pone.0139003.g003: Intervention with PBM mitigates leukocyte-mediated cytotoxicity of endothelial cells caused by leukocytes from diabetic animals.Co-culture of transformed mouse retinal endothelial cells (mREC) with leukocytes from diabetic mice resulted in significantly more dead endothelial cells than when leukocytes were isolated from nondiabetic animals. In contrast, diabetes-induced killing of endothelial cells in the co-culture assay was significantly inhibited when using leukocytes isolated from diabetic animals who had been treated daily with PBM as an intervention therapy. N, non-diabetic; D, diabetic; D+PBM, mice getting PBM as an intervention for the last 10 weeks of diabetes. Horizontal lines above the figure indicate significant differences. n = 3 per group.

Mentions: 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, iNOS (Figs 1 and 2), nor the tests of visual function differed appreciably between the diabetics getting PBM with or without the head shield, suggesting that the beneficial effects of PBM on the retina in diabetes did not require direct illumination of the head or eyes for these parameters. As an additional test of PBM’s systemic effects, we assessed the ability of PBM to exert beneficial effects on leukocytes flowing in the systemic circulation. We previously have found that leukocytes play a major role in diabetes-induced degeneration of retinal capillaries [23,39]. Consistent with our prior reports, leukocytes 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 min per day totally suppressed the diabetes-induced killing of retinal endothelial cells by leukocytes from diabetic mice.


Photobiomodulation Mitigates Diabetes-Induced Retinopathy by Direct and Indirect Mechanisms: Evidence from Intervention Studies in Pigmented Mice.

Saliba A, Du Y, Liu H, Patel S, Roberts R, Berkowitz BA, Kern TS - PLoS ONE (2015)

Intervention with PBM mitigates leukocyte-mediated cytotoxicity of endothelial cells caused by leukocytes from diabetic animals.Co-culture of transformed mouse retinal endothelial cells (mREC) with leukocytes from diabetic mice resulted in significantly more dead endothelial cells than when leukocytes were isolated from nondiabetic animals. In contrast, diabetes-induced killing of endothelial cells in the co-culture assay was significantly inhibited when using leukocytes isolated from diabetic animals who had been treated daily with PBM as an intervention therapy. N, non-diabetic; D, diabetic; D+PBM, mice getting PBM as an intervention for the last 10 weeks of diabetes. Horizontal lines above the figure indicate significant differences. n = 3 per group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591336&req=5

pone.0139003.g003: Intervention with PBM mitigates leukocyte-mediated cytotoxicity of endothelial cells caused by leukocytes from diabetic animals.Co-culture of transformed mouse retinal endothelial cells (mREC) with leukocytes from diabetic mice resulted in significantly more dead endothelial cells than when leukocytes were isolated from nondiabetic animals. In contrast, diabetes-induced killing of endothelial cells in the co-culture assay was significantly inhibited when using leukocytes isolated from diabetic animals who had been treated daily with PBM as an intervention therapy. N, non-diabetic; D, diabetic; D+PBM, mice getting PBM as an intervention for the last 10 weeks of diabetes. Horizontal lines above the figure indicate significant differences. n = 3 per group.
Mentions: 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, iNOS (Figs 1 and 2), nor the tests of visual function differed appreciably between the diabetics getting PBM with or without the head shield, suggesting that the beneficial effects of PBM on the retina in diabetes did not require direct illumination of the head or eyes for these parameters. As an additional test of PBM’s systemic effects, we assessed the ability of PBM to exert beneficial effects on leukocytes flowing in the systemic circulation. We previously have found that leukocytes play a major role in diabetes-induced degeneration of retinal capillaries [23,39]. Consistent with our prior reports, leukocytes 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 min per day totally suppressed the diabetes-induced killing of retinal endothelial cells by leukocytes from diabetic mice.

Bottom Line: 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.SnPP+PBM significantly reduced iNOS expression compared to PBM alone, but significantly exacerbated leukostasis.Beneficial effects on the retina likely are mediated by both direct and indirect mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Case Western Reserve University, Cleveland, Ohio, United States of America; Catholic University of Brasilia, Brasilia, Brazil.

ABSTRACT

Objective: Daily application of far-red light from the onset of diabetes mitigated diabetes-induced abnormalities in 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 diabetes. Direct and indirect effects of PBM on the retina also were studied.

Methods: Diabetes was induced in C57Bl/6J mice using streptozotocin. Some diabetics were exposed to PBM therapy (4 min/day; 670 nm) daily. In 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-1. 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.

Results: PBM intervention 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. SnPP+PBM significantly reduced iNOS expression compared to PBM alone, but significantly exacerbated leukostasis. In study 2, PBM largely mitigated diabetes-induced retinal calcium channel dysfunction in all retinal layers.

Conclusions: PBM induces retinal protection against abnormalities induced by diabetes in pigmented 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.

No MeSH data available.


Related in: MedlinePlus