CNTF and retina

Wen, Rong; Li, Yiwen; Sieving, Paul A.

doi:10.1016/j.preteyeres.2011.11.005

Cited by 185 publications

(143 citation statements)

References 135 publications

(220 reference statements)

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“…This observation suggests that these two manipulations, acute Nrl KO and CNTF delivery, may preserve rod photoreceptors via a related pathway. The neuroprotective mechanism of CNTF is unclear, but one hypothesis is that down-regulation of the rod phototransduction machinery reduces the metabolic stress on cells prone to degeneration (48). Down-regulation of rod genes in the acute Nrl KO may play a similar protective role.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming of adult rod photoreceptors prevents retinal degeneration

Montana¹,

Kolesnikov

Shen³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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A prime goal of regenerative medicine is to direct cell fates in a therapeutically useful manner. Retinitis pigmentosa is one of the most common degenerative diseases of the eye and is associated with early rod photoreceptor death followed by secondary cone degeneration. We hypothesized that converting adult rods into cones, via knockdown of the rod photoreceptor determinant Nrl, could make the cells resistant to the effects of mutations in rodspecific genes, thereby preventing secondary cone loss. To test this idea, we engineered a tamoxifen-inducible allele of Nrl to acutely inactivate the gene in adult rods. This manipulation resulted in reprogramming of rods into cells with a variety of cone-like molecular, histologic, and functional properties. Moreover, reprogramming of adult rods achieved cellular and functional rescue of retinal degeneration in a mouse model of retinitis pigmentosa. These findings suggest that elimination of Nrl in adult rods may represent a unique therapy for retinal degeneration.

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Section: Discussionmentioning

confidence: 99%

Reprogramming of adult rod photoreceptors prevents retinal degeneration

Montana¹,

Kolesnikov

Shen³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Enhancement of photoreceptor survival by CNTF has been demonstrated in multiple animal models of retinal degeneration, ranging from zebrafish to canine (2). Interestingly, CNTF is effective in rescuing retinal degeneration due to various causes, including mutations in genes expressed by photoreceptors or the retinal pigment epithelium (RPE), as well as those induced by strong light, neurotoxins, or antibodies.…”

mentioning

confidence: 99%

CNTF-mediated protection of photoreceptors requires initial activation of the cytokine receptor gp130 in Müller glial cells

Rhee¹,

Nusinowitz²,

Chao³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Ciliary neurotrophic factor (CNTF) acts as a potent neuroprotective agent in multiple retinal degeneration animal models. Recently, CNTF has been evaluated in clinical trials for the inherited degenerative disease retinitis pigmentosa (RP) and for dry agerelated macular degeneration (AMD). Despite its potential as a broad-spectrum therapeutic treatment for blinding diseases, the target cells of exogenous CNTF and its mechanism of action remain poorly understood. We have shown previously that constitutive expression of CNTF prevents photoreceptor death but alters the retinal transcriptome and suppresses visual function. Here, we use a lentivirus to deliver the same secreted human CNTF used in clinical trials to a mouse model of RP. We found that low levels of CNTF halt photoreceptor death, improve photoreceptor morphology, and correct opsin mislocalization. However, we did not detect corresponding improvement of retinal function as measured by the electroretinogram. Disruption of the cytokine receptor gp130 gene in Müller glia reduces CNTF-dependent photoreceptor survival and prevents phosphorylation of STAT3 and ERK in Müller glia and the rest of the retina. Targeted deletion of gp130 in rods also demolishes neuroprotection by CNTF and prevents further activation of Müller glia. Moreover, CNTF elevates the expression of LIF and endothelin 2, thus positively promoting Müller and photoreceptor interactions. We propose that exogenous CNTF initially targets Müller glia, and subsequently induces cytokines acting through gp130 in photoreceptors to promote neuronal survival. These results elucidate a cellular mechanism for exogenous CNTF-triggered neuroprotection and provide insight into the complex cellular responses induced by CNTF in diseased retinas.C iliary neurotrophic factor (CNTF) belongs to a small subfamily of cytokines and has long been recognized as a potent neuroprotective molecule in the vertebrate retina (1). Enhancement of photoreceptor survival by CNTF has been demonstrated in multiple animal models of retinal degeneration, ranging from zebrafish to canine (2). Interestingly, CNTF is effective in rescuing retinal degeneration due to various causes, including mutations in genes expressed by photoreceptors or the retinal pigment epithelium (RPE), as well as those induced by strong light, neurotoxins, or antibodies. In addition, CNTF prolongs the survival of retinal ganglion cells (3-5) and promotes axonal growth in optic nerve crush or transection models (6-8). Furthermore, CNTF may affect the physiology and survival of RPE cells (9, 10), which are critical in normal vision and retinal degenerative diseases. Based on its significant and broad neuroprotective effects in damaged retinas, a secreted form of human CNTF delivered from an encapsulated cell device has been tested in clinical trials and approved by the Food and Drug Administration (FDA) to treat retinitis pigmentosa (RP) and geographic atrophy (GA), a subset of age-related macular degeneration (AMD) (11-14). However, despite its clinical signifi...

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“…Wewnątrzgałkowy implant CNTF (ciliary neurotrophic factor) jest neurotroficznym czynnikiem produkowanym przez komórki nerwowe, który -jak wykazano w badaniach na zwierzętach -może pomóc w zachowaniu pręcików i czopków [34]. Birch i wsp.…”

Section: Wewnątrzgałkowy Implant Cntfunclassified

Postępowanie w zwyrodnieniu barwnikowym siatkówki – przegląd piśmiennictwa

Krasodomska

Lubiński

2017

Pomeranian J Life Sci

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Introduction: Progressive nature and lack of effective treatment of the retinitis pigmentosa (RP) leads to search for the new therapeutic methods to stop progression of the disease. The aim of this study is to review the current treatment modalities that may influence progression of RP. Materials and methods: Based on the results reported in the available literature, non-pharmacological and pharmacological investigation in RP has been reviewed. Results:The results of numerous studies indicate that so far there is no cure for RP. However, there are methods that can slow down progression of the disease. Conclusions:Therapeutic treatment of patients with RP should be focused on providing psychological care, education planning, assistance in making a decision about a future profession or having children. Ophthalmologists should provide partially sighted people with a complete list of available optical systems, as well as treat cataract and cysts macular changes often associated with RP. Keywords: retinitis pigmentosa; pharmacological treatment; non-pharmacological treatment. ABSTRAKT Wstęp:Postępujący przebieg zwyrodnienia barwnikowego (retinitis pigmentosa -RP) oraz brak skutecznego leczenia skła-nia do poszukiwania nowych metod terapeutycznych w celu zahamowania progresji choroby. Celem niniejszej pracy była analiza aktualnych sposobów leczenia, które mogą wpływać na przebieg RP. Materiały i metody: Na podstawie wyników opisanych w dostępnym piśmiennictwie dokonano przeglądu postępo-wania niefarmakologicznego i farmakologicznego w RP. Wyniki: Nie ma dotychczas skutecznego leczenia RP, istnieją jednak metody mogące mieć wpływ na spowolnienie postępu choroby.Wnioski: Postępowanie terapeutyczne u pacjentów z RP powinno być skoncentrowane na zapewnieniu opieki psychologicznej, zaplanowaniu kierunku edukacji, pomocy w wyborze przyszłego zawodu oraz podjęciu decyzji o posiadaniu potomstwa. Ze strony okulistycznej przedstawić należy przede wszystkim możliwości zastosowania systemów dla osób słabowidzą-cych, a także leczenia współistniejących z RP zaćmy i zmian drobnotorbielowatych plamki. Słowa kluczowe: zwyrodnienie barwnikowe siatkówki; postę-powanie farmakologiczne; postępowanie niefarmakologiczne. WSTĘPZwyrodnienie barwnikowe siatkówki (retinitis pigmentosa -RP) to schorzenie siatkówki z postępującą dystrofią systemu pręcikowego i czopkowego prowadzące do inwalidztwa wzrokowego. Jest najczęściej rozpoznawaną wrodzoną dystrofią siatkówki, której występowanie szacuje się na 1:4000 urodzeń [1,2,3]. Dziedziczenie RP może być autosomalnie dominujące (15-20%), autosomalnie recesywne (20-25%), sprzężone z chromosomem X (10-15%) oraz sporadyczne (40-55%). Naturalny przebieg RP jest najwolniejszy w formie autosomalnie dominującej, a najszybszy w formie sprzężonej z chromosomem X. Opisano ponad 40 mutacji genów związanych z RP [2].Kryteria diagnostyczne obejmują postępujące zaburzenie widzenia zmierzchowego (nyktalopia) oraz zawężanie się obwodowego pola widzenia. Powszechnie znana klasyczna triada objawów na dnie oka...

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CNTF and retina

Cited by 185 publications

References 135 publications

Reprogramming of adult rod photoreceptors prevents retinal degeneration

Reprogramming of adult rod photoreceptors prevents retinal degeneration

CNTF-mediated protection of photoreceptors requires initial activation of the cytokine receptor gp130 in Müller glial cells

Postępowanie w zwyrodnieniu barwnikowym siatkówki – przegląd piśmiennictwa

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