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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

Effect of PBM intervention on retinal (a) ICAM-1, (b) iNOS and (c) HO-1 in diabetic mice.Intervention with PBM significantly reversed the diabetes-induced induction of retinal ICAM-1, whereas effects on iNOS and HO-1 expression were less marked or absent. Use of the head shield (PBM + HS) or inhibiting HO-1 with SnPP (PBM + SnPP) did not affect the effect of PBM on expression of ICAM-1 significantly, but SnPP did tend to normalize iNOS expression, and both the head shield and SNPP increased HO-1 expression. Representative immunoblots are shown in (c). Total duration of diabetes was 14 weeks, but PBM was applied only for the last 10 weeks of that duration. N, non-diabetic; D, diabetic; D+PBM, mice getting PBM. Horizontal lines above the figure indicate significant differences. n = 4–6 per group.
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pone.0139003.g002: Effect of PBM intervention on retinal (a) ICAM-1, (b) iNOS and (c) HO-1 in diabetic mice.Intervention with PBM significantly reversed the diabetes-induced induction of retinal ICAM-1, whereas effects on iNOS and HO-1 expression were less marked or absent. Use of the head shield (PBM + HS) or inhibiting HO-1 with SnPP (PBM + SnPP) did not affect the effect of PBM on expression of ICAM-1 significantly, but SnPP did tend to normalize iNOS expression, and both the head shield and SNPP increased HO-1 expression. Representative immunoblots are shown in (c). Total duration of diabetes was 14 weeks, but PBM was applied only for the last 10 weeks of that duration. N, non-diabetic; D, diabetic; D+PBM, mice getting PBM. Horizontal lines above the figure indicate significant differences. n = 4–6 per group.

Mentions: In wildtype C57Bl/6J mice, diabetes caused metabolic and physiologic abnormalities in the retina, including increased superoxide production, leukostasis (Fig 1), increased expression of ICAM-1 and iNOS, and subnormal expression of HO-1 (Fig 2). Diabetes of 2 months duration also significantly impaired visual function, as assessed from spatial frequency threshold and contrast sensitivity (measured at a single point; 0.064 c/d) (not shown; both p<0.0001). Although initiation of the PBM therapy in these pigmented animals was delayed for 1 month of untreated diabetes, the subsequent intervention with PBM therapy nevertheless significantly mitigated many of these defects. Intervention with daily exposure to the PBM totally inhibited the increase in retinal superoxide, and significantly inhibited diabetes-induced abnormalities in leukostasis, retinal ICAM-1 expression, and spatial frequency threshold (p<0.0001). The light therapy had no significant effect on the diabetes-induced changes in retinal iNOS or HO-1 or defect in contrast sensitivity measured in these samples.


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)

Effect of PBM intervention on retinal (a) ICAM-1, (b) iNOS and (c) HO-1 in diabetic mice.Intervention with PBM significantly reversed the diabetes-induced induction of retinal ICAM-1, whereas effects on iNOS and HO-1 expression were less marked or absent. Use of the head shield (PBM + HS) or inhibiting HO-1 with SnPP (PBM + SnPP) did not affect the effect of PBM on expression of ICAM-1 significantly, but SnPP did tend to normalize iNOS expression, and both the head shield and SNPP increased HO-1 expression. Representative immunoblots are shown in (c). Total duration of diabetes was 14 weeks, but PBM was applied only for the last 10 weeks of that duration. N, non-diabetic; D, diabetic; D+PBM, mice getting PBM. Horizontal lines above the figure indicate significant differences. n = 4–6 per group.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139003.g002: Effect of PBM intervention on retinal (a) ICAM-1, (b) iNOS and (c) HO-1 in diabetic mice.Intervention with PBM significantly reversed the diabetes-induced induction of retinal ICAM-1, whereas effects on iNOS and HO-1 expression were less marked or absent. Use of the head shield (PBM + HS) or inhibiting HO-1 with SnPP (PBM + SnPP) did not affect the effect of PBM on expression of ICAM-1 significantly, but SnPP did tend to normalize iNOS expression, and both the head shield and SNPP increased HO-1 expression. Representative immunoblots are shown in (c). Total duration of diabetes was 14 weeks, but PBM was applied only for the last 10 weeks of that duration. N, non-diabetic; D, diabetic; D+PBM, mice getting PBM. Horizontal lines above the figure indicate significant differences. n = 4–6 per group.
Mentions: In wildtype C57Bl/6J mice, diabetes caused metabolic and physiologic abnormalities in the retina, including increased superoxide production, leukostasis (Fig 1), increased expression of ICAM-1 and iNOS, and subnormal expression of HO-1 (Fig 2). Diabetes of 2 months duration also significantly impaired visual function, as assessed from spatial frequency threshold and contrast sensitivity (measured at a single point; 0.064 c/d) (not shown; both p<0.0001). Although initiation of the PBM therapy in these pigmented animals was delayed for 1 month of untreated diabetes, the subsequent intervention with PBM therapy nevertheless significantly mitigated many of these defects. Intervention with daily exposure to the PBM totally inhibited the increase in retinal superoxide, and significantly inhibited diabetes-induced abnormalities in leukostasis, retinal ICAM-1 expression, and spatial frequency threshold (p<0.0001). The light therapy had no significant effect on the diabetes-induced changes in retinal iNOS or HO-1 or defect in contrast sensitivity measured in these samples.

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