Experimental Autoimmune Uveoretinitis in the Rat and Mouse

Experimental autoimmune uveoretinitis (EAU) in rats and mice is a prototypic T cellmediated 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 model. It can be elicited by peripheral immunization with a number of purified retinal proteins or peptides derived from them (uveitogens) in adjuvant, or by adoptive transfer of lymphocytes specific to these antigens. The hallmarks of EAU are onset of ocular inflammation, disruption of the retinal architecture, and partial to complete destruction of the photoreceptor cell layer. The type, number, and size of lesions serve as a basis for a semiquantitative grading system used to score disease severity. A degree of familiarity with ocular histology, or initially the help of an ophthalmic pathologist, is needed to grade the disease in a specific fashion according to the criteria described in Tables 15.6.3, 15.6.4, 15.6.6, and 15.6.7. In practice, disease scores assigned by different observers will not always be identical; however, grading should be consistent when performed by the same person.

In the protocols described here, EAU is induced in rats (see Basic Protocol 1) and in mice (see Basic Protocol 2) by immunization with uveitogenic peptide antigens emulsified in complete Freund's adjuvant (CFA) either by mixing (see Support Protocol 1) or by sonication (see Support Protocol 2). In the Lewis rat, the disease typically takes an acute, monophasic course. Clinical onset can be observed by external examination of the eyes with a flashlight, because the front part of the eye is typically visibly involved. Another approach to monitoring onset of disease involves microscopic examination of the retina, or fundoscopy (see Support Protocol 3). Histopathological lesions are typically diffuse rather than focal; tissue sections of affected eyes are prepared for microscopic analysis (see Support Protocol 4). EAU can also be induced in the rat by adoptive transfer of lymphocytes from uveitic rats (see Alternate Protocol 1) or mice (see Alternate Protocol 2) into unimmunized recipients, which obviates the use of CFA. The typical appearance of clinical and histological disease in the rat is shown in Figures 15.6.1 and 15.6.2.

Table 15.6.1 Susceptibility of Some Inbred Rat Strains to EAUa-b

Strain

MHCC

Susceptibility

Antigenc

Reference

Lewis

RT11

High

S-Ag, IRBP

Caspi et al. (1992b); Gery

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