Leber Congenital Amaurosis

Tsang, Stephen H.; Sharma, Tarun

doi:10.1007/978-3-319-95046-4_26

Cited by 59 publications

(51 citation statements)

References 3 publications

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“…Disease onset can be from early childhood, however, some patients do not exhibit symptoms until after the first decade of life [290][291][292]. Additional CRB1 clinically relevant features include macular atrophy, keratoconus, Coats-like exudative vasculopathy, RP without PPRPE, pigmented paravenous chorioretinal atrophy, and nanophthalmos [288,[293][294][295][296][297].…”

Section: Crb1 and Leber Congenital Amaurosismentioning

confidence: 99%

Retinogenesis of the Human Fetal Retina: An Apical Polarity Perspective

Quinn

Wijnholds

2019

Genes

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The Crumbs complex has prominent roles in the control of apical cell polarity, in the coupling of cell density sensing to downstream cell signaling pathways, and in regulating junctional structures and cell adhesion. The Crumbs complex acts as a conductor orchestrating multiple downstream signaling pathways in epithelial and neuronal tissue development. These pathways lead to the regulation of cell size, cell fate, cell self-renewal, proliferation, differentiation, migration, mitosis, and apoptosis. In retinogenesis, these are all pivotal processes with important roles for the Crumbs complex to maintain proper spatiotemporal cell processes. Loss of Crumbs function in the retina results in loss of the stratified appearance resulting in retinal degeneration and loss of visual function. In this review, we begin by discussing the physiology of vision. We continue by outlining the processes of retinogenesis and how well this is recapitulated between the human fetal retina and human embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal organoids. Additionally, we discuss the functionality of in utero and preterm human fetal retina and the current level of functionality as detected in human stem cell-derived organoids. We discuss the roles of apical-basal cell polarity in retinogenesis with a focus on Leber congenital amaurosis which leads to blindness shortly after birth. Finally, we discuss Crumbs homolog (CRB)-based gene augmentation.

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Section: Crb1 and Leber Congenital Amaurosismentioning

confidence: 99%

Retinogenesis of the Human Fetal Retina: An Apical Polarity Perspective

Quinn

Wijnholds

2019

Genes

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“…Down syndrome increases the risk of keratoconus progression, thereby increasing the risk of acute hydrops [20]. Retinitis pigmentosa, Leber Congenital Amaurosis (LCA), floppy eye lid syndrome, and Ehler-Danlos syndrome are other risk factors for progressive keratoconus, which are followed by the incident of hydrops [21,22,23,24]. Pregnancy and lactation are also the critical but temporary risk factors [25].…”

Section: Predisposing Factorsmentioning

confidence: 99%

Acute Hydrops and Its Management

Subudhi¹,

Patro²,

Subudhi³

2020

Eyesight and Medical Image Cognition - Recent Advances and New Perspectives [Working Title]

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Acute hydrops is a well-known complication of keratoconus. It usually manifests as sudden onset loss of vision. Mostly presents in the pubertal age group. Allergic conjunctivitis associated with eye rubbing is the most substantial risk factor. Primary pathology being stromal lysis, which triggers the progression of cone, causing an undue stretch on Descemet Membrane, eventually resulting in its splitting and stromal imbibition of aqueous through these ruptures. Clinical signs are circum-cillary congestion and thick/edematous cornea with obscuration of the anterior segment. Conservative therapy delays wound healing; hence early surgical intervention is recommended globally for faster resolution of stromal edema. Long-standing corneal edema mounts to corneal perforation and neovascularisation of cornea. Compressive suture, non expansile intracameral gas injection, Deep anterior lamellar keratoplasty, and mini Descemet membrane keratoplasty are various management modalities reported in literature. Acute hydrops could be well prevented with early identification of progressive keratoconus and halting its progression.

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“…One example is Leber congenital amaurosis (LCA) which is one of the major causes of blindness among children. Mutations in the CEP290, CRB1, GUCY2D or RPE65 are the most common causes of this disorder (Tsang and Sharma 2018). In 2017, U.S. Food and Drug Administration (FDA) approved Luxturna (Spark Therapeutics) a gene transfer therapy where a healthy copy of RPE65 is delivered to the diseased retina using an Adeno-Associated Viral vector (Smalley 2017).…”

Section: Repairing Faulty Genomesmentioning

confidence: 99%

Gene editing in translational research.

Güell

2019

rbd

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DNA read and write technologies have accelerated biotechnology at an unprecedented pace. This enhanced capacity to engineer living beings has accelerated not only scientific research, but also the translation into novel therapies. New approved medicinal products include the correction of the diseased genome and synthetic enhancement to fight diseases. These practices are widely supported socially and scientifically. Applications beyond therapy have also be attempted. In 2018, researcher He Jiankui reported on the edition of human germline during the Second International Summit on Human Genome Editing. On the other hand, during the last years, there have also been attempts at somatic genetic enhancement without the provision of detailed outcomes. Reading and writing DNA empowers us to change our world, even ourselves. The social benefits may be enormous. We need to accelerate the debate, including the stakeholders, to foster a responsible use of these technologies and maximize the positive impact on society.

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Leber Congenital Amaurosis

Cited by 59 publications

References 3 publications

Retinogenesis of the Human Fetal Retina: An Apical Polarity Perspective

Retinogenesis of the Human Fetal Retina: An Apical Polarity Perspective

Acute Hydrops and Its Management

Gene editing in translational research.

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