An integrated research program is proposed to elucidate the relative roles played by different regions of the blood-ocular barriers and by different compartments of intraocular fluid (IOF) in the homeostasis of normal ocular micro-environments; to identify the factors which affect the permeability and transport properties of these barriers; and to define the effects of altered barrier function on IOF composition and on the functional integrity of intraocular tissues. Among the hypotheses to be tested are the following: that the vitreous plays a major role in maintaing the micro-environment of the retina, especially during acute ischemia, by acting as a reservoir of nutrients and as a sink for metabolic wastes; and that episodes of acute or subclinical ocular inflammation or traumata contribute to the cumulative deterioration of blood-ocular barrier functions. Permeability properties of blood-ocular barriers will be studied in vivo. Normal and altered transport properties (especially with reference to prostaglandin transport) of the tissues primarily associated with these barriers will be studied both in vivo and vitro. The time-course of several models of ocular inflammation will be studied to identify the individual mediators associated with each inflammatory phase whereupon the effects of these mediators on barrier function and IOF composition will be explored. The possibility that deterioration of barrier functions may result in abnormal trace metal concentrations in the IOFs, which may, in turn, contribute to an adverse chemical milieu will also be investigated. The clinical significance of our proposed research becomes apparent in light of increasing evidence that some and possibly most ocular disorders, especially slowly developing degenerative disorders such as simple chronic glaucoma, presbyopia, senile cataract and macular degeneration are caused by or are associated with abnormalities in the ocular micro-environment.
