by Noelle La Croix, DVM, Dip. ACVO
The complicated anatomy of the eye can be roughly divided into 3 layers: an outer fibrous layer (cornea and sclera), a middle vascular layer (choroid and iris), and an inner neurological layer (retina). Uveitis is defined as inflammation within the middle layer commonly called the uvea (Latin grape). The name probably derives from early anatomists that would remove this small bluish-purple (grape-like) tissue from the human eye. Unfortunately, inflammation of the uvea can lead to a wide spectrum of disease. Uveitis can be acute and self-limiting or act as a progressive syndrome (panuveitis) which can lead to blindness.
The eye is normally an immunoprivileged site. A blood ocular barrier (BOB) physically limits exposure of ocular layers to many proteinaceous antigens. The BOB is mainly composed of a non-pigmented ciliary epithelium and a pigmented retinal epithelium. An endothelial component of tight junctions within iris blood vessels and retinal capillaries also contributes to the BOB.
An antigen that manages to cross the BOB does not typically induce an immune response within the eye. The antigens are tolerated and/or immune responses to them are suppressed largely by T lymphocytes. This process is known as anterior chamber-associated immune deviation (ACAID) and its hallmark is an impairment of delayed-type hypersensitivity (DTH) responses (an antibody-independent T-cell mediated immune response). A number of factors are involved in ACAID. The iris and ciliary body secrete the cytokine TGF-beta which is a T lymphocyte and phagocytic monocyte supressor. The aqueous humor contains anti-proliferative (immunosuppressive) factors including the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) and vasoactive intestinal peptide (VIP). The eye also lacks cortisol-binding globulins (cortisol persists), produces minimal complement-fixing antibodies, and secretes FasL (induces apoptosis of activated lymphocytes). Combined, all these factors limit and supress immune responses by the eye and any ocular inflammation is therefore considered aberrant.
Some antigens (particularly if present in great number) can overcome ACAID and the resultant inflammation is uveitis. There are 3 primary etiologies of uveitis: infectious, neoplastic, and autoimmune/idiopathic.
Infectious uveitis primarily manifests in younger animals. Various infectious organisms (fungi, algae, parasites, protozoa, and bacteria) can sometimes evade an immune reponse and linger within the immunoprivileged eye. For example, large organisms and intracellular bacteria typically require macrophages (which the eye lacks) for clearance from a host. Over time the proliferation of these organisms will overwhelm the ACAID resulting in uveitis. Vascular diseases that alter uveal vasculature, and diseases that grossly modify the immune system (e.g.; FIV or FIP), can also lead to cases of infectious uveitis (Figure 1).
A neoplasm within the uvea can also overwhelm ACAID and cause uveitis. These clusters of large dividing cells tend to secrete novel antigens, cause ocular necroses (releasing other antigens), disrupt the endothelial and epithelial layers of the BOB, and stimulate abnormal vessel growth. The aberrant vasculature can ‘leak’ antigens into the eye bypassing the BOB. Common ocular neoplasias in dogs and cats associated with uveitis include: melanoma, iridociliary tumors (adenocarcinoma, ciliary body adenoma), and metastatic lymphoma. In the dog, other uveitis inducing tumors include: histiocytic sarcoma, melanoma, haemangiosarcoma, osteosarcoma, and mammary adenocarcinoma. In the cat, uveitis is also associated with pulmonary carcinoma, squamous cell carcinoma, and fibrosarcoma.
Sometimes an underlying infectious organism, or cancer, cannot be associated with uveitis. In these cases the uveitis is often the result of autoimmunity. For example, an individual may abnormally recognize a protein as a foreign antigen. A number of dog breeds are predisposed to developing autoimmune disease (lupus, chronic superficial keratitis, hemolytic anemia, etc.) and this is linked to their patterns of MHC expression. In these animals, self antigens are inappropriately presented by their MHC and T lymphocytes are subsequently activated. Similarly, ocular self-antigens may be presented to T lymphocytes of animals predisposed to uveitis. Inappropriately activated T cells will then proliferate, overcome ACAID, and permanently populate uveal tissues. These cases will generally require lifelong treatments to preserve vision.
All forms of uveitis are aberrant and must be controlled to prevent damage of ocular tissues. Even low-grade ocular inflammation can cause pain and obstruct vision. The treatment of uveitis will be the subject of my next article
Noelle La Croix, DVM, Dip. ACVO
Veterinary Medical Center of Long Island
75 Sunrise Highway
West Islip, New York 11795
(631) 587-0800; fax (631) 587-2006
Figure 1: The right eye of a 6 month-old female DSH with FIP associated uveitis. Pigmented keratic precipitates of macrophages are present in the ventral corneal endothelium.