Using the hamster eye, we have provided several lines of morphologic and experimental evidence which suggest that the regions of the choroid which overlie the neural retina are segregated from the intraocular and interstitial fluid pools within or surrounding the globe of the eye. We and others have also demonstrated outflow of cerebrosphinal fluid (CSF) from the optic nerve subarachnoid space at its junction with the globe of the eye. Tracer studies suggest that both aqueous humor and CSF have relatively free access to the interstitium of the sciera and periorbital connective tissue, but are blocked from entering the choroidal interstitium. The perichoroidal barriers to such penetration include the cells and tight junctions of the pigmented epithelium internally, two circular zones of compacted uveal tissues located over the ora serrata and optic nerve junction respectively, and an unusual population of tight junctions interconnecting fibroblasts layered in the lamina fusca. We have preliminary evidence that the lamina fusca in primate eyes is even more complex, contains similar tight junctions, and that compact zones exists as well. The objectives of the current proposal are to obtain a detailed fine structural description of these components in primate eyes and to evaluate the apparent perichoroidal barriers utilizing tracer techniques similar to those employed in the hamster model. We will also undertake a detailed freeze-fracture analysis of the interfibroblastic tight junctions in the primate lamina fusca and compact zones. Results will be compared with data from hamster studies which suggest an interesting molecular model of tight junction structure. We will utilize the larger dimensions of primate eyes to attempt direct tracer infusion into the choroidal interstitium; procedures that were not possible in the smaller hamster model. If the above procedures that were not possible in the smaller hamster model. If the above procedures substantiate the presence of a posterior uveal compartment (PUC) similar to that which we have described for the hamster choroid, we will develop a battery of tracers having differing charge properties and radii and apply them in various strategies to both hamster and primate eyes. In this way we will gain more detailed information as to potential barriers to paracellular interstitial flow in the uvea. Such information should bear importantly on an understanding of ocular and CSF outflow dynamics, and a variety of ocular disorders including glaucoma, choroidoretinal detachment, and the various forms of uveitis.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006188-03
Application #
3262258
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1986-03-01
Project End
1989-06-30
Budget Start
1988-03-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033