Search results for "Retina"
showing 10 items of 864 documents
Efficient gene delivery to photoreceptors using AAV2/rh10 and rescue of the Rho–/– mouse
2015
As gene therapies for various forms of retinal degeneration progress toward human clinical trial, it will be essential to have a repertoire of safe and efficient vectors for gene delivery to the target cells. Recombinant adeno-associated virus (AAV) serotype 2/2 has been shown to be well tolerated in the human retina and has provided efficacy in human patients for some inherited retinal degenerations. In this study, the AAV2/8 and AAV2/rh10 serotypes have been compared as a means of gene delivery to mammalian photoreceptor cells using a photoreceptor specific promoter for transgene expression. Both AAV2/8 and AAV2/rh10 provided rescue of the retinal degeneration present in the rhodopsin kno…
Interaction of the retinoic acid signaling pathway with spicule formation in the marine sponge Suberites domuncula through activation of bone morphog…
2011
Abstract Background The formation of the spicules in siliceous sponges involves the formation of cylinder-like structures in the extraspicular space, composed of the enzyme silicatein and the calcium-dependent lectin. Scope of review Molecular cloning of the cDNAs (carotene dioxygenase, retinal dehydrogenase, and BMB-1 [bone morphogenic protein-1]) from the demosponge Suberites domuncula was performed. These tools were used to understand the retinoid metabolism in the animal by qRT-PCR, immunoblotting and TEM. Major conclusions We demonstrate that silintaphin-2, a silicatein-interacting protein, is processed from a longer-sized 15-kDa precursor to a truncated, shorter-sized 13 kDa calcium-b…
OCT-Angiography evaluation of peripapillary microvascular changes after rhegmatogenous retinal detachment repair
2021
Purpose: To evaluate the radial peripapillary capillary plexus (RPCP) vessel density (VD) and the retinal nerve fiber layer (RNFL) thickness in eyes successfully treated with pars plana vitrectomy for primary rhegmatogenous retinal detachment. Methods: In this cross-sectional multicenter clinical study, eyes with a minimum 12-month follow-up were reexamined. The RPCP VD and RNFL thickness in the rhegmatogenous retinal detachment subfields of the affected eye (study group) were compared with the corresponding areas of the healthy fellow eyes (control group). Results: Fifty-three eyes were included in the study. A significantly lower RPCP VD and RNFL thickness were observed in those subfields…
Combination of Resveratrol with omega-3 fatty acids synergize to counteract VEGF-R pathway in sick retinal pigment epithelium cells mimicking AMD
2015
Purpose The aim of this work is to assess whether RSV (Resveratrol) can act synergistically with omega-3 fatty acids to modulate VEGF (Vascular Endothelial Growth Factor) signaling pathway in order to identify a new and more effective therapy for the treatment of AMD (Age-Related Macular Degeneration). Methods In this study, undifferentiated and differentiated human retinal pigment epithelial cells (ARPE-19) were used. The cells were treated with an omega-3/RSV preparation (Resvega®), or a RSV-free formulation or RSV alone for 24 h. The expression of key proteins in VEGF signaling pathway was evaluated by Western Blotting. Results We observed that the combination omega-3/RSV preparation (Re…
Rhodopsin transport in the membrane of the connecting cilium of mammalian photoreceptor cells
2000
The transport of the photopigment rhodopsin from the inner segment to the photosensitive outer segment of vertebrate photoreceptor cells has been one of the main remaining mysteries in photoreceptor cell biology. Because of the lack of any direct evidence for the pathway through the photoreceptor cilium, alternative extracellular pathways have been proposed. Our primary aim in the present study was to resolve rhodopsin trafficking from the inner to the outer segment. We demonstrate, predominantly by high-sensitive immunoelectron microscopy, that rhodopsin is also densely packed in the membrane of the photoreceptor connecting cilium. Present prominent labeling of rhodopsin in the ciliary mem…
Peripherin-2 couples rhodopsin to the CNG channel in outer segments of rod photoreceptors.
2014
Outer segments (OS) of rod photoreceptors are cellular compartments specialized in the conversion of light into electrical signals. This process relies on the light-triggered change in the intracellular levels of cyclic guanosine monophosphate (cGMP), which in turn controls the activity of cyclic nucleotide-gated (CNG) channels in the rod OS plasma membrane. The rod CNG channel is a macromolecular complex that in its core harbors the ion-conducting CNGA1 and CNGB1a subunits. To identify additional proteins of the complex that interact with the CNGB1a core subunit we applied affinity purification of mouse retinal proteins followed by mass spectrometry. In combination with in vitro and in viv…
Differential expression and interaction with the visual G-protein transducin of centrin isoforms in mammalian photoreceptor cells.
2004
Photoisomerization of rhodopsin activates a heterotrimeric G-protein cascade leading to closure of cGMP-gated channels and hyperpolarization of photoreceptor cells. Massive translocation of the visual G-protein transducin, Gt, between subcellular compartments contributes to long term adaptation of photoreceptor cells. Ca(2+)-triggered assembly of a centrin-transducin complex in the connecting cilium of photoreceptor cells may regulate these transducin translocations. Here we demonstrate expression of all four known, closely related centrin isoforms in the mammalian retina. Interaction assays revealed binding potential of the four centrin isoforms to Gtbetagamma heterodimers. High affinity b…
Expression and subcellular localization of USH1C/harmonin in the human retina provide insights into pathomechanisms and therapy
2021
AbstractUsher syndrome (USH) is the most common form of hereditary deafness-blindness in humans. USH is a complex genetic disorder, assigned to three clinical subtypes differing in onset, course, and severity, with USH1 being the most severe. Rodent USH1 models do not reflect the ocular phenotype observed in human patients to date; hence, little is known about the pathophysiology of USH1 in the human eye. One of the USH1 genes, USH1C, exhibits extensive alternative splicing and encodes numerous harmonin protein isoforms that function as scaffolds for organizing the USH interactome. RNA-seq analysis of human retinas uncovered harmonin_a1 as the most abundant transcript of USH1C. Bulk RNA-seq…
Usher Syndrome Protein Network Functions in the Retina and their Relation to Other Retinal Ciliopathies
2014
The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically and clinically heterogeneous: 15 chromosomal loci assigned to 3 clinical types, USH1-3. All USH1 and 2 proteins are organized into protein networks by the scaffold proteins harmonin (USH1C), whirlin (USH2D) and SANS (USH1G). This has contributed essentially to our current understanding of the USH protein function in the eye and the ear and explains why defects in proteins of different families cause very similar phenotypes. Ongoing in depth analyses of USH protein networks in the eye indicated cytoskeletal functions as well as roles in molecular transport processes and ciliary…
Molecular basis of human Usher syndrome: deciphering the meshes of the Usher protein network provides insights into the pathomechanisms of the Usher …
2006
Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in man. It is clinically and genetically heterogeneous and at least 12 chromosomal loci are assigned to three clinical USH types, namely USH1A-G, USH2A-C, USH3A (Davenport, S.L.H., Omenn, G.S., 1977. The heterogeneity of Usher syndrome. Vth Int. Conf. Birth Defects, Montreal; Petit, C., 2001. Usher syndrome: from genetics to pathogenesis. Annu. Rev. Genomics Hum. Genet. 2, 271-297). Mutations in USH type 1 genes cause the most severe form of USH. In USH1 patients, congenital deafness is combined with a pre-pubertal onset of retinitis pigmentosa (RP) and severe vestibular dysfunctions. Those with USH2 have moderate to…