The matrix metalloproteinase inhibitor BB-1101 prevents experimental autoimmune uveoretinitis (EAU)

EAU is characterized by breakdown of the blood-retinal barrier and extravas ation of leucocytes into retinal tissue leading to destruction of photorece ptor cells. Matrix metalloproteinases (MMP) have been implicated in traffic king of cells into tissues, but their role in inflammatory eye disease is u nclear. A synthetic MMP inhibitor, BB-1101, was administered subcutaneously , from either day 0 or day 7, to Lewis rats challenged with bovine S-antige n to induce EAU. When given up to day 14, BB-1101 reduced the incidence of disease and delayed the day of onset of clinical disease. When administered from day 7 until day 21, EAU was completely abrogated. A quantitative poly merase chain reaction (PCR) assay showed an increase of both matrilysin (MM P-7), neutrophil collagenase (MMP-8) and macrophage metalloproteinase (MMP- 12) in retinas from EAU animals compared with naive controls. These enzymes are produced by activated leucocytes and act on components of the basement membrane. These results therefore implicate these MMP as integral to the d evelopment of pathology in EAU.