Sorbinil Protection of Lens Protein Components and Cell Hydration during Diabetic Cataract Formation

Abstract

Topical application of Sorbinil, a potent aldose reductase inhibitor, preserved lens growth, cell hydration and protein components – alpha, beta and gamma crystallins. The concomitant protective effects of Sorbinil were established on the three lenticular parameters because their quantitation offered a comprehensive index of lens integrity during galactose cataractogenesis. The fused eyelids of the rat neonate provided a natural delivery chamber, an orbital pouch, for topical administration of inhibitor to the treated lens; the contralateral pouch served as an untreated control. Protein preservation was determined by gel filtration chromatography. In galactose-maintained neonates, untreated lenses exhibited only 50% of the normal fraction-II component, whereas Sorbinil treatment maintained 95% of the protein. Likewise, quantitative analysis of scanning electron micrographs indicated that Sorbinil protected lenses against both intra- and extracellular fluid accumulation as determined by measurements of individual fiber cell thickness, density (the number of cells/10 μm cortex), and interdigitation. In addition, Sorbinil-treatment maintained normal growth as evidenced by radius and dry weight measurements. In normal neonates, Sorbinil had no effect on these parameters. These results indicate that changes in lens growth, fiber ultrastructure and protein components respond to aldose reductase inhibition by Sorbinil, thereby diminishing cataractogenesis.

Diminished Proteinuria in Diabetes mellitus by Sorbinil, an Aldose Reductase Inhibitor

“…Then their lenses were examined with a Zeiss slit-lamp biomi croscope and camera system as previously described [4,12]. We have had considerable experience with sorbinil in cataract model systems [2][3][4][5]. In the present study, we employed the lens as an outside reference for the renal data.…”

Reversal of Stage-I Sugar Cataract by Sorbinil, an Aldose Reductase Inhibitor

“…Inc.). Then their lenses were examined with a Zeiss slit-lamp biomicroscope amd camera system as previously described [5]. While the rats were completely anesthetized, the lenses were extracted and the animals were sacrificed with addi tional ether.…”

“…The extracted lenses were fixed in glutaral- dehyde in an isotonic phosphate buffer (pH 7.3) for 24 h at 24 °C, then stored at 4 "C [5]. Following fixa tion.…”

“…The washed lenses were post fixed in a 1 % solution of osmium tetraoxidc for 24 h [14], Then they were washed in buffer with a graded series of acetone, criti cal point dried in a Denton DCP-1, weighed, coated with a thin layer of gold-palladium (60-40%) and viewed with a JEOL scanning microscope (JSM-35). Quantitative methods for fiber hydration (thickness) were obtained from scanning electron micrographs, as previously described [2,5], The analysis of variance was determined for each group by the procedure of Arrnilage [ 1].…”

“…If aldose reductase is responsible for initiating the opacification, inhibition of this enzyme rep resents a therapeutic approach to modify the course of cataractogenesis. Previous investi gations with aldose reductase inhibitors have employed either in vitro systems [6,12,23] or in vivo systems designed to inhibit the onset of cataractogenesis [4,5,7,10,16]. However, aldose reductase inhibitors may also regulate cataractogenesis subsequent to various stages of cataract formation.…”