Disease relevance of PRPH

• Three of five extraskeletal myxoid chondrosarcomas showed strong cytoplasmic reactivity with anti-peripherin [1].
• METHODS: We induced hypoxic corneal edema and measured corneal deswelling (expressed as percent recovery per hour, PRPH, over 7 hours) with a modified optical pachometer in 12 corneas of 8 patients transplanted 7-18 years previously and in 21 normal adult control subjects [2].
• PURPOSE: To understand the pathophysiology of human retinal degenerations caused by mutations in the peripherin/RDS gene [3].
• Identification of a polymorphic missense (G338D) and silent (106V and 121L) mutations within the coding region of the peripherin/RDS gene in a patient with retinitis punctata albescens [4].
• For example, peripherin is expressed in neuroblastomas, GFAP in astrocytomas and neurofilaments in tumors of neuronal origin [5].

High impact information on PRPH

• We show here that isolated peripherin binds selectively to mammalian lamin B under in vitro conditions [6].
• We studied the molecular associations between peripherin (a neuronal, type III intermediate filament subunit) and nuclear lamins [6].
• Other neuronal intermediate filament proteins (alpha-internexin, peripherin) also accumulated in these spheroids [7].
• Co-cultures of odontoblasts with trigeminal neurons indicate a clustering of alpha2 and beta2 sodium channel subunits and, at the sites of cell-cell contact, a co-localization of odontoblasts beta2 subunits with peripherin [8].
• Role of Peripherin/rds in Vertebrate Photoreceptor Architecture and Inherited Retinal Degenerations [9].

Biological context of PRPH

• A novel RDS/peripherin gene mutation associated with diverse macular phenotypes [10].
• To determine which intragenic regions were critical, mice were generated that expressed peripherin transgenes lacking different introns [11].
• Furthermore, a transgene that lacked intron 1 was not expressed in many neurons that contain endogenous peripherin but was activated after injury [11].
• Intron 1 is required for cell type-specific, but not injury-responsive, peripherin gene expression [11].
• Two novel missense mutations in the peripherin/RDS gene in two unrelated French patients with autosomal dominant retinitis pigmentosa [12].

Anatomical context of PRPH

• The absence of CgA immunolabelling implies the presumptive absence of neuroendocrine antigens, while further research is required in order to clarify the involvement of PRP in dental pulp [13].
• Since peripherin is an important protein in the retina stabilizing the photoreceptor discs it is speculated that this protein might also play a structural role in the pineal gland [14].
• METHODS: Serial sections of human intervertebral discs were immunostained for the neuronal markers (neurofilament 200, peripherin, protein gene product 9.5), for the Schwann cell marker (glial fibrillary acidic protein), and for the endothelial cell marker (CD34) [15].
• One gene that is almost exclusively expressed in neurons of the PNS and is activated after nerve injury is the peripherin intermediate filament gene, but little is known about the genomic elements that control either its restricted expression or its response to nerve injury in adult mice [11].
• Peripherin/RDS is a transmembrane glycoprotein expressed in vertebrate photoreceptors [16].

Associations of PRPH with chemical compounds

• RESULTS: The transplanted corneas had significantly decreased PRPH, induced swelling, endothelial permeability to fluorescein, and endothelial cell density compared to the controls, despite a similar estimated open-eye steady-state thickness [2].
• Serotonin was present in trigeminal neurons containing CGRP, a potent vasoactive neuropeptide, peripherin, an intermediate filament present in neurons with unmyelinated axons, neurofilament H, which is present in neurons with myelinated axons, and in neurons binding IB4, a marker of nonpeptidergic nociceptors [17].
• Mutations in the gene for the beta subunit of cyclic GMP phosphodiesterase cause retinal dystrophies in man, mice and dog, and mutations in the gene for the structural protein peripherin/RDS result in a retinal dystrophy in the mouse and a spectrum of differing retinal dystrophies in man [18].
• We observed the ultrastructural features of surviving SGNs and analyzed the peripherin immunoreactivity at 4, 10, or 20 weeks after systemic injection of neomycin in rats [19].
• RESULTS: A proline to arginine mutation in codon 210 of peripherin/RDS was found in all clinically affected individuals [20].

Other interactions of PRPH

• Network antibodies identify nuclear lamin B as a physiological attachment site for peripherin intermediate filaments [6].

Analytical, diagnostic and therapeutic context of PRPH

• The mouse monoclonal antibody ME 101 raised against human peripherin, an intermediate filament protein (IFP) specific to well defined neuronal populations, recognizes all the major classes of vertebrate IFP in immunoblotting assays [21].
• RESULTS: Sequence analysis of the peripherin/RDS gene revealed no mutations [22].
• Immunofluorescence microscopy and western blotting revealed that excess peripherin provokes reduction in levels of hyperphosphorylated NF-H species in DRG neurites [23].
• Serial sections of the ureterovesical junction were investigated by Masson's trichrome, and hematoxylin and eosin histological staining, enzyme immunohistochemistry for alpha-smooth muscle actin and desmin, as well as double immunofluorescence staining using the neuronal marker peripherin and smooth muscle actin [24].
• Here we show using retrograde transport and immunohistochemistry, that the vestibular efferents, like facial motoneurons, contain peripherin [25].

References