Lately, spontaneous disease models were established in mice through transgenic expression of retinal proteins or neoantigens, partly accompanied by T-cell receptor (TCR) transgenic T cells or by human HLA.
6,7 The clinical features and pathology of these animal models were highly similar between some human conditions and the mouse.
7 Mice transgenic for the IRBP-specific TCR (R161H) with the uveitis-susceptible B10.RIII background spontaneously develop ocular inflammatory disease similar to human autoimmune uveitis.
8 The R161H uveitis model shows a spontaneous early onset of clinical disease with high incidence and a chronic progressive character.
8 Moreover, it is a valuable source for retina-specific T cells for cellular studies.
8 The disease is characterized by inflammation of retina and choroid leading to loss of vision through retinal damage.
8 Additionally, approximately 40% of R161H mice have lymphoid aggregates in the retina.
9 These aggregates develop 1 month after onset of clinical disease and organize to large lymphoid structures.
9 These lymphoid structures fit the criteria of tertiary lymphoid structures, as shown by gene expression studies and immunohistochemical analyses of cellular markers and transcription factors.
9 Interestingly, we also have detected lymphoid follicle-like structures in a high percentage of horses with equine recurrent uveitis (ERU), a naturally developing uveitis model. Prevalence of ERU varies enormously depending on the continent. Whereas in Europe up to 10% of horses suffer from ERU, in the United States up to 25% are affected.
10 Equine recurrent uveitis can develop at any age, but most horses show the first initial uveitis episode between four and six years of age.
11 The disease is accompanied by spontaneously occurring, remitting, and painful inflammation of the inner eye
11 and shares many clinical and pathologic features to the disease in man.
12 Affected horses show blepharospasm, lacrimation, and photophobia as well as periocular swelling, corneal edema, or miosis.
11,13 Formation of a hypopyon due to breakdown of the blood–retinal barrier and resulting immigration of autoreactive T cells into the inner eye is a further symptom of ERU.
14,15 Therapy with anti-inflammatory drugs (steroids) and cell immunosuppressants (cyclosporine) reveals an improvement of clinical symptoms.
14 With increasing number, the inflammatory episodes lead to irreversible damage of intraocular structures.
16 At terminal stage, the inflammatory process leads to blindness of the affected eye due to destruction of retinal architecture or retinal detachment and phthisis bulbi.
13,12 The horse model offers the remarkable possibility to proof pathophysiologic concepts in experimental animals of the same species,
17,18 since pathophysiologic concepts examined in the spontaneous model can be verified experimentally. For example, IRBP-induced uveitis in experimental horses replicates spontaneous ERU in many aspects.
18 In previous studies, lymphoid aggregates in the inner eye were a common finding in horses with experimental, IRBP-induced uveitis.
18 The finding that genuine tertiary lymphoid tissues develop within the retina in R161H mice
9 prompted us to perform in depth immunologic characterization of respective structures detectable in ERU, another valuable spontaneous recurrent uveitis model.