Experimental autoimmune uveoretinitis (EAU)
EAU in rats, mice, guinea pigs and monkeys is a prototypic T-cell mediated autoimmune disease that targets the neural retina and related tissues. The model is used to represent human sight-threatening inflammatory eye diseases that are believed to have an autoimmune etiology, and to study basic mechanisms of tolerance and autoimmunity to organ-specific antigens from immunologically privileged sites. EAU is an induced (as opposed to spontaneous) autoimmune disease. It can be elicited by peripheral immunization with one of several uveitogenic retinal proteins (or with peptides derived from them) in adjuvant, or by the adoptive transfer of lymphocytes specific to these antigens. The hallmark of EAU is an intraocular inflammation that leads to disruption of the retinal architecture and partial to complete destruction of the photoreceptor cell layer.
|Photomicrograph of experimental autoimmune
uveoretinitis (EAU) in the B10A mouse
1: retinal folds
As a rule, uveitogenic retinal proteins are evolutionarily well-conserved molecules, whose homologues can be found as far down the phylogenetic scale as the invertebrates. Most of these proteins have also been found in the pineal gland (“third eye”). Consequently, pinealitis is usually induced concurrently with uveitis. The main uveitogenic retinal proteins defined thus far are:
- The retinal soluble antigen (S-Ag, arrestin). This 48 kDa intracellular photoreceptor protein is involved in the phototransduction cascade.
- Interphotoreceptor retinoid-binding protein (IRBP). This 148 kDa protein is found in the interphotoreceptor matrix, and is thought to transport Vitamin A derivatives between the photoreceptor and the retinal pigment epithelium.
- Rhodopsin, and its illuminated form, opsin. This 40 kDa membrane protein is the rod visual pigment
- Recoverin, a 23 kDa calcium-binding protein
- Phosducin, a 33 kDa soluble cytosolic photoreceptor phosphoprotein
All five proteins are uveitogenic in Lewis rats. IRBP is known to be uveitogenic in mice.