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.

Highlights

  • Autoimmune uveitis is a sight-threatening disease mediated by autoreactive T-cells that cross the blood-retinal barrier with subsequent inflammation of the inner eye and destruction of retinal structures [1]

  • Due to the fact that, to our knowledge, there was no information about the expression pattern of peripherin 2 in equine retina, we were interested in assessing its physiological expression pattern, as well as its disease-associated changes

  • The same expression pattern was found in equine recurrent uveitis (ERU) diseased retinas, where peripherin 2 was localized in the thinner, but still completely intact, photoreceptor outer segments with a similar intensity and distribution (Figure 1F, peripherin 2 = red) as in healthy equine retinas (Figure 1B, peripherin 2 = red)

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Summary

Introduction

Autoimmune uveitis is a sight-threatening disease mediated by autoreactive T-cells that cross the blood-retinal barrier with subsequent inflammation of the inner eye and destruction of retinal structures [1]. The only spontaneous animal model for autoimmune uveitis in man is equine recurrent uveitis (ERU), a remitting-relapsing disease of horses that results in blindness [2,3]. There are many similarities in clinical presentation, the course of the disease and autoimmune reactions between human autoimmune uveitis patients and ERU cases [2,4]. These resemblances and the fact that intraocular tissue samples are available from horses in all stages of disease, which have an outbred genetic background and are exposed to all typical environmental conditions, render ERU an ideal model for uveitis in man. Investigating pathomechanisms contributing to this frequently occurring eye disease of horses has become very important [2,5]

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