Novel Localization of Peripherin 2, the Photoreceptor-Specific Retinal Degeneration Slow Protein, in Retinal Pigment Epithelium

Abstract

Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, equine recurrent uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not retina, in ERU. Moreover, peripherin 2 is clearly detectable in healthy RPE due to both phagocytosis and the expression by the RPE cells themselves. Our novel findings are very promising for better understanding the molecular mechanisms taking place on RPE in uveitis.

High‐Salt Enhances the Inflammatory Response by Retina Pigment Epithelium Cells following Lipopolysaccharide Stimulation

“…The retinal pigment epithelium (RPE), situated on the outer side of the retina, is a monolayer of cells connected by tight junctions with important functions for the visual system [ 1 ]. ARPE-19, a spontaneously arising cell line of RPE, has been extensively used in the past decades to investigate the role of this cell layer in the pathogenesis of a number of diseases including age-related macular degeneration (AMD), vitreoretinopathy, and uveitis [ 2 – 5 ]. The major inflammatory cytokines produced by ARPE-19 in response to various stimuli are interleukin-6 (IL-6), interleukin-8 (CXCL8, IL-8), and monocyte chemoattractant protein-1 (CCL2, MCP-1) [ 6 , 7 ].…”

Immunological Insights in Equine Recurrent Uveitis

“…Furthermore, horses with ERU display a distinctly changed RPE membrane protein repertoire in ERU ( 91 ). A significant decrease of peripherin 2, a protein that is associated with membrane fusion processes, in RPE cells of ERU horses is thought to provoke disruption of the cell-to-cell junctions which are physiolocically maintained through these cells ( 92 ), which in turn points to increased permeability of the outer BRB. As also hypothesized for PEDF ( 19 , 20 , 82 ), this might promote integrity loss of the BRB.…”

“…As also hypothesized for PEDF ( 19 , 20 , 82 ), this might promote integrity loss of the BRB. Although loss of barrier function of the BRB and leukocyte infiltration in course of ERU is evident ( 4 , 27 , 91 , 92 ), the exact chronological order of these events is still not completely clear. Integrity loss of the BRB may occur either as an initial process which subsequently facilitates migration of peripheral immune cells into the eye, or as a secondary effect in response to leukocyte recruitment.…”

Characterization of amino acid changes in visual pigment evolution and interaction with associated proteins

“…In any case, some of the experiments carried out with regenerated Rho point to the fact that the presence of chromophore may not be determinant for the interaction. And despite that some authors suggest more prominent interactions of Rho with guanylate cyclase 1 in comparison with Rho and Prph2 (Pearring, Spencer, Lieu, & Arshavsky, 2015), a novel co-localization of Prph2 and Rho in RPE cells also supports the existence of this protein complex (Uhl et al, 2015).…”

“…In this way, the rim region of the disk membrane has a curvature that is facilitated by the presence of Prph2 (Gurevich & Gurevich, 2015) Recent research provided new insights on this protein showing that Prph2 can interact with Rho, while at the same time demonstrated that Rho is also located in the rim region of the disks (Becirovic et al, 2014) despite previous articles that suggested a compartmental Rho distribution (in the centre) and Prph2 (in the rims) of the ROS disks membranes (Buzhynskyy, Salesse, & Scheuring, 2011). Moreover, Prph2 has also been localized in the RPE (Uhl, Amann, Hauck, & Deeg, 2015) 1.4 Visual signal transduction…”