Purpose: Prominin-1 expresses in rod and cone photoreceptors. Mutations in the prominin-1 gene cause retinal degeneration in humans. In this study, the authors investigated the expression and subcellular localization of xlProminin-1 protein, the Xenopus laevis ortholog of prominin-1, in rod and cone photoreceptors of this frog.
Methods: Antibodies specific for xlProminin-1 were generated. Immunoblotting was used to study the expression and posttranslational processing of xlProminin-1 protein. Immunocytochemical light and electron microscopy and transgenesis were used to study the subcellular distribution of xlProminin-1.
Results: xlProminin-1 is expressed and is subject to posttranslational proteolytic processing in the retina, brain, and kidney. xlProminin-1 is differently expressed and localized in outer segments of rod and cone photoreceptors of X. laevis. Antibodies specific for the N or C termini of xlProminin-1 labeled the open rims of lamellae of cone outer segments (COS) and the open lamellae at the base of rod outer segments (ROS). By contrast, anti-peripherin-2/rds antibody, Xper5A11, labeled the closed rims of cone lamellae adjacent to the ciliary axoneme and the rims of the closed ROS disks. The extent of labeling of the basal ROS by anti-xlProminin-1 antibodies varied with the light cycle in this frog. The entire ROS was also faintly labeled by both antibodies, a result that contrasts with the current notion that prominin-1 localizes only to the basal ROS.
Conclusions: These findings suggest that xlProminin-1 may serve as an anti-fusogenic factor in the regulation of disk morphogenesis and may help to maintain the open lamellar structure of basal ROS and COS disks in X. laevis photoreceptors.
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http://dx.doi.org/10.1167/iovs.11-8635 | DOI Listing |
Cells
January 2025
Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Retinitis pigmentosa (RP) is a hereditary disease characterized by progressive vision loss ultimately leading to blindness. This condition is initiated by mutations in genes expressed in retinal cells, resulting in the degeneration of rod photoreceptors, which is subsequently followed by the loss of cone photoreceptors. Mutations in various genes expressed in the retina are associated with RP.
View Article and Find Full Text PDFCell Syst
December 2024
The Edison Family Center for Genome Sciences & Systems Biology, Saint Louis, MO 63110, USA; Department of Genetics, Saint Louis, MO 63110, USA. Electronic address:
Deep learning is a promising strategy for modeling cis-regulatory elements. However, models trained on genomic sequences often fail to explain why the same transcription factor can activate or repress transcription in different contexts. To address this limitation, we developed an active learning approach to train models that distinguish between enhancers and silencers composed of binding sites for the photoreceptor transcription factor cone-rod homeobox (CRX).
View Article and Find Full Text PDFJ Physiol
January 2025
Department of Ophthalmology, Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA.
Bipolar cells are vertebrate retinal interneurons conveying signals from rod and cone photoreceptors to amacrine and ganglion cells. Bipolar cells are found in all vertebrates and have many structural and molecular affinities with photoreceptors; they probably appeared very early during vertebrate evolution in conjunction with rod and cone progenitors. There are two types of bipolar cells, responding to central illumination with depolarization (ON) or hyperpolarization (OFF).
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology, the First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, USTC, Hefei, China.
Purpose: Oxidative phosphorylation (OXPHOS) is an aerobic metabolic mechanism, and its dysfunction plays an important role in the pathological changes of ischemic diseases. However, systematic studies on the occurrence of retinal detachment (RD) are lacking.
Methods: Single-cell RNA sequencing (scRNA-seq) of the human retina was performed to detect the metabolic changes of various retinal cells after RD.
Eye (Lond)
January 2025
Division of Experimental Retinal Therapies, Department of Clinical Sciences, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA, 19104, USA.
In this review, we summarize the findings of several pre-clinical studies in the canine BEST1 disease model. To this end, client-owned and purpose bred dogs that were compound heterozygotes or homozygotes, respectively, for two or one of 3 different mutations in BEST1 were evaluated by ophthalmic examination, cSLO/sdOCT imaging, and retinal immunohistochemistry to characterize the clinical and microanatomic features of the disease. Subsequently AAV-mediated gene therapy was done to transfer the BEST1 transgene to the RPE under control of a hVMD2 promoter.
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