Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations

Sahel, José‐Alain; Marazova, Katia; Audo, Isabelle

doi:10.1101/cshperspect.a017111

Cited by 188 publications

(170 citation statements)

References 181 publications

(185 reference statements)

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“…1–3 Pathology in AMD and some forms of RP can involve dysfunction of the retinal pigment epithelium (RPE). 1–3 Multiple animal models have been used to investigate such RPE dysfunction and test potential therapies.…”

mentioning

confidence: 99%

Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography

Ryals

Andrews

Datta

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PurposeProspective treatments for age-related macular degeneration and inherited retinal degenerations are commonly evaluated in the Royal College of Surgeons (RCS) rat before translation into clinical application. Historically, retinal thickness obtained through postmortem anatomic assessments has been a key outcome measure; however, utility of this measurement is limited because it precludes the ability to perform longitudinal studies. To overcome this limitation, the present study was designed to provide a baseline longitudinal quantification of retinal thickness in the RCS rat by using spectral-domain optical coherence tomography (SD-OCT).MethodsHorizontal and vertical linear SD-OCT scans centered on the optic nerve were captured from Long-Evans control rats at P30, P60, P90 and from RCS rats between P17 and P90. Total retina (TR), outer nuclear layer+ (ONL+), inner nuclear layer (INL), and retinal pigment epithelium (RPE) thicknesses were quantified. Histologic sections of RCS retina obtained from P21 to P60 were compared to SD-OCT images.ResultsIn RCS rats, TR and ONL+ thickness decreased significantly as compared to Long-Evans controls. Changes in INL and RPE thickness were not significantly different between control and RCS retinas. From P30 to P90 a subretinal hyperreflective layer (HRL) was observed and quantified in RCS rats. After correlation with histology, the HRL was identified as disorganized outer segments and the location of accumulated debris.ConclusionsRetinal layer thickness can be quantified longitudinally throughout the course of retinal degeneration in the RCS rat by using SD-OCT. Thickness measurements obtained with SD-OCT were consistent with previous anatomic thickness assessments. This study provides baseline data for future longitudinal assessment of therapeutic agents in the RCS rat.

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confidence: 99%

Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography

Ryals

Andrews

Datta

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…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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“…2 Retinal degenerative diseases causing outer retina pathology are a major cause of blindness and the most common neural degenerative disease. 3,4 These diseases either exhibit Mendelian patterns of inheritance or, in the case of AMD, genetic factors, predispose to disease. The various inherited forms show different clinical presentation and age of onset, from birth, such as in Leber congenital amaurosis, or with juvenile or adult onset, such as in retinitis pigmentosa (RP), which may also occur in association with other nonocular conditions, such as the Usher syndrome.…”

Section: Retinal Degenerative Diseasementioning

confidence: 99%

Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement

Foggia

Makwana

Ali³

et al. 2016

Journal of Ocular Pharmacology and Therapeutics

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Stem cell therapies are being explored as potential treatments for retinal disease. How to replace neurons in a degenerated retina presents a continued challenge for the regenerative medicine field that, if achieved, could restore sight. The major issues are: (i) the source and availability of donor cells for transplantation; (ii) the differentiation of stem cells into the required retinal cells; and (iii) the delivery, integration, functionality, and survival of new cells in the host neural network. This review considers the use of induced pluripotent stem cells (iPSC), currently under intense investigation, as a platform for cell transplantation therapy. Moreover, patientspecific iPSC are being developed for autologous cell transplantation and as a tool for modeling specific retinal diseases, testing gene therapies, and drug screening.

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Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations

Cited by 188 publications

References 181 publications

Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography

Long-term Characterization of Retinal Degeneration in Royal College of Surgeons Rats Using Spectral-Domain Optical Coherence Tomography

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement

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