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Metabolomics facilitates differential diagnosis in common inherited retinal degenerations by exploring their profiles of serum metabolites
Diagnosing inherited retinal degeneration is challenging. This exploratory study showed that metabolomic profiles differ among different subtypes of IRD, and potential biomarkers could be identified to facilitate diagnosis workflow in the near future.
- Wei-Chieh Wang
- , Chu-Hsuan Huang
- & Ta-Ching Chen
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Article
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The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision
Motile and non-motile cilia have distinct functions and protein complexes associated with them. Here, the authors show the conserved protein CFAP20 is important for both motile and non-motile cilia and is distinct from other ciliopathy-associated domains or macromolecular complexes.
- Paul W. Chrystal
- , Nils J. Lambacher
- & Michel R. Leroux
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Structural basis for transthyretin amyloid formation in vitreous body of the eye
Systemic ATTR amyloidosis causes the abnormal accumulation of ATTR fibrils formed from the human plasma protein transthyretin (TTR) in multiple organs including the eye. Here, the authors present a 3.2 Å cryo-EM structure of an ATTR fibril isolated from the vitreous body of an ATTR patient’s eye and discuss the mechanism for the structural conversion of TTR into a fibrillar form.
- Irina Iakovleva
- , Michael Hall
- & A. Elisabeth Sauer-Eriksson
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Mirtron-mediated RNA knockdown/replacement therapy for the treatment of dominant retinitis pigmentosa
Rhodopsin-related dominant retinitis pigmentosa is a degenerative disease of the retina of the eye for which there is no current treatment. In this study, the authors use a novel form of RNA-interference- artificial mirtrons- to slow retinal degeneration in a mouse model of the disease.
- Harry O. Orlans
- , Michelle E. McClements
- & Robert E. MacLaren
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Aberrant TGF-β1 signaling activation by MAF underlies pathological lens growth in high myopia
High myopia is associated with lens changes, but the underlying mechanisms are unclear. Here, the authors show increased equatorial diameter of the lens in subjects affected by high myopia, and find that these changes are associated with an increase in crystallin expression driven by the transcription factor MAF and TGF-β1 signaling.
- Xiangjia Zhu
- , Yu Du
- & Yi Lu
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Single AAV-mediated mutation replacement genome editing in limited number of photoreceptors restores vision in mice
Replacing mutant genes with wildtype copies using adeno-associated virus (AAV) has been explored for the treatment of inherited retinopathies, but the low cargo limit restricts its use. Here the authors describe a single AAV platform that allows local replacement of a mutated sequence with its wildtype counterpart, based on combined CRISPR-Cas9 and micro-homology-mediated end joining.
- Koji M. Nishiguchi
- , Kosuke Fujita
- & Toru Nakazawa
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A frequent variant in the Japanese population determines quasi-Mendelian inheritance of rare retinal ciliopathy
Genetic variants in RP1 can cause hereditary retinal degeneration (HRD). Here, in a genomic screen of 331 Japanese HRD patients, the authors identify a near-polymorphic RP1 variant that causes Mendelian HRD in trans with an Alu insertion and otherwise is associated with HRD according to a complex model of inheritance.
- Konstantinos Nikopoulos
- , Katarina Cisarova
- & Carlo Rivolta
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Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases
Reduced central corneal thickness (CCT) is observed in common eye diseases as well as in rare Mendelian disorders. Here, in a cross-ancestry GWAS, the authors identify 19 novel genetic loci associated with CCT, a subset of which is involved in rare corneal or connective tissue disorders.
- Adriana I. Iglesias
- , Aniket Mishra
- & Stuart MacGregor
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Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1
LOXL1 is a genetic risk factor for pseudoexfoliation syndrome of the eye but a causal variant has not been identified. Here, Pasutto et al., find intronic LOXL1 risk variants influence transcription factor binding and alternative splicing of LOXL1 in affected tissues reducing levels of LOXL1mRNA.
- Francesca Pasutto
- , Matthias Zenkel
- & Ursula Schlötzer-Schrehardt
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Article
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Cataract-associated P23T γD-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH
Aggregation of eye lens proteins leads to cataracts, a major cause of blindness. Here the authors use solid state NMR to probe the structure of γD-crystallin eye lens proteins aggregates, which are found to retain a native-like conformation.
- Jennifer C. Boatz
- , Matthew J. Whitley
- & Patrick C. A. van der Wel
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Article
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SLC7A14 linked to autosomal recessive retinitis pigmentosa
Retinitis pigmentosa is the leading cause of inherited blindness worldwide. Here, the authors use exome sequencing to identify mutations in SLC7A14that may be linked to the disease, and provide functional support for the role of this gene in retinal development and visual function in mice and zebrafish.
- Zi-Bing Jin
- , Xiu-Feng Huang
- & Jia Qu
Ciliary tip actin dynamics regulate photoreceptor outer segment integrity