Uveitis in horses induced by interphotoreceptor retinoid‐binding protein is similar to the spontaneous disease

Abstract

Equine recurrent uveitis (ERU) is an inflammatory eye disease with high similarity to uveitis in man. It is the only spontaneous animal model for uveitis and the most frequent eye disease in horses affecting up to 10% of the population. To further investigate the pathophysiology of ERU we now report the establishment of an inducible uveitis model in horses. An ERU‐like disease was elicited in seven out of seven horses by injection of interphotoreceptor retinoid‐binding protein (IRBP) in complete Freund's adjuvant. Control horses did not develop uveitis. The disease model is characterized by a highly reproducible disease course and recurrent episodes with an identical time course elicited in all horses by repeated IRBP injections. The histology revealed the formation of lymphoid follicle‐like structures in the eyes and an intraocular infiltration dominated by CD3+ lymphocytes, morphological patterns typical for the spontaneous disease. Antigen‐specific T cell proliferation of PBL was monitored prior to clinical uveitis and during disease episodes. An initial T cell response to IRBP‐derived peptides was followed by epitope spreading to S‐antigen‐derived peptides in response to subsequent immunizations. Thus, horse experimental uveitis represents a valuable disease model for comparative studies with the spontaneous disease and the investigation of immunomodulatory therapeutic approaches after onset of the disease.

The outcome of pars plana vitrectomy in horses with equine recurrent uveitis with regard to the presence or absence of intravitreal antibodies against various serovars of Leptospira interrogans

“…While some authors consider ERU to be a purely immune-mediated disease (Hines and Halliwell 1991, Deeg et al 2001, Deeg et al 2002a, Deeg et al 2002b, Deeg et al 2004, Deeg et al 2006a, Deeg et al 2006b, Deeg et al 2007a, Deeg et al 2007b, Deeg et al 2007c, Deeg 2008, Deeg et al 2008, others consider Leptospira to be the cause or at least the triggering factor for ERU (Matthews et al 1987, Brem et al 1998, Wollanke et al 1998, Brem et al 1999, Faber et al 2000, Rohrbach et al 2002, Wollanke 2004a, Wollanke 2004b, Rohrbach et al 2005). …”

Occurrence and severity of equine recurrent uveitis in warmblood horses - A comparative study

“…So kann z.B. durch subkutane Injektion des Autoantigens CRALB (cellular retinaldehyde-binding protein) oder IRBP (interphotoreceptor retinoid-binding protein) Uveitis ausgelöst werden (Deeg et al 2002, Deeg et al 2007, Deeg 2009 ). Im Vergleich zur Verteilung der Geschlechter in der Klinikklientel (35% Wallache, 15% Hengste und 50% Stuten) waren somit die männlichen Tiere signifikant überrepräsen-tiert (p <0,001).…”

“…In diesen Fällen könnten die ERU-Schübe nicht direkt durch diese Antigene bzw. Antikörper, sondern durch die Folgen von immunologischen Reaktionen ausgelöst worden sein, die alternativ diskutiert werden (Deeg et al 2001, Deeg et al 2002, Deeg et al 2007). Grundsätzlich kann für die verschiedenen pathogenetischen Mechanismen eine genetische Prädisposi-tion in Betracht gezogen werden.…”

Identification and Functional Validation of Novel Autoantigens in Equine Uveitis

“…Equine recurrent uveitis (ERU), 1 a spontaneous, T cellmediated disease with high prevalence among horses, serves as a suitable model for human autoimmune uveitis due to the common sharing of at least two different autoantigens, Santigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP), between equine and human uveitis patients (3,4). Furthermore both autoantigens are capable of inducing experimental uveitis in horses (5,6), and in both, peripheral blood-derived, autoaggressive T cells specific for S-Ag and IRBP epitopes have been detected (3,4). In most autoimmune diseases, several autoantigens participate in the pathogenesis (7), and epitope spreading is accountable for disease induction, progression, and inflammatory relapses (8 -12).…”