Immunopathology of uveitis.

Using conventional histological (light and electron microscopic examinations), immunohistological (immunofluorescent and immunoperoxidase), and molecular histological (in situ hybridisation and polymerase chain reaction (PCR) in situ hybridisation) techniques, the immunopathology of uveitis has been studied using inflamed ocular tissue. The findings usually provide helpful information in the diagnosis and therapy of uveitis. The immunopathology of uveitis allows the visualisation of the morphological interaction in the eye at the time the specimen is obtained. This information also helps in the understanding of the immunopathogenesis of ocular inflammation. Three main aspects of pathological examinations are analysed. Firstly, the morphology of the ocular specimen illustrates the lesions and specific localisations within the eye. These include inflammatory exudate in the anterior chamber, known as hypopyon, commonly located at the inferior angle, inflammatory cellular infiltration in the cornea (keratitis), the uvea (focal or diVuse iritis, cyclitis, iridocyclitis, choroiditis), the retina (retinitis), the vitreous (vitritis or abscess), the sclera (scleritis), and inflammation surrounding the lens or its remnants. The following terms indicate certain pathological findings in the eye. Endophthalmitis occurs when ocular inflammation is confined to three or more tissues inside the eye. Panophthalmitis, on the other hand, indicates that ocular inflammation involves all layers of the eye including the sclera. Anterior uveitis is ocular inflammation in the cornea, the iris, and the ciliary body. Posterior uveitis is ocular inflammation in the choroid, the retina, and the vitreous. Panuveitis is ocular inflammation in both anterior and posterior segments of the eye. Secondly, agents that induce inflammation. Biological, chemical, or physical stimuli can induce ocular inflammation. Various infectious micro-organisms including bacteria, viruses, fungi, and parasites are capable of triggering diVerent degrees of inflammatory response. Several ocular proteins, such as retinal soluble antigen (S-Ag), interphotoreceptor retinoid binding protein (IRBP), and uveal melanin associated proteins, are autoantigens inside the eye. These potent antigens are known not only to induce ocular inflammation in various animal models, but also may be involved in human uveitides based on clinical studies. Cellular responses to S-Ag, IRBP, and their peptides have been reported in patients with uveitis. Antiretinal autoantibodies have been shown in the sera of uveitic patients. 15 Some investigators have considered that sympathetic ophthalmia and Vogt–Koyanagi–Harada (VKH) syndrome reflect autoimmunity against choroidal melanocytes. Recently, two peptides derived from the human S-Ag have been found to bind eYciently to HLAA29, the predisposing allele for birdshot retinopathy. This finding demonstrates the implication of T cell epitopes from retinal autoantigens in birdshot retinopathy. Trauma and foreign bodies can elicit an inflammatory reaction surrounding the wound and foreign material. Tumours may also initiate an inflammatory response. Thirdly, the inflammatory process involves two types of cellular components—the infiltrating inflammatory cells and the ocular resident cells. The types and subtypes of inflammatory cells are easily identified by routine histology and immunohistochemical stains. 4 These cells release numerous lymphokines, cytokines, immunoglobulins, growth factors, and inflammatory mediators, which can be identified by immunohistochemistry. The messenger RNAs of many cytokines and growth factors can be detected by molecular histological techniques. 2 The ocular resident cells may undergo oedema, damage, necrosis, or proliferation. They also respond by releasing cytokines, growth factors, and altering cellular markers including major histocompatibility complex molecules (MHC class I and II), and adhesion molecules. On examining a specimen, consideration of the clinical presentation of the disease is extremely important. The inflammatory response depends on the host condition. Immunocompromised patients generate less inflammatory reaction than immunocompetent patients. Patients with diabetes mellitus or carcinoma may produce a diVerent inflammatory response. Ocular inflammation can be altered by medical treatment, especially immunosuppressive medication or radiation. The genetic background and family history of the patient will also help clarify the immunopathology of uveitis. Because the inflammatory reaction involves such a dynamic process, there is only a short time to view the disease. The pathology is based on this particular picture for the interpretation of the entire inflammatory process. The situation is like being asked to tell a cartoon story from looking at one drawing. Thus, it is necessary to survey the ophthalmic microenvironment for changes in various ocular components and to properly appreciate how these changes influence each other. 21 Many clinical specimens are obtained from end stage disease, and so they may be of little use for the treatment of individual cases.