Let There Be Light: Gene and Cell Therapy for Blindness

Dalkara, Deniz; Goureau, Olivier; Marazova, Katia; Sahel, José‐Alain

doi:10.1089/hum.2015.147

Cited by 106 publications

(79 citation statements)

References 133 publications

(132 reference statements)

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“…The disorder has been the subject of much research and trials of novel therapies, including gene replacement and stem cell therapies are underway. 1 Nullizygosity for ABCA4, predicted to result in an absence of ABCA4 protein in the retina, has been observed previously to cause severe disease. [2][3][4] However, to our knowledge, the severity and range of phenotypic variability has not been studied in a large cohort.…”

mentioning

confidence: 85%

Phenotype and Progression of Retinal Degeneration Associated With Nullizigosity of ABCA4

Fakin

Robson

Fujinami

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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mentioning

confidence: 85%

Phenotype and Progression of Retinal Degeneration Associated With Nullizigosity of ABCA4

Fakin

Robson

Fujinami

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…14 Lastly, the knowledge of precise genetic defects can allow development of gene-based therapies for treatment of IRDs. 15 …”

mentioning

confidence: 99%

Molecular Diagnosis of Inherited Retinal Diseases in Indigenous African Populations by Whole-Exome Sequencing

Roberts

Ratnapriya

Plessis

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeA majority of genes associated with inherited retinal diseases (IRDs) have been identified in patients of European origin. Indigenous African populations exhibit rich genomic diversity, and evaluation of reported genetic mutations has yielded low returns so far. Our goal was to perform whole-exome sequencing (WES) to examine variants in known IRD genes in underrepresented African cohorts.MethodsWhole-exome sequencing was performed on 56 samples from 16 families with diverse IRD phenotypes that had remained undiagnosed after screening for known mutations using genotyping-based microarrays (Asper Ophthalmics). Variants in reported IRD genes were identified using WES and validated by Sanger sequencing. Custom TaqMan assays were used to screen for identified mutations in 193 unrelated indigenous Africans with IRDs.ResultsA total of 3494 variants were identified in 217 known IRD genes, leading to the identification of seven different mutations (including six novel) in six genes (RHO, PRPF3, PRPF31, ABCA4, CERKL, and PDE6B) in six distinct families. TaqMan screening in additional probands revealed identical homozygous CERKL and PDE6B variants in four more patients.ConclusionsThis is the first report of WES of patients with IRDs in indigenous African populations. Our study identified genetic defects in almost 40% of the families analyzed, significantly enhancing the molecular diagnosis of IRD in South Africa. Thus, WES of understudied cohorts seems to present an effective strategy for determining novel mutations in heterogeneous retinal diseases.

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“…Antibiotic agents are injected into the anterior chamber at the end of the surgical procedure (e.g., ceftazidime). diseases affecting children or young adults [22]. Among them, retinis pigmentosa is the most frequent and is due to the progressive degeneration of the rod photoreceptor cells in the retina [22,23].…”

Section: Infectious Diseasesmentioning

confidence: 99%

“…diseases affecting children or young adults [22]. Among them, retinis pigmentosa is the most frequent and is due to the progressive degeneration of the rod photoreceptor cells in the retina [22,23]. The progressive rod degeneration is later followed by abnormalities in the adjacent retinal pigment epithelium and the deterioration of cone photoreceptor cells.…”

Section: Infectious Diseasesmentioning

confidence: 99%

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Lafond

Aptel

Mestas

et al. 2016

Expert Opinion on Drug Delivery

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Introduction: Due to numerous anatomical and physiological barriers, ocular drug delivery remains a major limitation in the treatment of diseases such as glaucoma, macular degeneration or inflammatory diseases. To date, only invasive approaches provide clinically effective results. Ultrasound can be defined as the propagation of a high-frequency sound wave exposing the propagation media to mechanical and thermal effects. Ultrasound has been proposed as a non-invasive physical agent for increasing therapeutic agent delivery in various fields of medicine.Areas Covered: An update on recent advances in transscleral and transcorneal ultrasoundmediated drug delivery is presented. Efficient drug delivery is achieved in vitro, ex vivo and in vivo for various types of materials. Numerous studies indicate that efficacy is related to Downloaded by [University of Lethbridge] at 02:55 18 June 2016 2 cavitation. Although slight reversible effects can be observed on the corneal epithelium, efficient drug delivery can be performed without causing damage to the cornea. Expert Opinion: Recent developments prove the potential of ultrasound-mediated ocular drug delivery. Cavitation appears to be a preponderant mechanism, opening a way to treatment monitoring by cavitation measurement. Even if no clinical studies have yet been performed, the promising results summarized here are promoting developments toward clinical applications, particularly in assessing the safety of the technique. Article highlights box• Ocular drug delivery limits the treatment of numerous diseases because of anatomical and physiological barriers so that current techniques are either inefficient (5% of the dose reaching the interior of the eye) or invasive (intravitreal injections, implants).• Ultrasound offers the possibility of acting noninvasively on the sclera or cornea.• Both in vitro and in vivo experiments report an increase in transscleral and transcorneal drug delivery by applying ultrasound which could suggest an increased treatment efficacy.• The mechanism of enhanced drug delivery is attributable to cavitation, producing slight, reversible changes in tissues.• Slight reversible damages attributable could be found. Thus, with an efficient cavitation monitoring procedure, translation to the clinic should be encouraged, as no severe damage has been observed. Downloaded by [University of Lethbridge] at 02:55 18 June 2016 3• The strategy of dosing the ultrasound exposure on measured cavitation activity in relation with its calibrated bioeffects in terms of damages and efficacy is proposed.Also, future developments shall benefit from the experience of sonophoresis.

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Let There Be Light: Gene and Cell Therapy for Blindness

Cited by 106 publications

References 133 publications

Phenotype and Progression of Retinal Degeneration Associated With Nullizigosity of ABCA4

Phenotype and Progression of Retinal Degeneration Associated With Nullizigosity of ABCA4

Molecular Diagnosis of Inherited Retinal Diseases in Indigenous African Populations by Whole-Exome Sequencing

Ultrasound-mediated ocular delivery of therapeutic agents: a review

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