Abstract
ObjectiveDaily 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.MethodsDiabetes 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.ResultsPBM 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.ConclusionsPBM 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.
Highlights
Diabetes is a major cause of visual impairment, and there is considerable clinical and research interest in diabetic retinopathy
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 PLOS ONE | DOI:10.1371/journal.pone
PBM induces retinal protection against abnormalities induced by diabetes in pigmented animals, and even as an intervention
Summary
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 involvement by health-care professionals, and not all patients respond to these approaches. Medical PBM using coherent (lasers) or noncoherent (Light Emitting Diodes; LEDs) light has been found to have beneficial effects in a variety of conditions, including accelerated healing of wounds and ulcers, cardiac ischemia, stroke, Parkinson’s disease, and optic nerve degeneration [1,2,3,4,5,6,7,8,9,10,11,12]. Our previous study in diabetic albino rats showed that wholebody exposure to far-red light (670 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]
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