KIT ligand protects against both light-induced and genetic photoreceptor degeneration
Photoreceptor degeneration is a major cause of blindness and a considerable health burden during aging but effective therapeutic or preventive strategies have not so far become readily available. Here we show in mouse models that signaling through the tyrosine kinase receptor KIT protects photoreceptor cells against both light-induced and inherited retinal degeneration. Upon light damage, photoreceptor cells upregulate Kit ligand (KITL) and activate KIT signaling, which in turn induces nuclear accumulation of the transcription factor NRF2 and stimulates the expression of the antioxidant geneHmox1. Conversely, a viableKit mutation promotes light-induced photoreceptor damage, which is reversed by experimental expression ofHmox1. Furthermore, overexpression of KITL from a viral AAV8 vector prevents photoreceptor cell death and partially restores retinal function after light damage or in genetic models of human retinitis pigmentosa. Hence, application of KITL may provide a novel therapeutic avenue for prevention or treatment of retinal degenerative diseases.
Conclusions: This research provides an overview of symptoms experienced by patients with USH1 and highlights the dramatic impact these have on patients' lives, allowing the identification of concepts of importance when evaluating therapeutic treatments in development for RP. PMID: 32367747 [PubMed - as supplied by publisher]
ConclusionsVisual impairment due toRLBP1 RP has a substantial impact on physical functioning and daily activities. To adequately assess all important symptoms and associated functional impacts inRLBP1 RP, it is recommended to either modify one or more existing instruments or to develop a new non-syndromic RP specific instrument.
Usher syndrome includes a group of genetically and clinically heterogeneous autosomal recessive diseases, such as retinitis pigmentosa (RP) and sensorineural hearing loss. Usher syndrome type I (USHI) is characterized by profound hearing impairment beginning at birth, vestibular dysfunction, and unintelligible speech in addition to RP. The relationships between the Usher syndrome causing genes and the resultant phenotypes of Usher syndrome have not yet been fully elucidated. In the present study, we recruited a Chinese family with Usher syndrome and conducted paneled next-generation sequencing, Sanger sequencing, segregati...
Conclusions: We describe a case of retinitis pigmentosa associated with acne vulgaris and highlight the role of this systemic manifestation of retinol deficiency in confirming pathogenicity of the novel variant. Given the small size of the genomic RBP4 DNA (0.6kb), gene therapy using an adeno-associated viral vector with subretinal delivery has great potential to treat this severe childhood-onset blinding retinal disease. In addition, ubiquitous expression of RBP4 supports the development of in vitro functional assays to test the vector potency for clinical use. PMID: 32323592 [PubMed - as supplied by publisher]
Identification of novel USH2A mutations in patients with autosomal recessive retinitis pigmentosa via targeted next‑generation sequencing. Mol Med Rep. 2020 Apr 22;: Authors: Zhu X, Li X, Tian W, Yang Y, Sun K, Li S, Zhu X Abstract Retinitis pigmentosa (RP) is a group of inheritable blindness retinal diseases characterized by the death of photoreceptor cells and a gradual loss of peripheral vision. Mutations in Usher syndrome type 2 (USH2A) have been reported in RP with or without hearing loss. The present study aimed to identify causative mutations in a cohort of families with RP from China. A ...
CONCLUSION: Our study expanded the CDHR1 mutation spectrum of RP in the Chinese population, which might help to better understand RP molecular pathogenesis. PMID: 32277948 [PubMed - as supplied by publisher]
Conclusions: We have reported three new cases with pathogenic variants in PEX6 presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness-blindness association. PMID: 32214787 [PubMed - in process]
In a clinical trial, gene therapy for X-linked retinitis pigmentosa improved vision.
(University of Helsinki) A canine study carried out at the University of Helsinki has described a gene variant in the regulatory region of the retina resulting in the abnormal function of retinal genes and, eventually, in the loss of vision in dogs. The study can benefit the diagnostics and treatment of retinitis pigmentosa, a disease suffered by two million human beings globally.
ABSTRACT Degenerative retinal diseases such as retinitis pigmentosa, Stargardt ’ s macular dystrophy, and age-related macular degeneration are characterized by irreversible loss of vision due to direct or indirect photoreceptor damage. No effective treatments exist, but stem cell studies have shown promising results. Our aim with this review was to describe the types of stem cells that are under study, their effects, and the main clinical trials involving them.RESUMO As doen ças degenerativas da retina, como retinose pigmentar, distrofia macular de Stargardt e degeneração macular relaciona &agrav...