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

Pinelli, Roberto; Bertelli, Matteo; Scaffidi, Elena; Bumah, V V; Biagioni, Francesca; Busceti, Carla Letizia; Puglisi‐Allegra, Stefano; Fornai, Francesco

doi:10.12871/000398292021343

Cited by 4 publications

(11 citation statements)

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“…In this way, recent evidence accumulates showing that sound stimulates stem cells (Wang et al, 2019) just like we reported for light. Again, as reported by Zeng (2019), such an effect is bound to autophagy activation and modulation of exosome trafficking, which is key in retinal plasticity (Pinelli et al, 2021b). The role of sound in inducing stem cells is wide and occurs in various tissues (Chiang et al, 2019;Zhou et al, 2019).…”

Section: Discussionmentioning

confidence: 80%

“…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%

“…The occurrence of retinal degeneration is postulated to derive from focal subcellular autophagy impairment at various retinal levels (Pinelli et al, 2020c), and it may serves to distinguish between different phenotypes of retinal degeneration (Pinelli et al, 2020c;Kim et al, 2021;Shijo et al, 2021;Wu et al, 2021). In fact, according to the hypothesis of an exosome-dependent trafficking of misfolded proteins towards different poles of the retina, as inferred by pre-clinical studies (Pinelli et al, 2020c;2021a;2021b), various autophagy-mediated pathogenic mechanisms within the retina may be implicated. In detail, the updated retinal microanatomy indicates that RPE as well as Muller cells act as a pivot to grant outer and inner retinal metabolism (Gass, 1972;Ambati and Fowler, 2012;Boulton and Dayhaw-Barker, 2001;Bonilha, 2008;Kozlowski, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…In this way, even focal alterations in the autophagy machinery affecting subcellular domain may play a role in conditioning retinal integrity (Pinelli et al, 2020c). Again, the ability of autophagy to alter the trafficking of exosomes across various retinal layers may explain the progression of autophagy-dependent beneficial or deleterious effects across the whole retina as inferred by pre-clinical studies (Pinelli et al, 2020c;2021a;2021b). Various autophagy-mediated pathogenic mechanisms for retinal degeneration are implicated.…”

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: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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Curcumin as a Perspective Protection for Retinal Pigment Epithelium during Autophagy Inhibition in the Course of Retinal Degeneration

Pinelli

Ferrucci²,

Biagioni

et al. 2023

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Defective autophagy in the retinal pigment epithelium (RPE) is involved in retinal degeneration, mostly in the course of age-related macular degeneration (AMD), which is an increasingly prevalent retinal disorder, eventually leading to blindness. However, most autophagy activators own serious adverse effects when administered systemically. Curcumin is a phytochemical, which induces autophagy with a wide dose-response curve, which brings minimal side effects. Recent studies indicating defective autophagy in AMD were analyzed. Accordingly, in this perspective, we discuss and provide some evidence about the protective effects of curcumin in preventing RPE cell damage induced by the autophagy inhibitor 3-methyladenine (3-MA). Cells from human RPE were administered the autophagy inhibitor 3-MA. The cell damage induced by 3-MA was assessed at light microscopy by hematoxylin & eosin, Fluoro Jade-B, and ZO1 immunohistochemistry along with electron microscopy. The autophagy inhibitor 3-MA produces cell loss and cell degeneration of RPE cells. These effects are counteracted dose-dependently by curcumin. In line with the hypothesis that the autophagy machinery is key in sustaining the integrity of the RPE, here we provide evidence that the powerful autophagy inhibitor 3-MA produces dose-dependently cell loss and cell degeneration in cultured RPE cells, while inhibiting autophagy as shown by LC3-II/LC3-I ratio and gold-standard assessment of autophagy through LC3-positive autophagy vacuoles. These effects are prevented dose-dependently by curcumin, which activates autophagy. These data shed the perspective of validating the role of phytochemicals as safe autophagy activators to treat AMD.

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Autophagy Activation Promoted by Pulses of Light and Phytochemicals Counteracting Oxidative Stress during Age-Related Macular Degeneration

Pinelli¹,

Ferrucci

Biagioni

et al. 2023

Antioxidants

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The seminal role of autophagy during age-related macular degeneration (AMD) lies in the clearance of a number of reactive oxidative species that generate dysfunctional mitochondria. In fact, reactive oxygen species (ROS) in the retina generate misfolded proteins, alter lipids and sugars composition, disrupt DNA integrity, damage cell organelles and produce retinal inclusions while causing AMD. This explains why autophagy in the retinal pigment epithelium (RPE), mostly at the macular level, is essential in AMD and even in baseline conditions to provide a powerful and fast replacement of oxidized molecules and ROS-damaged mitochondria. When autophagy is impaired within RPE, the deleterious effects of ROS, which are produced in excess also during baseline conditions, are no longer counteracted, and retinal degeneration may occur. Within RPE, autophagy can be induced by various stimuli, such as light and naturally occurring phytochemicals. Light and phytochemicals, in turn, may synergize to enhance autophagy. This may explain the beneficial effects of light pulses combined with phytochemicals both in improving retinal structure and visual acuity. The ability of light to activate some phytochemicals may further extend such a synergism during retinal degeneration. In this way, photosensitive natural compounds may produce light-dependent beneficial antioxidant effects in AMD.

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

Cited by 4 publications

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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

Curcumin as a Perspective Protection for Retinal Pigment Epithelium during Autophagy Inhibition in the Course of Retinal Degeneration

Autophagy Activation Promoted by Pulses of Light and Phytochemicals Counteracting Oxidative Stress during Age-Related Macular Degeneration

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