Photobiomodulation Inhibits Long-term Structural and Functional Lesions of Diabetic Retinopathy.

Previous studies demonstrated that brief (3 to 4 min) daily application of light at 670 nm to diabetic rodents inhibited molecular and pathophysiologic processes implicated in the pathogenesis of diabetic retinopathy (DR) and reversed diabetic macular edema in small numbers of patients studied. Whether or not this therapy would inhibit the neural and vascular lesions that characterize the early stages of the retinopathy was unknown. We administered photobiomodulation (PBM) therapy daily for 8 months to streptozotocin-diabetic mice and assessed effects of PBM on visual function, retinal capillary permeability, and capillary degeneration using published methods. Vitamin D receptor and Cyp24a1 transcripts were quantified by quantitative real-time PCR, and the abundance of c-Kit+ stem cells in blood and retina were assessed. Long-term daily administration of PBM significantly inhibited the diabetes-induced leakage and degeneration of retinal capillaries and also significantly inhibited the diabetes-induced reduction in visual function. PBM also inhibited diabetes-induced reductions in retinal Cyp24a1 mRNA levels and numbers of circulating stem cells (CD45-/c-Kit+), but these effects may not account for the beneficial effects of PBM on the retinopathy. PBM significantly inhibits the functional and histopathologic features of early DR, and these effects likely are mediated via multiple mechanisms.

670nm photobiomodulation as a novel protection against retinopathy of prematurity: evidence from oxygen induced retinopathy models.

INTRODUCTION: To investigate the validity of using 670nm red light as a preventative treatment for Retinopathy of Prematurity in two animal models of oxygen-induced retinopathy (OIR). MATERIALS AND METHODS: During and post exposure to hyperoxia, C57BL/6J mice or Sprague-Dawley rats were exposed to 670 nm light for 3 minutes a day (9J/cm²). Whole mounted retinas were investigated for evidence of vascular abnormalities, while sections of neural retina were used to quantify levels of cell death using the TUNEL technique. Organs were removed, weighed and independent histopathology examination performed. RESULTS: 670 nm light reduced neovascularisation, vaso-obliteration and abnormal peripheral branching patterns of retinal vessels in OIR. The neural retina was also protected against OIR by 670 nm light exposure. OIR-exposed animals had severe lung pathology, including haemorrhage and oedema, that was significantly reduced in 670 nm+OIR light-exposed animals. There were no significance differences in the organ weights of animals in the 670 nm light-exposed animals, and no adverse effects of exposure to 670 nm light were detected. DISCUSSION: Low levels of exposure to 670 nm light protects against OIR and lung damage associated with exposure to high levels of oxygen, and may prove to be a non-invasive and inexpensive preventative treatment for ROP and chronic lung disease associated with prematurity.

Low power laser treatment of the retina ameliorates neovascularisation in a transgenic mouse model of retinal neovascularisation.

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.

Retinal vascular changes associated with transpupillary thermotherapy for choroidal melanomas.

PURPOSE: To define retinal vascular changes after transpupillary thermotherapy (TTT) for choroidal melanomas and assess their clinical impact. METHODS: Stereoscopic fluorescein angiogram pairs of 29 patients pre- and post-treatment with TTT were examined for patterns of vascular damage, and the patients were studied for ensuing complications. RESULTS: Widespread retinal capillary loss was confined within the treatment margins except in cases of coexisting large retinal artery or vein occlusions. Artery occlusions occurred in 83%, involving a large artery in 23%. Venous occlusions occurred in 69%, involving large veins in 10%. Subretinal choroidal neovascularization occurred in four cases, in one causing hemorrhage that broke through into the vitreous. No retinal neovascularization occurred. Choroidal vasculature was relatively preserved at the periphery of the treated area. Foveal vascular damage caused visual loss in six cases. Vascular changes beyond the treatment margins did not affect the fovea in any case. Retinal fibrosis affected two cases. Diabetic patients fared no worse than healthy counterparts. CONCLUSIONS: Transpupillary thermotherapy produces characteristic retinal vascular changes that may reduce vision when affecting the fovea. Vascular changes are confined within the treatment margins except in cases of associated large vessel occlusion. There is a small risk of neovascularization, both retinal and choroidal.

Effect of different phototherapy lights on retinal and choroidal blood flow.

The response of retinal (RBF) and choroidal (ChBF) blood flow to illumination with light with different spectra was investigated in spontaneously breathing newborn piglets. After 1 h in complete darkness, the animals were exposed to blue, white or green light in such a manner that equal energy was delivered to the eye. RBF and ChBF showed different flow responses. After 60 min exposure to blue light, RBF increased from 0.22 +/- 0.01 ml/min/g at baseline to 0.32 +/- 0.03 ml/min/g (+/- SEM) (p less than 0.03). Apart from this increase, RBF did not change significantly during any of the experimental settings. ChBF, on the other hand, was significantly affected by illumination. Thus, at 120 min of light exposure all three types of light decreased ChBF significantly from baseline (darkness) levels. Blue light decreased ChBF (mean +/- SEM) from 13.78 +/- 0.84 to 7.61 +/- 0.67 ml/min/g (p less than 0.01), white light from 17.43 +/- 1.86 to 9.86 +/- 1.07 ml/min/g (p less than 0.01), and green light from 14.13 +/- 1.64 to 8.31 +/- 1.30 ml/min/g (p less than 0.02). The results indicate that light is an important modulator of ChBF and to a certain extent also RBF. Further, the results suggest that ChBF and RBF are regulated differently.

Effect of light on oxygen-induced retinopathy in the rat model. Light and OIR in the rat.

The purpose of this study was to establish whether exposure to intense lighting favors the development or aggravates experimental oxygen-induced retinopathy in the newborn rat. Five groups of Wistar rats were studied. The control group was maintained for the first 14 days of life under conditions of cyclical (12L:12D) lighting at 12 Lx in room air. Two other groups were subjected, for the same amount of time, to semi-darkness (2 Lx; 12L: 12D), one with room air and the other with supplemental 80% oxygen. The final two groups were exposed to the same room air and hyperoxic treatments under intense lighting conditions (600 Lx; 12L:12D). After the treatment period, four rats were randomly chosen from each group, sacrificed and their retinas examined under electron microscope. Marked structural changes were seen only in the photoreceptor outer segments of those rats exposed to intense light. In eighty-five of the remaining rats retinal vascular morphology was examined in retinal flat mounts after intracardiac injection of India ink. Retinopathy was observed in rats treated with hyperoxia but no significant differences could be attributed to the light conditions under which the retinopathic rats had been maintained. In the rest of the rats, axonal transport along the optical pathways was evaluated after intravitreal injection of (3H) taurine. In the two groups exposed to hyperoxia, axonal transport was altered, but less markedly in those exposed to intense lighting than in those exposed to semi-darkness. Intense illumination under conditions of normoxia favors axonal transport. Exposure to intense lighting does not seem to aggravate oxygen induced retinopathy in the rat though it does produce structural lesions of the photoreceptors.