Therapeutic strategy for handling inherited retinal degenerations in a gene-independent manner using rod-derived cone viability factors

Léveillard, Thierry; Fridlich, Ram; Clérin, Emmanuelle; Aït-Ali, Najate; Millet-Puel, Géraldine; Jaillard, C.; Yang, Ying; Zack, Donald J.; Van-Dorsselaer, Alain; Sahel, José‐Alain

doi:10.1016/j.crvi.2013.12.002

Cited by 13 publications

(12 citation statements)

References 50 publications

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“…This can be achieved with either immune-suppressant or immunomodulatory drugs (Karlstetter et al, 2010). Another strategy includes the administration of protective molecules, such as rod-derived cone viability factors, to preserve cone-dependent central vision after rod death (Leveillard et al, 2014). In addition, the application of sub-retinal photovoltaic arrays that restore photoreceptor function can be applied when the inner retinal circuits are preserved (Light et al, 2014).…”

Section: Retinitis Pigmentosa (Rp)mentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

609

533

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The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.

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Section: Retinitis Pigmentosa (Rp)mentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

609

533

View full text Add to dashboard Cite

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“…Therapeutic interventions for dominant mutations additionally need a cellular depletion of the mutated endogenous copy. In addition, interventions to stop or delay the disease progression by applying neuroprotective factors (Trifunović et al, 2012; Froger et al, 2014; Léveillard et al, 2014) as well as substituting degenerated photoreceptors using cell transplantations (Jayakody et al, 2015) are also being tested extensively.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Biophysical Properties of Optogenetic Tools and Their Application for Vision Restoration Approaches

Klapper

Swiersy

Bamberg

et al. 2016

Front. Syst. Neurosci.

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Optogenetics is the use of genetically encoded light-activated proteins to manipulate cells in a minimally invasive way using light. The most prominent example is channelrhodopsin-2 (ChR2), which allows the activation of electrically excitable cells via light-dependent depolarization. The combination of ChR2 with hyperpolarizing-light-driven ion pumps such as the Cl− pump halorhodopsin (NpHR) enables multimodal remote control of neuronal cells in culture, tissue, and living animals. Very soon, it became obvious that this method offers a chance of gene therapy for many diseases affecting vision. Here, we will give a brief introduction to retinal function and retinal diseases; optogenetic vision restoration strategies will be highlighted. We will discuss the functional and structural properties of rhodopsin-based optogenetic tools and analyze the potential for the application of vision restoration.

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“…Approximately 1.5 to 2.5 million RP patients are affected worldwide (Dias et al, 2017;Hartong et al, 2006;Verbakel et al, 2018). The initial pathological feature is selective rod photoreceptor cell death, which is generally followed by loss of cone photoreceptors (Léveillard et al, 2014). Mutations in more than 70 genes have been linked to RP (Dias et al, 2017;https://sph.uth.edu/retnet/).…”

Section: Introductionmentioning

confidence: 99%

Large-scale Phenotypic Drug Screen Identifies Neuroprotectants in Zebrafish and Mouse Models of Retinitis Pigmentosa

Zhang

Chen

et al. 2020

Preprint

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Retinitis pigmentosa (RP) and associated inherited retinal diseases (IRDs) are caused by rod photoreceptor degeneration, necessitating therapeutics promoting rod photoreceptor survival. To address this, we tested compounds for neuroprotective effects in zebrafish and mouse RP models, reasoning drugs effective across species may translate better clinically. We first performed a large-scale phenotypic drug screen using a larval zebrafish model of inducible RP. 2,934 compounds, mostly humanapproved drugs, were tested across six concentrations. Statistically, 113 compounds achieved "hit" status. Secondary tests of 42 high-priority hits confirmed eleven lead compounds. Nine leads were then evaluated in mouse RP models, with six exhibiting neuroprotective effects. An analysis of potential mechanisms of action suggested complementary activities. Paired lead compound assays in zebrafish showed additive neuroprotective effects for the majority. These results highlight the value of crossspecies phenotypic drug discovery and suggest combinatorial drug therapies may provide enhanced therapeutic benefits for patients with RP and IRDs.

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Therapeutic strategy for handling inherited retinal degenerations in a gene-independent manner using rod-derived cone viability factors

Cited by 13 publications

References 50 publications

Glia–neuron interactions in the mammalian retina

Glia–neuron interactions in the mammalian retina

Biophysical Properties of Optogenetic Tools and Their Application for Vision Restoration Approaches

Large-scale Phenotypic Drug Screen Identifies Neuroprotectants in Zebrafish and Mouse Models of Retinitis Pigmentosa

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