Epidemiology of Mutations in the 65-kDa Retinal Pigment Epithelium (RPE65) Gene-Mediated Inherited Retinal Dystrophies: A Systematic Literature Review

Sallum, Juliana Maria Ferraz; Kaur, Vinay Preet; Shaikh, J.; Banhazi, Judit; Spera, Claudio; Aouadj, Celia; Viriato, Daniel; Fischer, Manuel

doi:10.1007/s12325-021-02036-7

Cited by 21 publications

(19 citation statements)

References 105 publications

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“…Currently, no remedy exists for the various forms of RP, although several different approaches have been tried and many others are currently under investigation (152,153). The sole important exception is represented by voretigene neparvovec, an AAVbased gene therapy specifically designed for the treatment of retinal dystrophies caused by RPE65 bi-allelic mutations, although the latter ones account only for a very small proportion of all RP cases (152)(153)(154).…”

Section: Retinitis Pigmentosamentioning

confidence: 99%

More than meets the eye: The role of microglia in healthy and diseased retina

et al. 2022

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Microglia are the main resident immune cells of the nervous system and as such they are involved in multiple roles ranging from tissue homeostasis to response to insults and circuit refinement. While most knowledge about microglia comes from brain studies, some mechanisms have been confirmed for microglia cells in the retina, the light-sensing compartment of the eye responsible for initial processing of visual information. However, several key pieces of this puzzle are still unaccounted for, as the characterization of retinal microglia has long been hindered by the reduced population size within the retina as well as the previous lack of technologies enabling single-cell analyses. Accumulating evidence indicates that the same cell type may harbor a high degree of transcriptional, morphological and functional differences depending on its location within the central nervous system. Thus, studying the roles and signatures adopted specifically by microglia in the retina has become increasingly important. Here, we review the current understanding of retinal microglia cells in physiology and in disease, with particular emphasis on newly discovered mechanisms and future research directions.

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Section: Retinitis Pigmentosamentioning

confidence: 99%

More than meets the eye: The role of microglia in healthy and diseased retina

et al. 2022

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“…Regarding the RPE65 gene, numerous pathogenic variants have been identified in humans. Many of these variants introduce a nonsense or a missense mutation capable of affecting protein expression or enzyme function and are associated with a spectrum of inherited retinal diseases ranging from Leber’s congenital amaurosis (LCA) to retinitis pigmentosa (RP) 5 . Voretigene neparvovec (Luxturna™) is the first gene therapy approved for the treatment of retinal degeneration 6 ; it is delivered as an adeno-associated virus (AAV2)-based genetic treatment in a subretinal injection to patients with an inherited retinal dystrophy caused by biallelic mutations in the RPE65 gene 7 .…”

Section: Introductionmentioning

confidence: 99%

An in silico toolbox for the prediction of the potential pathogenic effects of missense mutations in the dimeric region of h RPE65

Poli

Demontis

Sodi

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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h RPE65 is a fundamental enzyme of the retinoid visual cycle, and many missense mutations affecting its expression or function are associated with a wide range of diseases. Many h RPE65 missense mutations lack a clear pathogenicity classification or are labelled as VUS. In this context, we recently developed a protocol based on µs-long molecular dynamics simulations to study the potential pathogenic effect of h RPE65 missense mutations. In the present work, the structure-based protocol was integrated with a h RPE65-tailored consensus bioinformatics strategy, named ConPath, that showed high performance in predicting known pathogenic/benign h RPE65 missense mutations. The combined strategy was used to perform a multi-level evaluation of the potential pathogenicity of 13 different h RPE65 VUS, which were classified based on their likelihood of pathogenic effect. The obtained results provide information that may support the reclassification of these VUS and help clinicians evaluate the eligibility for gene therapy of patients diagnosed with such variants.

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“…While the visual and functional impairments associated with RP have been shown to lead to reduced HRQoL for patients, 7 quantitative data on this aspect are difficult to collect by observational or clinical research due to the relatively low prevalence of this condition (with estimates ranging from 11.09 to 26.43 per 100,000 worldwide, dependent on region and study). 8 Quantitative data in the form of health state utility values are required for activities such as modelling the burden of disease on those affected or the cost-effectiveness of new interventions, and therefore potentially contribute to new treatment options being made available to patients. 9 …”

Section: Introductionmentioning

confidence: 99%

Elicitation of Health State Utility Values in Retinitis Pigmentosa by Time Trade-off in the United Kingdom

O'Brien¹,

Enstone²,

Bridge³

et al. 2023

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Introduction Retinitis pigmentosa (RP) is an inherited retinal pathology associated with “night blindness” and progressive loss of peripheral vision, in some cases leading to complete blindness. Health state utility values are required for activities such as modelling disease burden or the cost-effectiveness of new interventions. The current study aimed to generate utility values for health states of varying levels of functional vision in RP, with members of the general public in the UK. Methods Five health states were defined according to standard clinical measures of visual ability. Health state descriptions were developed following interviews with patients with RP in the UK (n=5). Further interviews were conducted for confirmation with healthcare professionals with specific experience of managing patients with RP in the UK (n=2). Interviews with members of the general public in the UK were conducted to value health states. A time trade-off (TTO) process based on the established Measurement and Valuation of Health (MVH) protocol was used. Due to the ongoing COVID-19 pandemic, all interviews were web-enabled and conducted 1:1 by a trained moderator. Results In total, n=110 TTO interviews were conducted with members of the UK general public. Mean TTO utility values followed the logical and expected order, with increasing visual impairment leading to decreased utility. Mean values varied between 0.78 ± 0.20 (“moderate impairment”), and 0.33 ± 0.26 (“hand motion” to “no light perception”). Supplementary visual analogue scale (VAS) scores also followed the logical and expected order: mean VAS values varied between 47.95 ± 15.38 (“moderate impairment”) and 17.22 ± 12.49 in (“hand motion” to “no light perception”). Discussion These data suggest that individuals living with RP have substantially impaired quality of life. Utility values for RP have been elicited here using a method and sample that is suitable for economic modelling and health technology assessment purposes.

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Epidemiology of Mutations in the 65-kDa Retinal Pigment Epithelium (RPE65) Gene-Mediated Inherited Retinal Dystrophies: A Systematic Literature Review

Cited by 21 publications

References 105 publications

More than meets the eye: The role of microglia in healthy and diseased retina

More than meets the eye: The role of microglia in healthy and diseased retina

An in silico toolbox for the prediction of the potential pathogenic effects of missense mutations in the dimeric region of h RPE65

Elicitation of Health State Utility Values in Retinitis Pigmentosa by Time Trade-off in the United Kingdom

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