Neurotrophin Family Members as Neuroprotectants in Retinal Degenerations

Abed, Edoardo; Corbo, Giovanni; Falsini, Benedetto

doi:10.1007/s40259-014-0110-5

Cited by 10 publications

(6 citation statements)

References 107 publications

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“…In particular, this assessment may be critical for therapies aimed at preservation or restoration of photoreceptor function such as nutritional treatments [ 20 , 21 ], growth factor administration [ 22 – 25 ], and gene augmentation [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Correlation of Macular Focal Electroretinogram with Ellipsoid Zone Extension in Stargardt Disease

Abed

Placidi

Calandriello

et al. 2017

Journal of Ophthalmology

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Stargardt disease (STGD1) is the most common cause of inherited juvenile macular degeneration. This disease is characterized by a progressive accumulation of lipofuscin in the outer retina and subsequent loss of photoreceptors and retinal pigment epithelium. The aim of this study was to evaluate the relationship between cone photoreceptor function and structure in STGD1. Macular function was assessed by visual acuity measurement and focal electroretinogram (FERG) recording while spectral domain optical coherence tomography (SD-OCT) imaging was performed to evaluate the integrity of photoreceptors. FERG amplitude was significantly reduced in patients with Stargardt disease (p < 0.0001). The amplitude of FERG showed a negative relationship with interruption of ellipsoid zone (EZ) (R2 = 0.54, p < 0.0001) and a positive correlation with average macular thickness (AMT). Conversely, visual acuity was only weakly correlated with central macular thickness (CMT) (R2 = 0.12, p = 0.04). In conclusion, this study demonstrates that FERG amplitude is a reliable indicator of macular cone function while visual acuity reflects the activity of the foveal region. A precise assessment of macular cone function by FERG recording may be useful to monitor the progression of STGD1 and to select the optimal candidates to include in future clinical trials to treat this disease.

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Section: Discussionmentioning

confidence: 99%

Correlation of Macular Focal Electroretinogram with Ellipsoid Zone Extension in Stargardt Disease

Abed

Placidi

Calandriello

et al. 2017

Journal of Ophthalmology

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“…However, in the past 2–3 decades, many areas of experimental therapy have arisen and continue to expand significantly to prevent PR degeneration or restore visual function. These include: 1) neuroprotective therapy with direct application of various survival-promoting factors (Abed et al, 2015; Faktorovich et al, 1990; LaVail et al, 1992; Wen et al, 2012), 2) gene-based therapy of recessively and dominantly inherited RDs, as well as viral vector delivery vehicles (Acland et al, 2001; Bennett et al, 1996; Dalkara et al, 2016; Dalkara and Sahel, 2014; Farrar et al, 2012; Laemmli, 1970; Lau et al, 2000; Lewin et al, 1998; Thompson et al, 2015; Trapani et al, 2015; Yang et al, 2015), 3) nanoparticles that act as antioxidants and biodegradable microspheres as non-viral delivery vectors for drug, gene and trophic factor delivery (Adijanto and Naash, 2015; Fernandez-Sanchez et al, 2017; Trapani et al, 2014; Wong et al, 2015; Zarbin et al, 2013; Zulliger et al, 2015), 4) transplantation and cell-based therapy with the use of retinal, RPE and stem cells (Aramant and Seiler, 2002; Li and Turner, 1988; Seiler et al, 2017; Thompson et al, 2015; Yang et al, 2015; Zarbin, 2016), 5) the development of visual prostheses using silicon chip technology (da Cruz et al, 2016; Duncan et al, 2017; Marc et al, 2014; Stingl and Zrenner, 2013), and 6) the field of optogenetics (Dalkara and Sahel, 2014; Duebel et al, 2015; Marc et al, 2014; Zarbin et al, 2013). The need for animal models has increased concomitantly with this research.…”

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confidence: 99%

Phenotypic characterization of P23H and S334ter rhodopsin transgenic rat models of inherited retinal degeneration

LaVail

Nishikawa

Steinberg

et al. 2018

Experimental Eye Research

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We produced 8 lines of transgenic (Tg) rats expressing one of two different rhodopsin mutations in albino Sprague-Dawley (SD) rats. Three lines were generated with a proline to histidine substitution at codon 23 (P23H), the most common autosomal dominant form of retinitis pigmentosa in the United States. Five lines were generated with a termination codon at position 334 (S334ter), resulting in a C-terminal truncated opsin protein lacking the last 15 amino acid residues and containing all of the phosphorylation sites involved in rhodopsin deactivation, as well as the terminal QVAPA residues important for rhodopsin deactivation and trafficking. The rates of photoreceptor (PR) degeneration in these models vary in proportion to the ratio of mutant to wild-type rhodopsin. The models have been widely studied, but many aspects of their phenotypes have not been described. Here we present a comprehensive study of the 8 Tg lines, including the time course of PR degeneration from the onset to one year of age, retinal structure by light and electron microscopy (EM), hemispheric asymmetry and gradients of rod and cone degeneration, rhodopsin content, gene dosage effect, rapid activation and invasion of the outer retina by presumptive microglia, rod outer segment disc shedding and phagocytosis by the retinal pigmented epithelium (RPE), and retinal function by the electroretinogram (ERG). The biphasic nature of PR cell death was noted, as was the lack of an injury-induced protective response in the rat models. EM analysis revealed the accumulation of submicron vesicular structures in the interphotoreceptor space during the peak period of PR outer segment degeneration in the S334ter lines. This is likely due to the elimination of the trafficking consensus domain as seen before as with other rhodopsin mutants lacking the C-terminal QVAPA. The 8 rhodopsin Tg lines have been, and will continue to be, extremely useful models for the experimental study of inherited retinal degenerations.

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“…Furthermore, it has been demonstrated that NGF may increase outer retina oxygenation by modulating the expression of VEGF in the RGC layer [ 32 ]. As suggested by Abed et al [ 33 ], the increase of oxygen tension may prevent photoreceptors apoptosis in specific models and stages of retinal degeneration.…”

Section: Discussionmentioning

confidence: 95%

NGF eye-drops topical administration in patients with retinitis pigmentosa, a pilot study

et al. 2016

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Background Preclinical trials have shown beneficial effects of nerve growth factor (NGF) administration on visual function in animal models of retinitis pigmentosa (RP). The aim of this pilot study was to explore the potential efficacy of short term NGF eye drops treatment in patients affected by RP.Methods The trial consisted in 10 days daily administration of murine NGF as eye-drops for a total dose of 1 mg NGF/pt. Eight RP patients at an advanced stage of the disease were included in the trial. To monitor safety and potential adverse effects subjects underwent standard clinical measures and were requested to report any general or topic alterations following NGF assumption. Retinal function was assessed at baseline and after treatment by best-corrected visual acuity measurement (BCVA), macular focal electroretinogram (fERG) recording and Goldmann visual field testing.ResultsA transient tolerable local corneal irritation was the only adverse effect reported. fERG and BCVA remained within the limits determined by test–retest analysis of a large cohort of RP patients. Three patients reported a subjective feeling of improved visual performance. This was associated to a temporary enlargement of the visual field in all three patients and to improved fERG in two of the three.ConclusionsShort-term administration of NGF eye-drops caused neither significant adverse effects nor visual function losses in the tested RP patients. A minority of patients experienced an improvement of visual performance as shown by Goldmann visual field and fERG. This study supports the safety and possible efficacy of NGF eye-drops administration in RP patients.Trial registration: EudraCT n. 2008-004561-26

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Neurotrophin Family Members as Neuroprotectants in Retinal Degenerations

Cited by 10 publications

References 107 publications

Correlation of Macular Focal Electroretinogram with Ellipsoid Zone Extension in Stargardt Disease

Correlation of Macular Focal Electroretinogram with Ellipsoid Zone Extension in Stargardt Disease

Phenotypic characterization of P23H and S334ter rhodopsin transgenic rat models of inherited retinal degeneration

NGF eye-drops topical administration in patients with retinitis pigmentosa, a pilot study

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