Nutraceuticals for dry age-related macular degeneration: a case report based on novel pathogenic and morphological insights

Pinelli, Roberto; Bertelli, M. S. M.; Scaffidi, Elena; Polzella, Maico; Fulceri, Federica; Biagioni, Francesca; Fornai, Francesco

doi:10.12871/00039829202013

Cited by 9 publications

(9 citation statements)

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“…Among innumerous biochemical cascades, which regulate neuronal integrity in the retina, the autophagy machinery owns a seminal role to maintain cell survival and sustain retinal anatomy including plasticity. This is in line with the involvement of an impaired autophagy in producing a variety of retinal disorders (Pinelli et al, 2020b;2020c;Intartaglia et al, 2021). In its essential definition, autophagy is involved in the clearance of misfolded proteins and damaged mitochondria.…”

Section: Introductionsupporting

confidence: 70%

“…The powerful plastic effects of light are evident already in the retina itself since pioneer papers during the mid'70s up to recent reports. This concept, is well established concerning intrinsic retinal circuitries connected with vision (Berry, 1976;Rose, 1977), and during retinal degeneration (Pinelli et al, 2020a;Pinelli et al, 2021a;2021b;2021c;Strettoi et al, 2022) including plastic changes in the retinal pigment epithelium (Pinelli et al, 2020b). This is now strengthened by evidence showing that specific wavelengths increase proliferation rate of retinal stem cells over four-fold compared with that measured in baseline conditions (Wang et al, 2019).…”

Section: Discussionmentioning

confidence: 88%

“…In fact, stem cell in the CNS are strongly stimulated to proliferate and differentiate towards a neuronal phenotype following autophagy activation (Chang et al, 2020). In recent reports we provided evidence showing that autophagy activation may sort protective effects and promote anatomical and functional recovery in the retina affected by chronic degeneration (Pinelli et al, 2020b(Pinelli et al, , 2020c2020d;2021a;2021b). In fact, the autophagy status of a number of retinal cells is key in promoting the integrity of the retina.…”

Section: Introductionmentioning

confidence: 99%

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

Pinelli¹,

Berti²,

Scaffidi³

et al. 2022

Archives Italiennes De Biologie

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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.

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Section: Introductionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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

Pinelli¹,

Berti²,

Scaffidi³

et al. 2022

Archives Italiennes De Biologie

View full text Add to dashboard Cite

show abstract

“…The powerful plastic effects of light are evident already in the retina itself since pioneer papers during the mid'70s up to recent reports. This concept, is well established concerning intrinsic retinal circuitries dedicated to visual perception (Berry, 1976;Rose, 1977), and during retinal degeneration (Pinelli et al, 2020a;Pinelli et al, 2021a;Strettoi et al, 2022) including plastic changes in the retinal pigment epithelium (Pinelli et al, 2020b). This is now strengthened by evidence showing that, specific wavelengths increase proliferation rate of retinal stem cells over four-fold compared with that measured in baseline conditions (Wang et al, 2019).…”

Section: From the Retina To Extra-geniculate Areasmentioning

confidence: 86%

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

Pinelli¹,

Bucci

Scaffidi³

et al. 2022

Archives Italiennes De Biologie

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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 periaqueductal 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.

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“…However, the exact cause of dry AMD has not been elucidated, which has limited the development of treatments for dry AMD. Compounds that inhibit poly (ADP-ribose) polymerase-1 (PARP1) [6] and certain antioxidants such as lutein, zeaxanthin, and resveratrol [7][8][9] have been proposed for treating dry AMD. Drugs with antioxidant properties, complement cascade inhibitors, neuroprotective agents, visual cycle inhibitors, Medicina 2022, 58, 1129 2 of 11 gene therapy, and cell-based therapies have also been reported as alternative approaches for the prevention and treatment of dry AMD [10].…”

Section: Introductionmentioning

confidence: 99%

NMDA Receptor Antagonists Degrade Lipofuscin via Autophagy in Human Retinal Pigment Epithelial Cells

Lee

Jeong

2022

Medicina

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Background and Objectives: Age-related macular degeneration is a slow-progressing disease in which lipofuscin accumulates in the retina, causing inflammation and apoptosis of retinal pigment epithelial (RPE) cells. This study aimed to identify N-methyl-D-aspartate (NMDA) signaling as a novel mechanism for scavenging N-retinylidene-N-retinylethanolamine (A2E), a component of ocular lipofuscin, in human RPE cells. Materials and Methods: A2E degradation assays were performed in ARPE-19 cells using fluorescently labeled A2E. The autophagic activity in ARPE-19 cells was measured upon blue light (BL) exposure, after A2E treatment. Autophagy flux was determined by measuring LC3-II formation using immunoblotting and confocal microscopy. To determine whether autophagy via the NMDA receptor is involved in A2E clearance, ATG5-deficient cells were used. Results: Ro 25-6981, an NR2B-selective NMDA receptor antagonist, effectively cleared A2E. Ro 25-6981 reduced A2E accumulation in the lysosomes of ARPE-19 cells at sub-cytotoxic concentrations, while increasing the formation of LC3-II and decreasing p62 protein levels in a concentration-dependent manner. The autophagic flux monitored by RFP-GFP-LC3 and bafilomycin A1 assays was significantly increased by Ro 25-6981. A2E clearance by Ro 25-6981 was abolished in ATG5-depleted ARPE-19 cells, suggesting that A2E degradation by Ro 25-6981 was mediated by autophagy. Furthermore, treatment with other NMDA receptor antagonists, CP-101,606 and AZD6765, showed similar effects on autophagy activation and A2E degradation in ARPE-19 cells. In contrast, glutamate, an NMDA receptor agonist, exhibited a contrasting effect, suggesting that both the activation of autophagy and the degradation of A2E by Ro 25-6981 in ARPE-19 cells occur through inhibition of the NMDA receptor pathway. Conclusions: This study demonstrates that NMDA receptor antagonists degrade lipofuscin via autophagy in human RPE cells and suggests that NMDA receptor antagonists could be promising new therapeutics for retinal degenerative diseases.

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Nutraceuticals for dry age-related macular degeneration: a case report based on novel pathogenic and morphological insights

Cited by 9 publications

References 0 publications

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

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

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

NMDA Receptor Antagonists Degrade Lipofuscin via Autophagy in Human Retinal Pigment Epithelial Cells

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