Visual cycle protein RPE65 persists in new retinal cells during retinal regeneration of adult newt

2006 ◽  
Vol 495 (4) ◽  
pp. 391-407 ◽  
Author(s):  
Chikafumi Chiba ◽  
Akika Hoshino ◽  
Kenta Nakamura ◽  
Kanako Susaki ◽  
Yuka Yamano ◽  
...  
Keyword(s):  
Visual Cycle ◽  
Retinal Regeneration ◽  
Retinal Cells ◽  
Adult Newt

scholarly journals Cadherin Expression during Retinal Regeneration in the Adult Newt

2001 ◽  
Vol 18 (2) ◽  
pp. 145-149 ◽  
Author(s):  
Kiyonori Hirota ◽  
Yuko Kaneko ◽  
Gen Matsumoto ◽  
Yoshiro Hanyu
Keyword(s):  
Retinal Regeneration ◽  
Adult Newt

scholarly journals Implications of a Multi-Step Trigger of Retinal Regeneration in the Adult Newt

Biomedicines ◽  
2017 ◽  
Vol 5 (4) ◽  
pp. 25 ◽  
Author(s):  
Hirofumi Yasumuro ◽  
Keisuke Sakurai ◽  
Fubito Toyama ◽  
Fumiaki Maruo ◽  
Chikafumi Chiba
Keyword(s):  
Retinal Regeneration ◽  
Adult Newt

scholarly journals Retinoids in the visual cycle: Role of the retinal G protein-coupled receptor

2020 ◽  
pp. jlr.TR120000850 ◽  
Author(s):  
Elliot H Choi ◽  
Anahita Daruwalla ◽  
Susie Suh ◽  
Henri Leinonen ◽  
Krzysztof Palczewski
Keyword(s):  
G Protein ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Light Sensitivity ◽  
Visual Signal ◽  
Enzymatic Reactions ◽  
Visual Cycle ◽  
Retinal Regeneration ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Driven by the energy of a photon, the visual pigments in rod and cone photoreceptor cells isomerize 11-cis-retinal to the all-trans configuration. This photochemical reaction initiates the signal transduction pathway that eventually leads to the transmission of a visual signal to the brain and leaves the opsins insensitive to further light stimulation. For the eye to restore light sensitivity, opsins require recharging with 11-cis-retinal. This trans–cis back conversion is achieved through a series of enzymatic reactions composing the retinoid (visual) cycle. Although it is evident that the classical retinoid cycle is critical for vision, the existence of an adjunct pathway for 11-cis-retinal regeneration has been debated for many years. Retinal pigment epithelium (RPE)–retinal G protein-coupled receptor (RGR) has been identified previously as a mammalian retinaldehyde photoisomerase homologous to retinochrome found in invertebrates. Using pharmacological, genetic, and biochemical approaches, researchers have now established the physiological relevance of the RGR in 11-cis-retinal regeneration. The photoisomerase activity of RGR in the RPE and Müller glia explains how the eye can remain responsive in daylight. In this review, we will focus on retinoid metabolism in the eye and visual chromophore regeneration mediated by RGR.  

Progressive protein aggregation in PRPF31 patient retinal pigment epithelium cells: the mechanism and its reversal through activation of autophagy

2021 ◽  
Author(s):  
Maria Georgiou ◽  
Chunbo Yang ◽  
Robert Atkinson ◽  
Kuan-Ting Pan ◽  
Adriana Buskin ◽  
...  
Keyword(s):  
Waste Disposal ◽  
Cell Function ◽  
Core Protein ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Cell ◽  
Visual Cycle ◽  
Nuclear Speckles ◽  
Retinal Cells ◽  
Rpe Cells

Mutations in pre-mRNA processing factor 31 (PRPF31), a core protein of the spliceosomal tri-snRNP complex, cause autosomal-dominant retinitis pigmentosa (adRP). It has remained an enigma why mutations in ubiquitously expressed tri-snRNP proteins result in retina-specific disorders, and so far, the underlying mechanism of splicing factors-related RP is poorly understood. Here, we used iPSC technology to generate retinal organoids and RPE models from three patients with severe and very severe PRPF31-adRP, normal individuals and a CRISPR/Cas9-corrected isogenic control. To fully assess the impacts of PRPF31 mutations, quantitative proteomics analyses of retinal organoids and RPE cells was carried out showing RNA splicing, autophagy and lysosome, unfolded protein response (UPR) and visual cycle-related pathways to be significantly affected. Strikingly, the patient-derived RPE and retinal cells were characterised by the presence of large amounts of cytoplasmic aggregates containing the mutant PRPF31 and misfolded, ubiquitin-conjugated proteins including key visual cycle proteins, which accumulated progressively with time. Mutant PRPF31 variant was not incorporated into splicing complexes, but reduction of PRPF31 wildtype levels led to tri-snRNP assembly defects in Cajal bodies of PRPF31 patient retinal cells with reduced U4/U6 snRNPs and accumulation of U5, smaller nuclear speckles and reduced formation of active spliceosomes giving rise to global splicing dysregulation. Moreover, the impaired waste disposal mechanisms further exacerbated aggregate formation, and targeting these by activating the autophagy pathway using Rapamycin resulted in reduction of cytoplasmic aggregates and improved cell survival. Our data demonstrate that it is the progressive aggregate accumulation that overburdens the waste disposal machinery rather than direct PRPF31-initiated mis-splicing, and thus relieving the RPE cells from insoluble cytoplasmic aggregates presents a novel therapeutic strategy that can be combined with gene therapy studies to fully restore RPE and retinal cell function in PRPF31-adRP patients.

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