Ocular and systemic findings in a survey of aniridia subjects

Netland, Peter A.; Scott, Michele L.; Boyle, John W.; Lauderdale, James D.

doi:10.1016/j.jaapos.2011.07.009

Cited by 68 publications

(62 citation statements)

References 25 publications

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“…Most if not all individuals with aniridia will develop a keratopathy known as aniridia-related keratopathy (ARK), which is caused by a breakdown of the corneal epithelium and invasion of conjunctival cells (Holland et al, 2003; Mayer et al, 2003; Netland et al, 2011). To assess the effect of pax6 mutations in frogs compared to mammals, histological sections of cornea were compared to those from Pax6 Sey-Neu /+ mice and the cornea of an individual with aniridia (Fig.…”

Section: Resultsmentioning

confidence: 99%

Xenopus pax6 mutants affect eye development and other organ systems, and have phenotypic similarities to human aniridia patients

Nakayama

Fisher

Nakajima

et al. 2015

Developmental Biology

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SUMMARY Mutations in the Pax6 gene cause ocular defects in both vertebrate and invertebrate animal species, and the disease aniridia in humans. Despite extensive experimentation on this gene in multiple species, including humans, we still do not understand the earliest effects on development mediated by this gene. This prompted us to develop pax6 mutant lines in Xenopus tropicalis taking advantage of the utility of the Xenopus system for examining early development and in addition to establish a model for studying the human disease aniridia in an accessible lower vertebrate. We have generated mutants in pax6 by using Transcription Activator-Like Effector Nuclease (TALEN) constructs for gene editing in X. tropicalis. Embryos with putative null mutations show severe eye abnormalities and changes in brain development, as assessed by changes in morphology and gene expression. One gene that we found is downregulated very early in development in these pax6 mutants is myc, a gene involved in pluripotency and progenitor cell maintenance and likely a mediator of some key pax6 functions in the embryo. Changes in gene expression in the developing brain and pancreas reflect other important functions of pax6 during development. In mutations with partial loss of pax6 function eye development is initially relatively normal but froglets show an underdeveloped iris, similar to the classic phenotype (aniridia) seen in human patients with PAX6 mutations. Other eye abnormalities observed in these froglets, including cataracts and corneal defects, are also common in human aniridia. The frog model thus allows us to examine the earliest deficits in eye formation as a result of pax6 lesions, and provides a useful model for understanding the developmental basis for the aniridia phenotype seen in humans.

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Section: Resultsmentioning

confidence: 99%

Xenopus pax6 mutants affect eye development and other organ systems, and have phenotypic similarities to human aniridia patients

Nakayama

Fisher

Nakajima

et al. 2015

Developmental Biology

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“…Glaucoma in aniridia occurs in early adulthood, but may also occur in infants and toddlers [50]. The incidence ranges from 6% to 75% [1].…”

Section: Clinical Manifestations and Managementmentioning

confidence: 99%

“…Genitourinary findings are cryptorchidism, ambiguous genitalia, and streak ovaries [71]. Obesity has also been observed in most of these patients [50, 71]. Therefore, when an infant presents with sporadic aniridia and genitourinary abnormalities, a molecular diagnosis must be made to exclude the deletion encompassing the WT1 gene, so appropriate risk management can be put in place for management of potential of Wilms’ tumor.…”

Section: Clinical Manifestations and Managementmentioning

confidence: 99%

Congenital aniridia: etiology, manifestations and management

Samant

Chauhan

Lathrop

et al. 2016

Expert Review of Ophthalmology

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Summary Congenital aniridia manifests as total or partial absence of the iris caused most commonly by mutations in PAX6, FOXC1, PITX2, and CYP1B1. Recently two new genes, FOXD3 and TRIM44, have also been implicated in isolated studies. We discuss the genotype-phenotype correlations for the main implicated genes. Classic aniridia is a panocular condition, which includes aniridia, cataract, corneal pannus, foveal, and optic nerve hypoplasia associated with mutations in the PAX6 gene. Classical aniridia is due to PAX6 mutations, while other genes contribute to aniridia-like phenotypes. We review the challenges involved in the management of aniridia, and discuss various surgical interventions. The clinical importance of defining the genotype in cases of congenital aniridia has become acutely apparent with the advent of possible therapies for classical aniridia, which are discussed.

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“…PAX6 syndrome (OMIM 106210, ORPHA77) has panocular and progressive manifestations (macular and optic hypoplasia, corneal opacifications, cataract, glaucoma, progressive scar formation) and often systemic involvement (early onset diabetes, disturbance of diurnal rhythms, cerebral malformations, auditory abnormalities, renal insufficiency) (Bamiou et al ; Ihnatko et al ). There is congenital visual impairment with progressive loss of vision mainly due to the negative effects of limbal stem cell insufficiency (LSCI) (Gregory‐Evans et al ; Khan et al ; Lagali et al ; Le et al ; Netland et al ).…”

Section: Introductionmentioning

confidence: 99%

“…Abnormal tear film stability and Meibomian gland dysfunction are also observed in patients with aniridia. This can lead to dry eyes, recurrent corneal erosion and ulceration in aniridic patients (Gregory‐Evans et al ; Ihnatko et al ; Netland et al ; Seitz et al ). With the pannus forming peripherally, patients often show refractive changes and astigmatism and refractive correction can be difficult.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic impact of anterior segment angiography of limbal stem cell insufficiency in PAX6‐related aniridia

et al. 2018

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PAX6 is a master gene of ocular development and postnatal ocular equilibrium. Congenital aniridia is the hallmark of PAX6 gene haploinsufficiency (Chr. 11 p. 13), but PAX6-associated aniridia is a profound, progressive pan-ocular developmental disorder often leading to blindness. There is congenital visual impairment with advancing loss of vision mainly due to secondary glaucoma and to corneal blindness caused by limbal stem cell insufficiency (LSCI). LSCI leads to ARK (aniridia-related keratopathy), which typically develops in four stages. Incipient LSCI with vessels starting to grow into the cornea can be imaged by fluorescein anterior segment angiography, which enables fine vessels to be more easily detected than by routine slit lamp examination, especially in patients with nystagmus. Thus, clinical stage 1 ARK is often diagnosed at stage 2 by angiography. Corneal neovascularizations often start at the 12 and 6 positions and subsequently progress circumferentially, not at the 3 and 9 positions as previously believed. Anterior segment angiography can provide an easily standardizable tool for monitoring progress, treatment-induced regress or stabilization of ARK. Especially in children, angiography could be used to monitor new treatment regimens for reducing LSCI. Angiography could enable treatment to begin earlier to preserve corneal hemostasis. In addition, the fact that vascularization often starts at the subpalpebral 6 and 12 positions as opposed to the 3 and 9 positions raises more questions concerning factors that promote LSCI and related corneal injuries. Clin. Anat. 31:392-397, 2018. © 2018 Wiley Periodicals, Inc.

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Ocular and systemic findings in a survey of aniridia subjects

Cited by 68 publications

References 25 publications

Xenopus pax6 mutants affect eye development and other organ systems, and have phenotypic similarities to human aniridia patients

Xenopus pax6 mutants affect eye development and other organ systems, and have phenotypic similarities to human aniridia patients

Congenital aniridia: etiology, manifestations and management

Diagnostic impact of anterior segment angiography of limbal stem cell insufficiency in PAX6‐related aniridia

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