Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes.

The present manuscript stems from evidence, which indicates that specific wavelength produce an activation of the autophagy pathway in the retina. These effects were recently reported to synergize with the autophagy-inducing properties of specific phytochemicals. The combined administration of photo-modulation and phytochemicals was recently shown to have a strong potential in eliciting the recovery in the course of retinal degeneration and it was suggested as a non-invasive approach named "Lugano protocol" to treat age-related macular degeneration (AMD). Recent translational findings indicate that the protective role of autophagy may extend also to acute neuronal injuries including traumatic neuronal damage. At the same time, very recent investigations indicate that autophagy activation and retinal anatomical recovery may benefit from sound exposure. Therefore, in the present study, the anatomical rescue of a traumatic neuronal loss at macular level was investigated in a patient with idiopathic macular hole by using a combined approach of physical and chemical non-invasive treatments. In detail, light exposure was administered in combination with sound pulses to the affected retina. This treatment was supplemented by phytochemicals known to act as autophagy inducers, which were administered orally for 6 months. This combined administration of light and sound with nutraceuticals reported here as Advanced Lugano's Protocol (ALP) produced a remarkable effect in the anatomical architecture of the retina affected by the macular hole. The anatomical recovery was almost complete at roughly one year after diagnosis and beginning of treatment. The structural healing of the macular hole was concomitant with a strong improvement of visual acuity and the disappearance of metamorphopsia. The present findings are discussed in the light of a synergism shown at neuronal level between light and sound in the presence of phytochemicals to stimulate autophagy and promote proliferation and neuronal differentiation of retinal stem cells.

Noradrenergic substrates sensing light within brainstem reticular formation as targets for light-induced behavioral and cardiovascular plasticity.

The occurrence of pure light exerts a variety of effects in the human body, which span from behavioral alterations, such as light-driven automatic motor activity, cognition and mood to more archaic vegetative functions, which encompass most organs of the body with remarkable effects on the cardiovascular system. Although empirical evidence clearly indicates occurrence of these widespread effects, the anatomical correlates and long-lasting changes within putatively specific neuronal circuitries remain largely unexplored. A specific role is supposed to take place for catecholamine containing neurons in the core of the brainstem reticular formation, which produces a widespread release of noradrenaline in the forebrain while controlling the vegetative nervous system. An indirect as well as a direct (mono-synaptic) retino-brainstem pathway is hypothesized to rise from a subtype of intrinsically photosensitive retinal ganglion cells (iPRGCs), subtype M1, which do stain for Brn3b, and project to the pre-tectal region (including the olivary pre-tectal nucleus). This pathway provides profuse axon collaterals, which spread to the periacqueductal gray and dorsal raphe nuclei. According to this evidence, a retino-reticular monosynaptic system occurs, which powerfully modulate the noradrenergic hub of reticular nuclei in the lateral column of the brainstem reticular formation. These nuclei, which are evidenced in the present study, provide the anatomical basis to induce behavioral and cardiovascular modulation. The occurrence of a highly interconnected network within these nuclei is responsible for light driven plastic effects, which may alter persistently behavior and vegetative functions as the consequence of long-lasting alterations in the environmental light stimulation of the retina. These changes, which occur within the core of an archaic circuitry such as the noradrenaline-containing neurons of the reticular formation, recapitulate, within the CNS, ancestral effects of light-driven changes, which can be detected already within the retina itself at the level of multipotent photic cells.

The potential effects of nutrients and light on autophagy-mediated visual function and clearance of retinal aggregates.

Increasing findings indicate that a dysfunction in the autophagy machinery is common during retinal degeneration. The present article provides evidence showing that an autophagy defect in the outer retinal layers is commonly described at the onset of retinal degeneration. These findings involve a number of structures placed at the border between the inner choroid and the outer retina encompassing the choriocapillaris, the Bruch's membrane, photoreceptors and Mueller cells. At the center of these anatomical substrates are placed cells forming the retinal pigment epithelium (RPE), where autophagy seems to play most of its effects. In fact, a failure of the autophagy flux is mostly severe at the level of RPE. Among various retinal degenerative disorders, age-related macular degeneration (AMD) is mostly affected by a damage to RPE, which can be reproduced by inhibiting the autophagy machinery and it can be counteracted by the activation of the autophagy pathway. In the present manuscript evidence is provided that such a severe impairment of retinal autophagy may be counteracted by administration of a number of phytochemicals, which possess a strong stimulatory activity on autophagy. Likewise, natural light stimulation administered in the form of pulsatile specific wavelengths is capable of inducing autophagy within the retina. This dual approach to stimulate autophagy is further strengthened by the interaction of light with phytochemicals which is shown to activate the chemical properties of these natural molecules in sustaining retinal integrity. The beneficial effects of photo-biomodulation combined with phytochemicals is based on the removal of toxic lipid, sugar and protein species along with the stimulation of mitochondrial turn-over. Additional effects of autophagy stimulation under the combined effects of nutraceuticals and light pulses are discussed concerning stimulation of retinal stem cells which partly correspond to a subpopulation of RPE cells.

The neurobiology of nutraceuticals combined with light exposure, a case report in the course of retinal degeneration.

The present article presents a case report and discusses the neurobiology underlying the potential neuro-repair induced by combined administration of phytochemicals in a patient undergoing photo-bio-modulation (PBM), which improves anatomical and clinical abnormalities in the course of age-related macular degeneration (AMD). After combined treatments the patient with nutraceuticals and PBM had noticeable improvement of retinal tissue with excellent vision for her age and no worsening of corneal guttae, which was present at the time of diagnosis. The present treatment was tailored, based on translational evidence, to improve the autophagy pathway, which is a key determinant in the onset and progression of AMD. In fact, treatment with specific patterns of light exposure combined with specific phytochemicals, may synergize in improving the microanatomy of the retina by restoring its neurobiology. The combination of light exposure, at selective wavelengths, with the effects produced by the intake of specific phytochemicals to treat AMD is reported here as "Lugano Protocol". Such a clinical protocol represents an "in progress" development backed up by translational research. In fact, recent evidence indicates that, specific phytochemicals, when administered in combination may promote anatomical and functional integrity within the retina. These in turn synergize with analogous effects produced by specific wavelengths, when administered at specific time intervals. The synergism between specific light and combined phytochemicals is discussed at molecular level, where recent data indicate how these treatments, when delivered according to specific patterns, may enhance autophagy in the retina. The improvement of retinal morphology and visual acuity, observed in this case report is thoroughly discussed in the light of the key role of autophagy in regulating the integrity of the retinal epithelium. Despite exciting, and consistent with translational evidence, the clinical report of a disease modifying effect during AMD owns the inherent limit of a case report, which requires wide validation in large number of patients. The potential effectiveness of "Lugano protocol" may apply to other types of retinal degenerations, where common alterations in the autophagy pathway do occur. Thus, such a therapeutic approach may extend to a common late stage of retinal trans-synaptic degeneration, where maladaptive plasticity during several types of retinal degenerative disorders eventually converge.

Effects of Khaya grandifoliola on red blood cells and bone mineral content in rats.

The therapeutic efficacy of a crude water extract of Khaya grandifoliola has been established in mice. This study was designed to assess the effect of the extract on the red blood cells and bone for 7 days, 3 weeks and a recovery period of 3 weeks. Daily administration of the extract showed no related adverse effects on the mortality rate, physical appearance or behaviour of the rats. A general pattern of significant (p < 0.5) increases in the red blood cell (RBC) count, PCV, haemoglobin and plasma iron content was shown by groups administered with extract after 7 and 21 days when compared with control rats. There was a general trend of reduction in the bone minerals determined (Ca, P, Mg and Cu) in the extract administered groups. Significant (p < 0.5) decreases were observed at the 500 mg/kg concentration. The bone potassium and iron content was significantly (p < 0.5) increased in rats administered with extract in a dose-dependent manner. There was an observed significant (p < 0.5) decrease in alkaline phosphatase (ALP) activity in the rats administered with the extract when compared with the control animals. During the recovery period, the haematological indices regressed to values which were still significantly (p < 0.5) higher than those of the control values. These results indicate that K. grandifoliola has a positive effect on erythropoeisis, but no significant effect on bone mineral contents at therapeutic doses. At extremely high doses and during prolonged administration, it may have an adverse effect on bone minerals.

Effects of Khaya grandifoliola (Meliaceae) on some biochemical parameters in rats.

The antimalarial activity of the crude water extract of Khaya grandifoliola (Welw) CDC (Meliaceae) stem bark in mice has been reported. The biochemical effects of the crude water extract at doses of 100, 200 and 500 mg/day were examine in plasma, liver, and heart after 7 and 21 days of administration and after a recovery period of 21 days. The extract had a significant hypoglycaemic, hypoproteinaemic and hypocholesterolaemic effect at p < 0.05 when compared to the control rats. Liver protein content and glutathione (GSH) were significantly reduced (p < 0.05) in groups treated with the extract. The concentration of free fatty acids in the plasma was not significantly reduced in groups treated with the extract. A non-significant increase in liver malondialdehyde (MDA) was observed in the extract-administered groups. After the recovery period, the values returned to levels that were not significantly different from those of the control at (p < 0.05) for all the parameters examined.