Numerous corneal diseases (e.g. Fuchs' endothelial dystrophy) are associated with the production of a posterior collagen layer (retrocorneal fibrous membrane). These diseases often require ocular surgery and are a major cause of blindness in the United States. It is strongly suspected that the morphological appearance of the posterior collagen layer (PCL) may be concomitant with altered biochemical (collagen) composition. In an effort to shed some light on the pathogenesis of PCL formation, we propose to study normal and diseased human ocular tissues from several points of view. Normal human Descemet's membrane (DM) and abnormal PCL will be isolated in pure form to yield the necessary starting material for the following experiments: a) experimental ultrastructural techniques will be employed to study regional dissimilarities and histo-architectural integrity; b) biochemical identification of collagen types present within the normal DM (an unresolved point in light of recent reports of new "basement membrane-related" collagens) and PCL from various corneal disorders. Special attention will be given to PCL from Fuchs' endothelial dystrophy (without previous surgery) because it is a defined clinical disorder and corneal "buttons" removed from patients showing this disease are most likely to be homogeneous. We will also investigate less homogeneous PCL in other clinical disorders, the most common of which is aphakic corneal edema. Various isolated mammalian (rabbit, bovine, monkey) DM will be used to standardize our experimental techniques. This will provide an important comparative aspect to the study. The utility of each of these models will be evaluated and compared directly to human DM. It is hoped that these studies will provide insight into the nature of DM and DM/PCL complex alterations in corneal diseases. We believe that when the parameters surrounding the pathogenesis of these disorders are more fully understood, the possibility of elucidating their causes will be within reach. This could lead ultimately to positive therapeutic intervention in the progression of the disease.