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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

Preventive PBM treatment corrects diabetes-induced calcium channel dysfunction across the retina.Central (± 0.4–1 mm from the optic nerve head) retinal manganese uptake (as evaluated via 1/T1) profiles of A) dark adapted WT mice (closed black circles, n = 9), untreated diabetic mice (closed green circle, n = 5), and PBM treated diabetic mice (closed magenta circle, n = 5). Data are shown as a function of distance from the retina / non-retina borders, where 0% is the vitreous/retina border and 100% is the retina/choroid border. Regions near borders are not shown because these regions likely include some signal from outside the retina (i.e., partial volume averaging with vitreous or choroid/sclera). Lines above profiles indicate retinal regions with statistically significant differences between indicated groups. A simplified schematic of retina is provided to provide best estimates of MEMRI localization in the retina. The high resolution of our MEMRI images (21.9 μm axial resolution [40]) and the well-defined laminar structure of retina allows us to reasonably label uptake at 24–50% depth as the inner nuclear layer (INL), at 50–68% depth as the outer nuclear layer (ONL), at 68–88% depth as the rod inner segment region (IS), and > 88% as the rod outer segment region (OS).
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pone.0139003.g004: Preventive PBM treatment corrects diabetes-induced calcium channel dysfunction across the retina.Central (± 0.4–1 mm from the optic nerve head) retinal manganese uptake (as evaluated via 1/T1) profiles of A) dark adapted WT mice (closed black circles, n = 9), untreated diabetic mice (closed green circle, n = 5), and PBM treated diabetic mice (closed magenta circle, n = 5). Data are shown as a function of distance from the retina / non-retina borders, where 0% is the vitreous/retina border and 100% is the retina/choroid border. Regions near borders are not shown because these regions likely include some signal from outside the retina (i.e., partial volume averaging with vitreous or choroid/sclera). Lines above profiles indicate retinal regions with statistically significant differences between indicated groups. A simplified schematic of retina is provided to provide best estimates of MEMRI localization in the retina. The high resolution of our MEMRI images (21.9 μm axial resolution [40]) and the well-defined laminar structure of retina allows us to reasonably label uptake at 24–50% depth as the inner nuclear layer (INL), at 50–68% depth as the outer nuclear layer (ONL), at 68–88% depth as the rod inner segment region (IS), and > 88% as the rod outer segment region (OS).

Mentions: As previously reported [21,33], 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.


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)

Preventive PBM treatment corrects diabetes-induced calcium channel dysfunction across the retina.Central (± 0.4–1 mm from the optic nerve head) retinal manganese uptake (as evaluated via 1/T1) profiles of A) dark adapted WT mice (closed black circles, n = 9), untreated diabetic mice (closed green circle, n = 5), and PBM treated diabetic mice (closed magenta circle, n = 5). Data are shown as a function of distance from the retina / non-retina borders, where 0% is the vitreous/retina border and 100% is the retina/choroid border. Regions near borders are not shown because these regions likely include some signal from outside the retina (i.e., partial volume averaging with vitreous or choroid/sclera). Lines above profiles indicate retinal regions with statistically significant differences between indicated groups. A simplified schematic of retina is provided to provide best estimates of MEMRI localization in the retina. The high resolution of our MEMRI images (21.9 μm axial resolution [40]) and the well-defined laminar structure of retina allows us to reasonably label uptake at 24–50% depth as the inner nuclear layer (INL), at 50–68% depth as the outer nuclear layer (ONL), at 68–88% depth as the rod inner segment region (IS), and > 88% as the rod outer segment region (OS).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139003.g004: Preventive PBM treatment corrects diabetes-induced calcium channel dysfunction across the retina.Central (± 0.4–1 mm from the optic nerve head) retinal manganese uptake (as evaluated via 1/T1) profiles of A) dark adapted WT mice (closed black circles, n = 9), untreated diabetic mice (closed green circle, n = 5), and PBM treated diabetic mice (closed magenta circle, n = 5). Data are shown as a function of distance from the retina / non-retina borders, where 0% is the vitreous/retina border and 100% is the retina/choroid border. Regions near borders are not shown because these regions likely include some signal from outside the retina (i.e., partial volume averaging with vitreous or choroid/sclera). Lines above profiles indicate retinal regions with statistically significant differences between indicated groups. A simplified schematic of retina is provided to provide best estimates of MEMRI localization in the retina. The high resolution of our MEMRI images (21.9 μm axial resolution [40]) and the well-defined laminar structure of retina allows us to reasonably label uptake at 24–50% depth as the inner nuclear layer (INL), at 50–68% depth as the outer nuclear layer (ONL), at 68–88% depth as the rod inner segment region (IS), and > 88% as the rod outer segment region (OS).
Mentions: As previously reported [21,33], 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.

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