Attenuation of Inherited and Acquired Retinal Degeneration Progression with Gene-based Techniques

Cho, Galaxy Y.; Bolo, Kyle; Park, Karen Sophia; Sengillo, Jesse D.; Tsang, Stephen H.

doi:10.1007/s40291-018-0377-1

Cited by 6 publications

(4 citation statements)

References 91 publications

(119 reference statements)

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“…Some of these key differences are summarized in Table 1 . In general, gene-based therapies for monogenic IRDs are more specific, requiring targeting of specific genetic variants, pathways, and cell types/locations ( Garoon and Stout, 2016 ; Takahashi et al, 2018 ; Cho et al, 2019 ; Xu et al, 2021 ). This limits the potential treatment population for each therapy developed, and is a driver of increased cost.…”

Section: Inherited Versus Acquired Retinal Diseasementioning

confidence: 99%

Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and Progress

et al. 2021

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Acquired retinal diseases such as age-related macular degeneration and diabetic retinopathy rank among the leading causes of blindness and visual loss worldwide. Effective treatments for these conditions are available, but often have a high treatment burden, and poor compliance can lead to disappointing real-world outcomes. Development of new treatment strategies that provide more durable treatment effects could help to address some of these unmet needs. Gene-based therapeutics, pioneered for the treatment of monogenic inherited retinal disease, are being actively investigated as new treatments for acquired retinal disease. There are significant advantages to the application of gene-based therapeutics in acquired retinal disease, including the presence of established therapeutic targets and common pathophysiologic pathways between diseases, the lack of genotype-specificity required, and the larger potential treatment population per therapy. Different gene-based therapeutic strategies have been attempted, including gene augmentation therapy to induce in vivo expression of therapeutic molecules, and gene editing to knock down genes encoding specific mediators in disease pathways. We highlight the opportunities and unmet clinical needs in acquired retinal disease, review the progress made thus far with current therapeutic strategies and surgical delivery techniques, and discuss limitations and future directions in the field.

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Section: Inherited Versus Acquired Retinal Diseasementioning

confidence: 99%

Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and Progress

et al. 2021

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“…The field of IRDs is rapidly evolving, as other gene therapies are under development [ 1 , 18 ]. These changes pose new challenges to clinicians treating patients with IRDs, including pediatricians, child neuropsychiatrists, and general ophthalmologists.…”

Section: Introductionmentioning

confidence: 99%

A multidisciplinary approach to inherited retinal dystrophies from diagnosis to initial care: a narrative review with inputs from clinical practice

Murro,

Banfi,

Testa

et al. 2023

Orphanet J Rare Dis

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Background Non-syndromic inherited retinal dystrophies (IRDs) such as retinitis pigmentosa or Leber congenital amaurosis generally manifest between early childhood and late adolescence, imposing profound long-term impacts as a result of vision impairment or blindness. IRDs are highly heterogeneous, with often overlapping symptoms among different IRDs, and achieving a definite diagnosis is challenging. This narrative review provides a clinical overview of the non-syndromic generalized photoreceptor dystrophies, particularly retinitis pigmentosa and Leber congenital amaurosis. The clinical investigations and genetic testing needed to establish a diagnosis are outlined, and current management approaches are discussed, focusing on the importance of the involvement of an interdisciplinary team from diagnosis and initial care to long-term follow-up and support. Results The effective management of IRDs requires a multidisciplinary, and ideally interdisciplinary, team of experts knowledgeable about IRDs, with experienced professionals from fields as diverse as ophthalmology, neuropsychiatry, psychology, neurology, genetics, orthoptics, developmental therapy, typhlology, occupational therapy, otolaryngology, and orientation and mobility specialties. Accurate clinical diagnosis encompasses a range of objective and subjective assessments as a prerequisite for the genetic testing essential in establishing an accurate diagnosis necessary for the effective management of IRDs, particularly in the era of gene therapies. Improvements in genome sequencing techniques, such as next-generation sequencing, have greatly facilitated the complex process of determining IRD-causing gene variants and establishing a molecular diagnosis. Genetic counseling is essential to help the individual and their family understand the condition, the potential risk for offspring, and the implications of a diagnosis on visual prognosis and treatment options. Psychological support for patients and caregivers is important at all stages of diagnosis, care, and rehabilitation and is an essential part of the multidisciplinary approach to managing IRDs. Effective communication throughout is essential, and the patient and caregivers’ needs and expectations must be acknowledged and discussed. Conclusion As IRDs can present at an early age, clinicians need to be aware of the clinical signs suggesting visual impairment and follow up with multidisciplinary support for timely diagnoses to facilitate appropriate therapeutic or rehabilitation intervention to minimize vision loss.

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“…Thus, a tool that is sensitive to localized changes in retinal function would be most sensitive to the earliest effects of the disease and would be useful in early diagnosis. In addition, important emerging genetic and protein delivery therapies for progressive retinal disease employ local treatment of the retina via subretinal injections of the therapeutic agent [2][3][4]. Accurately measuring the effect of these localized treatments is critical to gene therapy research, including clinical trials, and to eventual patient monitoring.…”

Section: Introductionmentioning

confidence: 99%

Visualizing spatial differences in corneal electroretinogram potentials using a three-dimensional surface spline

Kunzer¹,

Derafshi²,

Hetling³

2021

J. Neural Eng.

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Objective. The spatial distribution of activity at the retina determines the spatial distribution of electroretinogram potentials at the cornea. Here a three-dimensional surface spline method is evaluated for interpolating corneal potentials between measurement points in multi-electrode electroretinography (meERG) data sets. Approach. 25-channel meERG responses were obtained from rat eyes before and after treatment to create local lesions. A 3rd order surface spline was used to interpolate meERG values resulting in smooth color-coded maps of corneal potentials. Potential maps were normalized using standard score values. Pre- and post-treatment responses were characterized by spatial standard deviation and by difference-from-normal plots. Main results. The spatial standard deviation for eyes with local lesions were significantly higher than for healthy eyes. The 3rd order spline resulted in well-behaved corneal potential maps that maintained low error rate when up to 30% of recording channels were excluded from analysis. Post-normalization, responses could be combined within experimental groups, and individual eyes with lesions were clearly distinguished from the healthy-eye mean response. A 3rd order surface spline is an acceptable means of interpolating meERG potentials to create corneal potential maps. The spatial standard deviation is more sensitive to local dysfunction than absolute amplitudes. Significance. This work demonstrates solutions to key challenges in the recording and analysis of meERG responses: visualization, normalization, channel loss, and identification of abnormal responses. Continued development of the meERG technique is relevant to research and clinical applications, especially where local dysfunction (early progressive disease) or local therapeutic effect (subretinal injection) is of interest.

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Attenuation of Inherited and Acquired Retinal Degeneration Progression with Gene-based Techniques

Cited by 6 publications

References 91 publications

Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and Progress

Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and Progress

A multidisciplinary approach to inherited retinal dystrophies from diagnosis to initial care: a narrative review with inputs from clinical practice

Visualizing spatial differences in corneal electroretinogram potentials using a three-dimensional surface spline

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