Uveoretinitis in rabbits following immunization with interphotoreceptor retinoid-binding protein

Interphotoreceptor retinoid-binding protein (IRBP) is a glycoprotein found in the interphotoreceptor matrix between the neurosensory retina and the retinal pigment epithelium and is thought to shuttle retinol among cells that border the interphotoreceptor space. Immunization of rabbits with bovine IRBP caused subsequent photoreceptor degeneration, as documented by light- and electron microscopy. Beginning on post-injection day 18, scattered regions had photoreceptor outer segments that were disorganized and shortened or absent. Macrophages were found between the retinal pigment epithelium and neurosensory retina and within choroidal interstitium and blood vessels. Labeling of these cells with a marker specific for monocytic macrophages (RAM11) and absence of labeling with a marker for retinal pigment epithelium (rabbit anti-bovine cellular retinaldehyde-binding protein) suggest that these macrophages were hematogenous in origin. Staining of retinas with fluorescein isothiocyanate (FITC)-conjugated sheep anti-rabbit IgG revealed leakage of rabbit IgG into the interphotoreceptor matrix on and after day 18 in experimental animals but not in controls, suggesting breakdown of the outer blood-retinal barrier. Indirect immunofluorescence with anti-glial fibrillary acidic protein revealed labeling of Müller cells in experimental retinas on and after day 18, but not in control or shorter survival experimental retinas. There were foci of increased cellularity in the choroid on days 18, 26 and 39. From days 26 through 67, the retinal pathology became more widespread. Varying degrees of outer-segment degeneration were present in all parts of the retina and in many areas there was total loss of outer segments and loss of some photoreceptor-cell bodies. The inner retina appeared unaffected in all experimental and control retinas. These results demonstrate that injection of rabbits with bovine IRBP causes retinal photoreceptor degeneration as anti-IRBP titers increase and breakdown of the outer blood-retinal barrier ensues. Further studies will be required to elucidate factor(s) that control accessibility of the neurosensory retina to circulating antibodies against IRBP and other intrinsic retinal proteins.