Retinal Degeneration Following Chronic Administration of the Parkinsonism-Inducing Neurotoxin MPTP

Pinelli, Roberto; Biagioni, Francesca; Bertelli, Matteo; Busceti, Carla Letizia; Scaffidi, Elena; Ryskalin, Larisa; Fornai, Francesco

doi:10.12871/00039829202122

Cited by 4 publications

(8 citation statements)

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“…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%

“…We recently probed a treatment based on translational evidence, which combines physical and chemical remedies, such as light exposure and nutraceuticals, according to what it was defined as "Lugano's protocol" (Pinelli et al, 2020c), which was hypothesized to converge in upregulating the autophagy status within the retina. This approach produced a remarkable regression of anatomical and visual impairment in a case of a degenerative retinal disorder (Pinelli et al, 2021c). In detail, in search for a potential synergism in inducing autophagy within the retina, a combined therapeutic approach was tempted in which nutraceuticals were administered, following pulses of different light owing different wavelengths.…”

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: 88%

Section: Introductionmentioning

confidence: 99%

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

“…Looping is also associated with defective optic nerve projection which leads to visual system impairment [ 45 ]. Evidently, MPTP administration was found to cause retinal degeneration, a vital component that communicates with the optic nerve [ 17 ]. Apoptotic photoreceptors and inner retina neuronal loss were observed in mice treated with MPTP [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Evidently, MPTP administration was found to cause retinal degeneration, a vital component that communicates with the optic nerve [ 17 ]. Apoptotic photoreceptors and inner retina neuronal loss were observed in mice treated with MPTP [ 17 ]. The optokinetic response (OKR) assay, which uses alternating dark and light concept, is particularly useful for assessing zebrafish visual-motor response and visual acuity [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

“…The diminished nigral dopaminergic neurons in the MPTP-induced zebrafish model has been reported to cause movement abnormalities that mimic PD-like dyskinesia and bradykinesia [ 5 , 14 ]. Besides, studies have also reported on weakened olfactory [ 15 ], tactile senses [ 16 ], and visual impairments [ 17 ] in PD animal models upon MPTP induction.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of neurobehavioral pattern in a zebrafish 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model: A 96-hour behavioral study

et al. 2022

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Parkinson’s disease (PD) is the most common brain motor disorder, characterized by a substantial loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Motor impairments, such as dyskinesia, bradykinesia, and resting tremors, are the hallmarks of PD. Despite ongoing research, the exact PD pathogenesis remains elusive due to the disease intricacy and difficulty in conducting human studies. Zebrafish (Danio rerio) has emerged as an ideal model for researching PD pathophysiology. Even though 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been used to induce PD in zebrafish, behavioural findings are frequently limited to a single time point (24 hours post-injection). In this sense, we aim to demonstrate the effects of MPTP on zebrafish swimming behaviour at multiple time points. We administered a single dosage of MPTP (200μg/g bw) via intraperitoneal injection (i/p) and assessed the locomotor activity and swimming pattern at 0h, 24h, and 96h post-injection through an open field test. Analysis of the behaviour revealed significant reductions in swimming velocity (cm/s) and distance travelled (cm), concurrent with an increase in freezing maintenance (duration and bouts) in zebrafish injected with MPTP. In addition, the MPTP-injected zebrafish exhibited complex swimming patterns, as measured by the turn angle, meander, and angular velocity, and showed abnormal swimming phenotypes, including freezing, looping, and erratic movement. To conclude, MPTP administration into adult zebrafish induced hypolocomotion and elicited motor incoordination. Plus, the effects of MPTP were observable 24 hours after the injection and still detectable 96 hours later. These findings contribute to the understanding of MPTP effects on adult zebrafish, particularly in terms of swimming behaviours, and may pave the way for a better understanding of the establishment of PD animal models in the future.

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Intravitreal MPTP drives retinal ganglion cell loss with oral nicotinamide treatment providing robust neuroprotection

Rombaut,

Jovancevic,

Wong

et al. 2024

acta neuropathol commun

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Neurodegenerative diseases have common underlying pathological mechanisms including progressive neuronal dysfunction, axonal and dendritic retraction, and mitochondrial dysfunction resulting in neuronal death. The retina is often affected in common neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. Studies have demonstrated that the retina in patients with Parkinson’s disease undergoes changes that parallel the dysfunction in the brain. These changes classically include decreased levels of dopamine, accumulation of alpha-synuclein in the brain and retina, and death of dopaminergic nigral neurons and retinal amacrine cells leading to gross neuronal loss. Exploring this disease's retinal phenotype and vision-related symptoms is an important window for elucidating its pathophysiology and progression, and identifying novel ways to diagnose and treat Parkinson’s disease. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is commonly used to model Parkinson’s disease in animal models. MPTP is a neurotoxin converted to its toxic form by astrocytes, transported to neurons through the dopamine transporter, where it causes mitochondrial Complex I inhibition and neuron degeneration. Systemic administration of MPTP induces retinal changes in different animal models. In this study, we assessed the effects of MPTP on the retina directly via intravitreal injection in mice (5 mg/mL and 50 mg/mL to 7, 14 and 21 days post-injection). MPTP treatment induced the reduction of retinal ganglion cells—a sensitive neuron in the retina—at all time points investigated. This occurred without a concomitant loss of dopaminergic amacrine cells or neuroinflammation at any of the time points or concentrations tested. The observed neurodegeneration which initially affected retinal ganglion cells indicated that this method of MPTP administration could yield a fast and straightforward model of retinal ganglion cell neurodegeneration. To assess whether this model could be amenable to neuroprotection, mice were treated orally with nicotinamide (a nicotinamide adenine dinucleotide precursor) which has been demonstrated to be neuroprotective in several retinal ganglion cell injury models. Nicotinamide was strongly protective following intravitreal MPTP administration, further supporting intravitreal MPTP use as a model of retinal ganglion cell injury. As such, this model could be utilized for testing neuroprotective treatments in the context of Parkinson’s disease and retinal ganglion cell injury.

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Retinal Degeneration Following Chronic Administration of the Parkinsonism-Inducing Neurotoxin MPTP

Cited by 4 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

Characterization of neurobehavioral pattern in a zebrafish 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model: A 96-hour behavioral study

Intravitreal MPTP drives retinal ganglion cell loss with oral nicotinamide treatment providing robust neuroprotection

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