Potentially detrimental ocular inflammation has long been known to result from any one numerous insults to the eye, although many of the exact mechanisms involved in the regulation of such immune responses have remained elusive. The proposed studies will examine one facet of the complex controls of these responses by testing the hypothesis that hyaluronic acid can combine with certain proteins of the vitreous to alter their presentation as potential immunogens; this work will especially focus on the expression of auto-allergin or """"""""self"""""""" antigens known to be present in the vitreous from a number of adjacent tissues. These experiments are based on our observations that hyaluronate in biological fluids and in laboratory mixtures can bind to proteins and consequently alter their electrophoretic mobility, as well as their expression as antigens and immunogens. The proposed research program is also supported by recent reports on the interactions between hyaluronate (and other glycosaminoglycans) and certain tissue components including protein antigens and elements of humoral and cell-mediated immune responses. The work outlined here will enhance our understanding both the physiological conditions necessary for the development of protein-polysaccharide complexes in the vitreous, and of the biological role that such binding interactions play in ocular health and disease. To accomplish these aims, antibody probes will be developed against vitreal proteins to to used in highly sensitive immunological tests for the study of hyaluronate-mediated interactions. The in vivo responses to these complexes will also be examined following inoculation of glycosaminoglycan and protein moieties into test animals, as well as by observing alterations in the vitreous in a uveitis-like model (using an animal system which develops massive spontaneous autoimmune disorders). Collectively, the proposed research will fill part of a critical need for additional basic science knowledge of the mechanisms which maintain vitreous body homeostasis. This need is particularly evident now, with an acute clinical interest in developing improved methods for effectively treating that vitreous which has been compromised either directly through disease or indirectly through the treatment of such disorders.
