Photobiomodulation preserves mitochondrial redox state and is retinoprotective in a rodent model of retinitis pigmentosa.

Photobiomodulation (PBM) by far-red (FR) to near-infrared (NIR) light has been demonstrated to restore the function of damaged mitochondria, increase the production of cytoprotective factors and prevent cell death. Our laboratory has shown that FR PBM improves functional and structural outcomes in animal models of retinal injury and retinal degenerative disease. The current study tested the hypothesis that a brief course of NIR (830 nm) PBM would preserve mitochondrial metabolic state and attenuate photoreceptor loss in a model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated with 830 nm light (180 s; 25 mW/cm2; 4.5 J/cm2) using a light-emitting diode array (Quantum Devices, Barneveld, WI) from postnatal day (p) 10 to p25. Sham-treated rats were restrained, but not treated with 830 nm light. Retinal metabolic state, function and morphology were assessed at p30 by measurement of mitochondrial redox (NADH/FAD) state by 3D optical cryo-imaging, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), and histomorphometry. PBM preserved retinal metabolic state, retinal function, and retinal morphology in PBM-treated animals compared to the sham-treated group. PBM protected against the disruption of the oxidation state of the mitochondrial respiratory chain observed in sham-treated animals. Scotopic ERG responses over a range of flash intensities were significantly greater in PBM-treated rats compared to sham controls. SD-OCT studies and histological assessment showed that PBM preserved the structural integrity of the retina. These findings demonstrate for the first time a direct effect of NIR PBM on retinal mitochondrial redox status in a well-established model of retinal disease. They show that chronic proteotoxic stress disrupts retinal bioenergetics resulting in mitochondrial dysfunction, and retinal degeneration and that therapies normalizing mitochondrial metabolism have considerable potential for the treatment of retinal degenerative disease.

Photobiomodulation with 670 nm light ameliorates Müller cell-mediated activation of microglia and macrophages in retinal degeneration.

Müller cells, the supporting cells of the retina, play a key role in responding to retinal stress by releasing chemokines, including CCL2, to recruit microglia and macrophages (MG/MΦ) into the damaged retina. Photobiomodulation (PBM) with 670 nm light has been shown to reduce inflammation in models of retinal degeneration. In this study, we aimed to investigate whether 670 nm light had an effect on Müller cell-initiated inflammation under retinal photo-oxidative damage (PD) in vivo and in vitro. Sprague-Dawley rats were pre-treated with 670 nm light (9J/cm2) once daily over 5 days prior to PD. The expression of inflammatory genes including CCL2 and IL-1ß was analysed in retinas. In vitro, primary Müller cells dissociated from neonatal rat retinas were co-cultured with 661W photoreceptor cells. Co-cultures were exposed to PD, followed by 670 nm light treatment to the Müller cells only, and Müller cell stress and inflammation were assessed. Primary MG/MΦ were incubated with supernatant from the co-cultures, and collected for analysis of inflammatory activation. To further understand the mechanism of 670 nm light, the expression of COX5a and mitochondrial membrane potential (ΔΨm) were measured in Müller cells. Following PD, 670 nm light-treated Müller cells had a reduced inflammatory activation, with lower levels of CCL2, IL-1ß and IL-6. Supernatant from 670 nm light-treated co-cultures reduced activation of primary MG/MΦ, and lowered the expression of pro-inflammatory cytokines, compared to untreated PD controls. Additionally, 670 nm light-treated Müller cells had an increased expression of COX5a and an elevated ΔΨm following PD, suggesting that retrograde signaling plays a role in the effects of 670 nm light on Müller cell gene expression. Our data indicates that 670 nm light reduces Müller cell-mediated retinal inflammation, and offers a potential cellular mechanism for 670 nm light therapy in regulating inflammation associated with retinal degenerations.

Differential effects of 670 and 830 nm red near infrared irradiation therapy: a comparative study of optic nerve injury, retinal degeneration, traumatic brain and spinal cord injury.

Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P ≤ 0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P ≤ 0.05) in this model. Pre-treatment of light-induced retinal degeneration with 670 nm R/NIR-IT significantly reduced the number of Tunel+ cells and 8-hydroxyguanosine immunoreactivity (P ≤ 0.05); outcomes in 830 nm R/NIR-IT treated animals were not significantly different to controls. Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R/NIR-IT individually for different CNS injury types.

Visual complications of Stickler syndrome in paediatric patients with Robin sequence.

BACKGROUND: The most frequent diagnosis in patients with syndromic Pierre Robin sequence is Stickler syndrome, which may be complicated by congenital high myopia and substantial risk of retinal detachment. However, cases of Stickler syndrome with probable visual complications are rarely identified among this group of patients by members of the cleft team. This study was designed to determine the prevalence of Stickler syndrome among the author's group of patients with Robin sequence, and to investigate the visual outcome among paediatric patients with Robin sequence and Stickler syndrome. MATERIAL AND METHODS: Eight children (six male and two female) with Stickler syndrome and Robin sequence were referred to be followed up every 6 months in the Ophthalmologic Department because of high myopia at less than 10 years of age. Three patients came from the author's study group and five were referred by other cleft surgeons. They were examined with repeat ophthalmic and indirect fundus examinations including cycloplegic refraction, and slit lamp biomicroscope examinations. Laser photocoagulation (2 cases) treatment for retinal degeneration or operation (3 cases) for retinal detachment was performed once evidence of significant ophthalmologic finding was noted. RESULTS: Of the 91 cases of newborns with isolated cleft palate treated by the first author, eight patients had Robin sequence, and among these, three had Stickler syndrome. The prevalence of Stickler syndrome among this subgroup of patients was 37.5% (3/8). Among these three patients and the additional five referred by other cleft surgeons, the average spherical equivalents of the first cycloplegic refraction for the 16 eyes was -12.39+/-2.72 diopter (D) (range -8.75 to -18.5D). Of the eight patients, five did not need any therapy, two children had retinal degeneration in the left eye and retinal detachment in the right eye while one child had retinal detachment in the right eye only. Laser photocoagulation was performed in the two left eyes with retinal degeneration and was successful. Surgery was performed on the three eyes with retinal detachment, one was successful while two failed and the patients developed total blindness at ages four and six respectively. Out of these three children with retinal complications, only one child remained free of visual deterioration in both eyes during the follow-up period. CONCLUSION: Early identification of Stickler syndrome in children with Robin sequence by cleft surgeons is necessary to insure early referral to an ophthalmologist for detection of myopia, monitoring for retinal detachment, and prevention of visual complications.

[Dependence of the efficiency of low-intensity laser therapy in involution chorioretinal dystrophy on a used wavelength]. / Zavisimost' effektivnosti nizkointensivnoi lazernoi terapii involiutsionnoi tsentral'noi khorioretinal'noi distrofii ot primeniaemoi dliny volny.

Seventy-five patients (75 eyes) with central involution chorioretinal dystrophy (non-exudative type at the progression stage) were followed up. All of them received low-intensity laser therapy. Irradiation of 890 nm, 644 nm and 500 nm was used in groups 1, 2 and 3, respectively. The study purpose was to compare the efficiency of wavelengths. Visual acuity and retinal sensitivity were determined. The results were evaluated immediately after treatment and in 3 months. The maximal improvement in visual acuity and retinal sensitivity was in those who received 890 nm laser therapy; 500 nm irradiation--a less pronounced effect and 640 nm--the lowest one. We attribute such distribution of efficiency to a proliferation type of each irradiation range in the macular zone.

[The mechanism of action of laser stimulation of the eye]. / K mekhanizmu deistviia lazerstimuliatsii organa zreniia.

The mechanism of action of helium-neon laser stimulation has been studied in 26 eyes of 15 patients with dystrophic diseases of the eye and on the ground of 63 lymphangiographic investigations of the same patients. It was found that low-energy helium-neon laser stimulation (0.05-0.5 mWt/cm2) has a positive effect on restoration of visual functions. Lymphangiographic investigations have revealed a new biological phenomenon--activation of disturbed lymphatic flow under the action of a specially organized laser radiation. The results obtained confirm the earlier hypothesis (M. M. Krasnov et al., 1982) that under the action of laser radiation a normal physiologic system purifying the retina from disintegrated products is engaged into action.

Preservation of retinal function in the RCS rat by laser treatment.

The Royal College of Surgeons (RCS) rats have been used as a model for human retinitis pigmentosa. Studies on these animals have shown that the degeneration of the retina is associated with a buildup of debris produced by shed rod outer segment discs. It has been reported that localized laser lesions can increase phagocytosis in these rats. This study examined the effect of laser burns on the function of the retina of the RCS rats. One eye of 19-day-old RCS rats was treated with laser and the other eye used as control. The retinal function was measured by electroretinography at 5, 10, 15, 20, 25, 30, and 40 days after lesioning. The morphology of the retina was examined at 24 and 43 days after laser treatment. The results show that the retinal function in the treated eye was improved at all intervals and that this improvement was significant at 15, 20, and 25 days. Morphologic examination showed a significant reduction in debris accumulation in the area of the laser spot. However, at sites distal to the laser burns, no morphologic difference between the treated and untreated eyes was noted. It is concluded that the progress of retinal dysfunction in the RCS rats can be retarded by laser treatment.