Retinal Plasticity

Strettoi, Enrica; Marco, Beatrice Di; Orsini, Noemi; Napoli, Debora

doi:10.3390/ijms23031138

Cited by 10 publications

(5 citation statements)

References 83 publications

(86 reference 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%

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%

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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“…It results from the death of photoreceptors leading to significant visual impairment and ultimately, blindness. A large body of evidence shows that the impact of RP continues to the inner retina which undergoes change secondary to photoreceptor loss ( Jones et al, 2003 ; Marc et al, 2003 ; Strettoi et al, 2003 ; Jones and Marc, 2005 ; Marc et al, 2007 ; Chua et al, 2009 , 2013 ; Kalloniatis et al, 2013 ; Greferath et al, 2015 ; Pfeiffer et al, 2020b ; Strettoi et al, 2022 ). These changes are complex, and include anatomical, metabolic and functional alterations of both neurons and glia in the inner retina ( Jones et al, 2003 ; Marc et al, 2003 ; Strettoi et al, 2003 ; Jones and Marc, 2005 ; Marc et al, 2007 ; Chua et al, 2009 , 2013 ; Kalloniatis et al, 2013 ; Greferath et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Loss of Müller cell glutamine synthetase immunoreactivity is associated with neuronal changes in late-stage retinal degeneration

Reynisson

Kalloniatis²,

Fletcher³

et al. 2023

Front. Neuroanat.

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IntroductionA hallmark of photoreceptor degenerations is progressive, aberrant remodeling of the surviving retinal neurons and glia following photoreceptor loss. The exact relationship between neurons and glia remodeling in this late stage of retinal degeneration, however, is unclear. This study assessed this by examining Müller cell dysfunction via glutamine synthetase immunoreactivity and its spatial association with retinal neuron subpopulations through various cell markers.MethodsAged Rd1 mice retinae (P150 – P536, n = minimum 5 per age) and control heterozygous rd1 mice retinae (P536, n = 5) were isolated, fixed and cryosectioned. Fluorescent immunolabeling of glutamine synthetase was performed and retinal areas quantified as having low glutamine synthetase immunoreactivity if proportion of labeled pixels in an area was less than two standard deviations of the mean of the total retina. Other Müller cell markers such as Sox9 and Glial fibrillary acidic protein along with neuronal cell markers Calbindin, Calretinin, recoverin, Protein kinase C-α, Glutamic acid decarboxylase 67, and Islet-1 were then quantified within areas of low and normal synthetase immunoreactivity.ResultsGlutamine synthetase immunoreactivity was lost as a function of age in the rd1 mouse retina (P150 – P536). Immunoreactivity of other Müller cell markers, however, were unaffected suggesting Müller cells were still present in these low glutamine synthetase immunoreactive regions. Glutamine synthetase immunoreactivity loss affected specific neuronal populations: Type 2, Type 8 cone, and rod bipolar cells, as well as AII amacrine cells based on reduced recoverin, protein kinase Ca and parvalbumin immunoreactivity, respectively. The number of cell nuclei within regions of low glutamine synthetase immunoreactivity was also reduced suggesting possible neuronal loss rather than reduced cell marker immunoreactivity.ConclusionThese findings further support a strong interplay between glia-neuronal alterations in late-stage degeneration and highlight a need for future studies and consideration in intervention development.

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“…Consequences of total or near total loss of outer retinal photoreceptors, rods and cones, to the inner retina function have been widely studied using animal models of retinal degenerative diseases ( D’Orazi et al, 2014 ; Strettoi, 2015 ; Pfeiffer et al, 2020 ; Strettoi et al, 2022 ). With respect to clinical correlates, corresponding anatomic data have been obtained from patient retinas postmortem ( Jones et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Visual System Hyperexcitability and Compromised V1 Receptive Field Properties in Early-Stage Retinitis Pigmentosa in Mice

Leinonen

Lyon²,

Palczewski³

et al. 2022

eNeuro

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Inherited retinal degenerative diseases are a prominent cause of blindness. Although mutations causing death of photoreceptors are mostly known, the pathophysiology downstream in the inner retina and along the visual pathway is incompletely characterized in the earliest disease stages. Here, we investigated retinal, midbrain and cortical visual function using electroretinography (ERG), the optomotor response (OMR), visual evoked potentials (VEPs), respectively, and single unit electrophysiology at the primary visual cortex (V1) in light-adapted juvenile (approximately one-month-old) and young adult (three-month-old) Rho P23H/WT mice, representative of early-stage retinitis pigmentosa (RP). Photopic ERG revealed up to ∼30% hypersensitivity to light in Rho P23H/WT mice, as measured by the light intensity required to generate half-maximal b-wave (I 50 parameter). Rho P23H/WT mice also showed increased OMRs toward low spatial frequency (SF) drifting gratings, indicative of visual overexcitation at the midbrain level. At the V1 level, VEPs and single-cell recordings revealed prominent hyperexcitability in the juvenile Rho P23H/WT mice. Mean VEP amplitudes for light ON stimuli were nearly doubled in one-month-old Rho P23H/WT mice compared with controls, and more than doubled for light OFF. Single-cell recordings showed a significantly increased spontaneous V1 neuron firing in the Rho P23H/WT mice, and persistent contrast and temporal sensitivities. In contrast, direction selectivity was severely compromised. Our data suggest that during early RP, the visual pathway becomes hyperexcited. This could have both compensatory and deleterious consequences for visual behavior. Further studies on the mechanisms of hyperexcitability are warranted as this could lead to therapeutic interventions for RP.

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Retinal Plasticity

Cited by 10 publications

References 83 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

Loss of Müller cell glutamine synthetase immunoreactivity is associated with neuronal changes in late-stage retinal degeneration

Visual System Hyperexcitability and Compromised V1 Receptive Field Properties in Early-Stage Retinitis Pigmentosa in Mice

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