Articles and Abstracts on Diabetic Retinopathy
Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy
Eells JT, Wong-Riley MT, VerHoeve J, Henry M, Buchman EV, Kane MP, Gould LJ, Das R, Jett M, Hodgson BD, Margolis D, Whelan HT.
Photobiomodulation by light in the red to near infrared range (630-1000 nm) using low energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound healing, improve recovery from ischemic injury in the heart and attenuate degeneration in the injured optic nerve. Recent evidence indicates that the therapeutic effects of red to near infrared light result, in part, from intracellular signaling mechanisms triggered by the interaction of NIR light with the mitochondrial photoacceptor molecule cytochrome c oxidase. We have demonstrated that NIR-LED photo-irradiation increases the production of cytochrome oxidase in cultured primary neurons and reverses the reduction of cytochrome oxidase activity produced by metabolic inhibitors. We have also shown that NIR-LED treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. Photobiomodulation improves wound healing in genetically diabetic mice by upregulating genes important in the promotion of wound healing. More recent studies have provided evidence for the therapeutic benefit of NIR-LED treatment in the survival and functional recovery of the retina and optic nerve in vivo after acute injury by the mitochondrial toxin, formic acid generated in the course of methanol intoxication. Gene discovery studies conducted using microarray technology documented a significant upregulation of gene expression in pathways involved in mitochondrial energy production and antioxidant cellular protection. These findings provide a link between the actions of red to near infrared light on mitochondrial oxidative metabolism in vitro and cell injury in vivo. Based on these findings and the strong evidence that mitochondrial dysfunction is involved in the pathogenesis of numerous diseases processes, we propose that NIR-LED photobiomodulation represents an innovative and non-invasive therapeutic approach for the treatment of tissue injury and disease processes in which mitochondrial dysfunction is postulated to play a role including diabetic retinopathy, age-related macular degeneration, Leber's hereditary optic neuropathy and Parkinson's disease.
Subthreshold Laser Therapy for Diabetic Macular Edema: Metabolic and Safety Issues
Vujosevic S, Martini F, Convento E, Longhin E, Kotsafti O, Parrozzani R, Midena E
Purpose: To review the most important metabolic effects and clinical safety data of subthreshold micropulse diode laser (D-MPL) in diabetic macular edema (DME). Methods: Review of the literature about the mechanisms of action and role of D-MPL in DME. Results: The MPL treatment does not damage the retina and is selectively absorbed by the retinal pigment epithelium (RPE). MPL stimulates secretion of different protective cytokines by the RPE. No visible laser spots on the retina were noted on any fundus image modality in different studies, and there were no changes of the outer retina integrity. Mean central retinal sensitivity (RS) increased in subthreshold micropulse diode laser group compared to standard ETDRS photocoagulation group. Conclusions: MPL is a new, promising treatment option in DME, with both infrared and yellow wavelengths using the less aggressive duty cycle (5%) and fixed power parameters. It appears to be safe from morphologic and functional point of view in mild center involving DME.
Clinical Trial Abstracts on Diabetic Retinopathy Research
Low-intensity far-red light inhibits early lesions that contribute to diabetic retinopathy: in vivo and in vitro
Tang J, Du Y, Lee CA, Talahalli R, Eells JT, Kern TS.
Treatment with light in the far-red to near-infrared region of the spectrum (photobiomodulation [PBM]) has beneficial effects in tissue injury. We investigated the therapeutic efficacy of 670-nm PBM in rodent and cultured cell models of diabetic retinopathy.
Studies were conducted in streptozotocin-induced diabetic rats and in cultured retinal cells. Diabetes-induced retinal abnormalities were assessed functionally, biochemically, and histologically in vivo and in vitro.
We observed beneficial effects of PBM on the neural and vascular elements of retina. Daily 670-nm PBM treatment (6 J/cm(2)) resulted in significant inhibition in the diabetes-induced death of retinal ganglion cells, as well as a 50% improvement of the ERG amplitude (photopic b wave responses) (both P < 0.01). To explore the mechanism for these beneficial effects, we examined physiologic and molecular changes related to cell survival, oxidative stress, and inflammation. PBM did not alter cytochrome oxidase activity in the retina or in cultured retinal cells. PBM inhibited diabetes-induced superoxide production and preserved MnSOD expression in vivo. Diabetes significantly increased both leukostasis and expression of ICAM-1, and PBM essentially prevented both of these abnormalities. In cultured retinal cells, 30-mM glucose exposure increased superoxide production, inflammatory biomarker expression, and cell death. PBM inhibited all of these abnormalities.
PBM ameliorated lesions of diabetic retinopathy in vivo and reduced oxidative stress and cell death in vitro. PBM has been documented to have minimal risk. PBM is noninvasive, inexpensive, and easy to administer. We conclude that PBM is a simple adjunct therapy to attenuate the development of diabetic retinopathy.
Large-spot subthreshold infrared laser to treat diabetic macular edema
Squirrell DM, Stewart AW, Joondeph BC, Danesh-Meyer HV, McGhee CN, Donaldson ML.
To evaluate the efficacy of a large-spot subthreshold infrared laser protocol to treat diabetic maculopathy.
In a prospective, fellow eye, controlled case series, all patients had clinically significant diabetic macular edema (DME) treated with a single application of subthreshold infrared (810 nm) laser. If bilateral disease was present, the fellow eye was treated with conventional macular laser. The study was to include 20 patients. Visual acuity and central macular thickness (CMT) measured by optical coherence tomography (OCT) were assessed in the study and fellow eyes at baseline and 6 months, and any changes were compared.
The 11th patient developed a choroidal infarct with subsequent profound loss of vision immediately after treatment. The study was terminated prematurely at this point. For the remaining 10 patients, there was a trend toward improvement in visual acuity in the study eye compared with the fellow eye at the 6-month follow-up (median change: +1.5 letters for study eye vs -6.5 letters for fellow eye; P = 0.08). There was also significant improvement in OCT-measured CMT in the study eye (mean decrease, 117 microm) compared with deterioration in OCT-measured CMT in the fellow eye (mean increase, 24 microm; P = 0.02).
This subthreshold infrared laser protocol led to improvement in OCT-measured CMT and stabilization of vision in most subjects. The current protocol is however unpredictable and should not be used in the treatment of DME without further modification.
Low power laser treatment of the retina ameliorates neovascularisation in a transgenic mouse model of retinal neovascularisation
Yu PK, Cringle SJ, McAllister IL, Yu DY.
This study was designed to determine if low power laser therapy can achieve amelioration of vasoproliferation yet preserve useful vision in the treated area in a transgenic mouse model of retinal neovascularisation. The mice were anaesthetised and the pupils dilated for ERG and fundus fluorescein angiography on postnatal day 32. The left eyes were treated with approximately 85 laser spots (532 nm, 50 ms, 300 microm diameter) at a power level of 20 mW at the cornea. The eyes were examined using ERG and fluorescein angiography, one, four and six weeks later. Flat mounts of FITC-dextran infused retinas, retinal histology and PEDF immunohistochemistry was studied one or six weeks after laser treatment. In untreated eyes the expected course of retinal neovascularisation in this model was observed. However, retinal neovascularisation in the laser treated eye was significantly reduced. The laser parameters chosen produced only mild lesions which took 10-20 s to become visible. ERG responses were comparable between the treated and untreated eyes, and histology showed only partial loss of photoreceptors in the treated eyes. PEDF intensity corresponded inversely with the extent of neovascularisation. Low power panretinal photocoagulation can inhibit retinal neovascularisation and yet preserve partial visual function in this transgenic mouse model of retinal neovascularisation.
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