Disease relevance of Opn5

• These studies clearly show that activation of sensory transduction by unliganded opsin, and not the accumulation of retinyl esters, causes light-independent retinal degeneration in LCA [1].
• Restoration of light sensitivity to the bleached opsin requires chemical regeneration of 11-cis-retinaldehyde through an enzymatic pathway called the visual cycle [2].
• Spontaneous activity of opsin apoprotein is a cause of Leber congenital amaurosis [1].
• Degeneration of photoreceptors in a retinal disease, retinitis pigmentosa, can be caused by the introduction of a mutated opsin gene into mice [3].
• It inhibits granulocyte cathepsin G and neuronal neuropsin, and it is thought to protect cells from death caused by ectopic release or internalization of protease during stress such as infection or cerebral ischemia [4].

Psychiatry related information on Opn5

• The results suggest that generation of reactive oxygen species has an important role in neuropsin transcript in the limbic areas which might be related to the disturbance in avoidance learning [5].

High impact information on Opn5

• Mutations in Rpe65 disrupt synthesis of the opsin chromophore ligand 11-cis-retinal and cause Leber congenital amaurosis (LCA), a severe, early-onset retinal dystrophy [1].
• During visual excitation, rhodopsin undergoes photoactivation and bleaches to opsin and all-trans-retinal [6].
• The mechanisms that control which opsin is expressed in a particular cone are poorly understood, but previous in vitro studies implicated thyroid hormone in cone differentiation [7].
• Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors [8].
• Other membrane, organelle, and transport markers, as well as opsin processing appeared normal [8].

Chemical compound and disease context of Opn5

• Light sensitivity of the opsin pigment is restored through a multistep pathway called the visual cycle, which effects all-trans to 11-cis re-isomerization of the retinoid chromophore [9].
• Extracellular serine protease neuropsin (KLK8) modulates neurite outgrowth and fasciculation of mouse hippocampal neurons in culture [10].

Biological context of Opn5

• Neuropsin comprises seven exons on mouse chromosome 17 [11].
• These animals should provide a useful genetic background on which to express other mutant opsin transgenes, as well as a model to assess the therapeutic potential of re-introducing functional rhodopsin genes into degenerating retinal tissues [12].
• Delayed dark adaptation is likely due to accumulation in discs of the noncovalent complex between opsin and all-trans-RAL [13].
• To study the effect of the specificity of the promoter, we replaced the mouse opsin promoter in MOT1 by a 1.3-kb promoter fragment of the human IRBP gene which is expressed in both rod and cone photoreceptors during embryonic development [14].
• Constitutive activation of phototransduction by K296E opsin is not a cause of photoreceptor degeneration [15].

Anatomical context of Opn5

• Mutations in rod opsin, the visual pigment protein of rod photoreceptors, account for approximately 15% of all inherited human retinal degenerations [16].
• Retinas in mice lacking both opsin alleles initially developed normally, except that rod outer segments failed to form [16].
• Using a proximal murine rod opsin promoter (+86 to -385) to drive expression, reporter gene product was found exclusively in photoreceptors, not in any other retinal cell type or in the adjacent retinal pigment epithelium [17].
• To establish a transgenic mouse line that carries a mutated mouse opsin gene in addition to the endogenous opsin gene, we introduced a mouse opsin gene containing mutations in exon 1 into the germ line of a normal mouse [18].
• These findings provide the first direct evidence that opsin travels along the connecting cilium en route to the outer segment [19].

Associations of Opn5 with chemical compounds

• An action spectrum for the PLR in rd/rd cl mice demonstrates that over the range 420-625 nm, this response is driven by a single opsin/vitamin A-based photopigment with peak sensitivity around 479 nm (opsin photopigment/OP479) [20].
• These data, in conjunction with the established role of CRY2 in photoperiodism in plants, lead us to propose that mammals have a vitamin A-based photopigment (opsin) for vision and a vitamin B2-based pigment (cryptochrome) for entrainment of the circadian clock [21].
• Neuropsin is a novel serine protease, the expression of which is highly localized in the limbic areas of the mouse brain and which is suggested to be involved in kindling epileptogenesis and hippocampal plasticity [22].
• Serine proteinase inhibitor 3 and murinoglobulin I are potent inhibitors of neuropsin in adult mouse brain [23].
• After preincubation of the isolated retina with 9-cis-retinal, neonatal mouse rods showed the same sensitivity as adult rods, suggesting the presence of a small amount of free opsin being responsible for their lower sensitivity [24].

Physical interactions of Opn5

• We found evidence that myosin VIIa functions in the connecting cilium of each photoreceptor cell and participates in the transport of opsin through this structure [19].

Enzymatic interactions of Opn5

• Effects of fibronectin cleaved by neuropsin on cell adhesion and migration [25].

Co-localisations of Opn5

• Also, WOX1 colocalized with fragments of opsin-positive cones [26].

Regulatory relationships of Opn5

• Together, it was suggested that the expression of neuropsin in the brain is regulated entirely by Serpinb6 [27].
• Nevertheless, the mutant opsin constitutively activates transducin in vitro and causes photoreceptor degeneration in vivo, possibly by continuously activating the phototransduction cascade, analogous to constant exposure to environmental light [15].
• The question of whether the expression of mutant opsin predisposes the retina to light damage was addressed using transgenic mice that express rhodopsin with three point mutations near the N-terminus of the molecule [28].
• In Boyden chamber chemotaxis assays, the fibronectin-induced migration of alpha5B2 cells was not affected by neuropsin treatment [25].

Other interactions of Opn5

• Rhodopsin and opsin form structural dimers that are organized in paracrystalline arrays [29].
• METHODS: An RPGRIP expression cassette, driven by a mouse opsin promoter, was packaged into recombinant adeno-associated virus (AAV) [30].
• We can preclude retinal contamination of RPE extracts as levels of Opn4 expression were higher in the RPE than in the retina, and the expression of rod opsin and Thy1 (a marker of the RGC layer) were barely detectable in RPE extracts [31].
• With regards to photoreceptors, NSE and SYN immunoreactive cones were seen in transplants from 14-16 weeks of age, but cone opsin immunoreactivity was not seen until 25 weeks [32].
• Second, the role of IRBP gene and protein expression in development was assessed by determining if their expression occurs before that of opsin [33].

Analytical, diagnostic and therapeutic context of Opn5

• Northern and in situ hybridization analyses demonstrated that neuropsin mRNA is expressed specifically in the limbic system of mouse brain and is localized at highest concentration in pyramidal neurons of the hippocampal CA1-3 subfields [34].
• Opsin was localized in the mutant photoreceptors by immunoelectron microscopy of LR gold-embedded retinas using anti-opsin and antibody gold conjugates [35].
• The rate of opsin synthesis in isolated retinas was measured by 35S-methionine incorporation in vitro, followed by analysis of the radiolabeled opsin by SDS-gel electrophoresis and autoradiography [35].
• Chromatin immunoprecipitation showed that the rod opsin and beta-PDE promoters are targets of both Sp4 and Crx, which further supports Sp4-Crx interactions in vivo in the context of retinal chromatin environment [36].
• Here, we have determined by atomic force microscopy the organization of rhodopsin in native membranes obtained from wild-type mouse photoreceptors and opsin isolated from photoreceptors of Rpe65-/- mutant mice, which do not produce the chromophore 11-cis-retinal [29].

References