This is a continuation of an integrated program designed to elucidate the mechanisms of the homeostasis of normal intraocular fluid composition and aqueous humor dynamics and to determine the role of alterations in intraocular micro-environments - as a result of pathophysiological or pathological changes in the permeability and transport functions of the blood-ocular barriers - in (age-dependent) ocular pathologies. We will continue some of our work initiated previously (such as the role of Prostaglandin and other transport processes in ocular homeostasis), but we will focus on testing and elucidating the implications of a set of hypotheses developed during that grant period. These hypotheses, most of which directly relate to our hypothesis of evolutionary divergence in ocular defense mechanisms, state or imply the following: that in some species, especially rabbits, breakdown of the blood acueous barrier (BAB) represents a sophisticated (autocoid mediated) mechanism for the delivery of clotting (and possibly other) factors for corneal repair; that in species which depend on high visual acuity, BAB breakdown occurs less readily, but fibrinogen and other proteins can enter the anterior chamber by canalicular reflux after corneal penetration; that effective BAB breakdown and canalicular reflux depend on anterior uveal and perilimbal hyperemia, respectively; that irritation-induced hyperemia at either of these sites is mediated by a similar mechanism, and possibly by the same autacoids; that episode(s) of intraocular inflammation can cause long-lasting or permanent changes in the transport properties of the blood ocular barrier and, hence, in the intraocular microenvironment, thereby contributing to such disorders as chronic simple glaucoma, presbyopia, senile cataracts and cystoid macular edema. A better understanding of ocular irritative and inflammatory responses and of species differences in these responses will not only allow the rational selection of applicable animal models for human ocular disorders, but will facilitate the development of surgical and therapeutic approaches to these disorders and the adaptation of these approaches to veterinary ophthalmology. A better understanding of the mechanisms of such responses and their control is clearly required in view of the need for increasingly sophisticated and aggressive means of extending the period of useful vision in an increasingly longevous population.
