Ciliary neurotrophic factor (CNTF) delivery to retina: an overview of current research advancements

Ghasemi, Maryam; Arezoumand, Khatereh Saei; Motlagh, Behzad Fallahi; Zarghami, Nosratollah

doi:10.1080/21691401.2017.1391820

Cited by 15 publications

(16 citation statements)

References 141 publications

(159 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CNTF is a common extracellular factor that prevents excessive production of opsins, photoreceptors of outer segments, and 11-cis-retinal to protect rods and cones from photodamage (Li et al, 2018). Intraocular administration of CNTF has been found to attenuate photoreceptor degeneration and preserve retinal functions in animal research models of inherited or induced retinal disease (Ghasemi et al, 2018). Studies have suggested that the CNTF plays an important role in the regeneration and repair of the optic nerve after injury (Leibinger et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Association of retinal nerve fiber abnormalities with serum CNTF and cognitive functions in schizophrenia patients

Liu

Huang

Tong

et al. 2020

PeerJ

View full text Add to dashboard Cite

Background Recent studies have reported reductions in retinal nerve fiber layers (RNFL) in schizophrenia. Ciliary neurotrophic factor (CNTF) has shown protective effects on both the neurogenesis and retina. This study aimed at investigating retinal abnormalities and establishing their correlation with serum CNTF and cognitive impairments in schizophrenic Chinese patients. Methods In total, 221 patients diagnosed with schizophrenia and 149 healthy controls were enrolled. Serum CNTF and clinical features of patients were investigated. Cognitive functions were evaluated with Repeatable Battery for the Assessment of Neuropsychology Status (RBANS). RNFL thickness and macular thickness (MT) of both eyes were measured with optical coherence tomography (OCT). T-tests and analysis of covariance were used to compare the variables between the patient and control groups, while multiple linear regression analysis was performed to determine the associations of RNFL thickness, CNTF and cognitive impairments. Results RNFL was found thinner in patients than in healthy controls (right: 88.18 ± 25.84 µm vs.102.13 ± 14.32 µm, p = 0.001; left: 92.84 ± 13.54 µm vs.103.71 ± 11.94 µm, p < 0.001). CNTF was lower in the schizophrenia group (1755.45 ± 375.73 pg/ml vs. 1909.99 ± 368.08 pg/ml, p = 0.001). Decline in RNFL thickness was found correlated with course of illness and serum CNTF in patients (all p < 0.05). Similarly, cognitive functions such as immediate memory and visuospatial functions were also found correlated with decline in RNFL thickness. Conclusion Decline in RNFL thickness was associated with cognitive impairments of schizophrenia and CNFT serum concentration. The possibility of reduction in RNFL thickness as a biomarker for schizophrenia needs to be further examined.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of retinal nerve fiber abnormalities with serum CNTF and cognitive functions in schizophrenia patients

Liu

Huang

Tong

et al. 2020

PeerJ

View full text Add to dashboard Cite

show abstract

“…Despite a large body of data which have demonstrated the neuroprotective features of neurotrophins and antioxidants, delivery of these molecules into the eye remains a major challenge in translating our current knowledge into clinical practice. Direct injections of neurotrophins into the vitreous are not practical given their low bioavailability and short halflife, for which gene therapies, using adenoviral, adenoassociated (AVV) and lentiviral vectors as methods to deliver these molecules into the retina have been actively explored 92 ; however, gene therapies so far have been limited to the introduction of single molecules, and effective neuroprotection of the retina may not be achieved by either injection of individual trophic factors or gene therapies targeting single neurotrophins. An example of these approaches is illustrated by early studies that utilized intraocular implants of encapsulated cells genetically modified to secrete CNTF.…”

Section: Potential Of Müller Glia As a Vehicle To Deliver Neuroprotecmentioning

confidence: 99%

Potential of Müller Glia for Retina Neuroprotection

Eastlake

Luis

Limb

2019

Current Eye Research

View full text Add to dashboard Cite

Müller glia constitute the main glial cells of the retina. They are spatially distributed along this tissue, facilitating their close membrane interactions with all retinal neurons. Müller glia are characterized by their active metabolic functions, which are neuroprotective in nature. Although they can become reactive under pathological conditions, leading to their production of inflammatory and neurotoxic factors, their main metabolic functions confer neuroprotection to the retina, resulting in the promotion of neural cell repair and survival. In addition to their protective metabolic features, Müller glia release several neurotrophic factors and antioxidants into the retinal microenvironment, which are taken up by retinal neurons for their survival. This review summarizes the Müller glial neuroprotective mechanisms and describes advances made on the clinical application of these factors for the treatment of retinal degenerative diseases. It also discusses prospects for the use of these cells as a vehicle to deliver neuroprotective factors into the retina. ARTICLE HISTORY

show abstract

“…The most clinically advanced, Renexus ® (NT-501; Neurotech Pharmaceuticals, Inc., Cumberland, RI, USA) is an implant with encapsulated, genetically engineered ARPE-19 cells, that secrete and maintain low concentrations of human CNTF in the vitreous over several years [ 19 ]. Its neuroprotective effects have been evaluated in patients with dry AMD [ 95 , 96 ], CNGB3-achromatopsia [ 97 ], glaucoma [ 98 ], retinitis pigmentosa [ 5 , 19 , 99 ], and macular telangiectasia type 2 (MacTel 2) [ 100 ]. No efficacy was evident in CNGB3-achromatopsia patients [ 97 ], and only moderate efficacy was observed in RP patients and patients with geographic atrophy secondary to dry AMD [ 95 , 96 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization, Stability, and In Vivo Efficacy Studies of Recombinant Human CNTF and Its Permeation into the Neural Retina in Ex Vivo Organotypic Retinal Explant Culture Models

et al. 2020

View full text Add to dashboard Cite

Ciliary neurotrophic factor (CNTF) is one of the most studied neuroprotective agents with acknowledged potential in treating diseases of the posterior eye segment. Although its efficacy and mechanisms of action in the retina have been studied extensively, it is still not comprehensively understood which retinal cells mediate the therapeutic effects of CNTF. As with therapeutic proteins in general, it is poorly elucidated whether exogenous CNTF administered into the vitreous can enter and distribute into the retina and hence reach potentially responsive target cells. Here, we have characterized our purified recombinant human CNTF (rhCNTF), studied the protein’s in vitro bioactivity in a cell-based assay, and evaluated the thermodynamic and oligomeric status of the protein during storage. Biological activity of rhCNTF was further evaluated in vivo in an animal model of retinal degeneration. The retinal penetration and distribution of rhCNTF after 24 h was studied utilizing two ex vivo retina models. Based on our characterization findings, our rhCNTF is correctly folded and biologically active. Moreover, based on initial screening and subsequent follow-up, we identified two buffers in which rhCNTF retains its stability during storage. Whereas rhCNTF did not show photoreceptor preservative effect or improve the function of photoreceptors in vivo, this could possibly be due to the used disease model or the short duration of action with a single intravitreal injection of rhCNTF. On the other hand, the lack of in vivo efficacy was shown to not be due to distribution limitations; permeation into the retina was observed in both retinal explant models as in 24 h rhCNTF penetrated the inner limiting membrane, and being mostly observed in the ganglion cell layer, distributed to different layers of the neural retina. As rhCNTF can reach deeper retinal layers, in general, having direct effects on resident CNTF-responsive target cells is plausible.

show abstract

Ciliary neurotrophic factor (CNTF) delivery to retina: an overview of current research advancements

Cited by 15 publications

References 141 publications

Association of retinal nerve fiber abnormalities with serum CNTF and cognitive functions in schizophrenia patients

Association of retinal nerve fiber abnormalities with serum CNTF and cognitive functions in schizophrenia patients

Potential of Müller Glia for Retina Neuroprotection

Characterization, Stability, and In Vivo Efficacy Studies of Recombinant Human CNTF and Its Permeation into the Neural Retina in Ex Vivo Organotypic Retinal Explant Culture Models

Contact Info

Product

Resources

About