Spontaneous retinopathy in HLA-A29 transgenic mice

Abstract

Humans who have inherited the class I major histocompatibility allele HLA-A29 have a markedly increased relative risk of developing the eye disease termed birdshot chorioretinopathy. This disease affecting adults is characterized by symmetrically scattered, small, cream-colored spots in the fundus associated with retinal vasculopathy and inflammatory signs causing damage to the ocular structures, leading regularly to visual loss. To investigate the role of HLA-A29 in this disease, we introduced the HLA-A29 gene into mice. Aging HLA-A29 transgenic mice spontaneously developed retinopathy, showing a striking resemblance to the HLA-A29-associated chorioretinopathy. These results strongly suggest that HLA-A29 is involved in the pathogenesis of this disease. Elucidation of the role of HLA-A29 should be assisted by this transgenic model.

Figure 1

Schematic depiction of the 4-kb recombinant gene containing HLA-A*2902 cDNA used for microinjection. The probe used for analyzing tail-derived DNA is indicated.

Figure 2

Ocular histopathology of the posterior segment of the eye of aging (12 months) A29-negative and A29-positive mice. (A) Posterior segment of an eye from an A29-negative mouse: v, vitreous; r, retina; p, photoreceptor outer segments of visual cells; arrow, retinal pigmented epithelium; ch, choroid. (B–H) Posterior segments of eyes from A29-positive mice. (B) Retinal vasculitis and perivasculitis with infiltrating inflammatory cells in the vicinity of retinal vessels located near the internal limiting membrane (ilm) of the retina (arrow). (C) Retinal fold with serous exudate and retinal pigmented epithelium migration (arrow) observed in the subretinal space of the retina. (D and E) Inflammatory cell infiltration (thin arrow) at the optic nerve head (on) with choroidal inflammation adjacent to the optic disk (arrow, D) and papillitis (E). (F) Several retinal folds with slightly disorganized photoreceptor cell layer (arrow), retinal pigmented epithelium showing aspects of in situ proliferation (arrowhead), and mobilization in the subretinal space. (G and H) Two aspects of retinal and retinal pigmented epithelium pathology with partial destruction of the photoreceptor cell layer and intense retinal pigmented epithelium migration in the retina (G) to almost complete destruction of the photoreceptor cell layer and subretinal serous detachment (H). Paraffin-embedded were sections stained with hematoxylin, eosin, and safran solutions. (Magnification: A, ×800; B, ×1350; C, ×600; D, ×700; E, ×650; F, ×600; G, ×650; H, ×650.)