Immunocompetent cells in the anterior segment

Immunity to protect the eye from invading pathogens is an absolute requirement for the preservation of vision. However, immune responses carry their own threat of tissue damage, due chiefly to the participation of non-specific inflammation. Because of its delicate microanatomy, the visual axis is vulnerable to distortion (and resulting blindness) from relatively trivial amounts of intraocular inflammation. Therefore, regulation of expression of immunity in the eye is critical to preservation of vision. Regulation of ocular immunity is one expression of the general phenomenon of regional immunity in which local tissue factors mold immune responses to local purposes. Ocular immune privilege is an extreme example of regional immunity. Immune privilege is an active, rather than a passive, process in which regulatory molecules and cells of the eye modulate both the induction and the expression of immunity to eye-derived antigens. Immune privilege is achieved primarily through unique features of the eye, ranging from special microanatomic factors (blood:eye barrier, absence of lymphatic draining), to soluble factors secreted by ocular cells into the ocular microenvironment, to regulatory molecules constitutively expressed on the surfaces of ocular cells. In general, the most important consequence of regulation of ocular immune responses is the virtual elimination of immunogenic inflammation from the eye. While this enables the eye to receive immune protection without the threat of blinding inflammation, it also renders the eye vulnerable to those pathogens whose elimination requires the participation of inflammatory molecules and cells.

cDNA clones encoding S-antigen (arrestin) were isolated from the expression library constructed from porcine retina and sequenced. The 1490 base pair fragment contained a 1215 base pair open reading frame. From the nucleotide sequence, an amino acid sequence consisting of 405 residues was deduced and a molecular mass of 45102 daltons was calculated. In order to determine whether the S-antigen mRNA transcript was expressed in anterior eye tissues, mRNA from ciliary non-pigmented epithelial cells and pigmented epithelial cells and iris was analysed by the reverse transcription polymerase chain reaction (PCR) using primers taken from sequences flanking the coding and non-coding regions of retinal S-antigen. Sequence analysis of the expected 611 base pairs in the 5′ region and 672 base pairs in the 3′ region of DNA fragments indicated that an identical mRNA for S-antigen was expressed in the anterior tissues examined. To investigate the in situ expression of S-antigen mRNA,³⁵S-labeled sense and antisense RNA probes were synthesized from the cDNA to label frozen sections of retina, ciliary body and iris and the treated sections were examined by autoradiography. The antisense probe labeled the layer between retinal pigmented epithelium and the outer nuclear layer of the retina, ciliary epithelium, and iris epithelium. From the results of sequencing PCR products and in situ hybridization, we concluded that, in porcine eye, the mRNA for S-antigen is expressed not only in the retina but also in the anterior tissues such as the ciliary epithelium and iris epithelium.

Experimental autoimmune uveitis (EAU), a disease induced in animals immunised at distant sites with retinal antigens, in conjunction with appropriate adjuvants, is a well recognised paradigm of various forms of human uveitis since many of the clinical and histopathological manifestations of the human disease can be closely mimicked in this model. Electron microscopy and other nonultrastructural morphological techniques have proven valuable tools in studying the pathology of EAU due to the highly organised and heterogeneous nature of the affected cells and tissues within the eye, namely the neural retina, retinak pigment epithelium and choroid. The role of various resident ocular immune cells including mast cells, dendritic cells, choroidal macrophages and retinal microglia in the induction and pathogenesis of EAU, is reviewed. In addition, the role of various effector cells in the inflammatory cell infiltrate, namely polymorphonuclear leukocytes, T cells and macrophages, and their interaction with retinal target cells is discussed. This review also considers the morphological changes which precede and accompany early inflammatory cell infiltration through the blood-ocular barrier which are of critical importance to initiation of the autoimmune process. In many ways EAU represents an ideal model for autoimmune diseases in general and especially for those involving the central nervous system. The precise microanatomical arrangement of the eye and its distinct blood-tissue barriers have allowed researchers studying EAU to precisely identify the target cells, pathways used by ingressing inflammatory cells and the nature of the effector cells in this disease.