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Biomedical subjects

Y Akagi

Publications and source records attributed to Y Akagi.

At least 127 records · Page 7Linked to original sources
PubMed1987

Immunohistochemical localization for aldose reductase in diabetic lenses.

Sugar cataract formation has been demonstrated to result from lenticular sorbitol accumulation. In the lens, the activity of aldose reductase has been observed to increase with the onset of diabetes, while the activity of sorbitol dehydrogenase decreases. This shift in activities of these two Sorbitol Pathway enzymes favors the increased accumulation of sorbitol. Immunohistochemical studies with antibodies prepared against purified rat lens aldose reductase reveal a striking increase in immunoreactive positive staining for aldose reductase in lenses from diabetic rats. Two weeks after the onset of diabetes, increased immunohistochemical staining for aldose reductase appears beneath the epithelial region where water cleft formation occurs, and the intensity of this staining increases with the formation of vacuoles. By 6-8 weeks, the presence of large vacuoles and areas of liquifaction containing dense immunoreactive stain can be observed. Examination of human cataractous lenses with antibodies prepared against purified human placenta aldose reductase suggest similar increases in immunoreactive staining in the human diabetic lens. Cataractous lenses from diabetic patients revealed increased immunoreactive staining for aldose reductase, which was associated with the presence of vacuoles in both the anterior or posterior superficial cortical layers. Examination of similar vacuole containing regions from non-diabetic cataractous lenses revealed no increase in immunoreactive staining for aldose reductase. These results suggest that the enhanced activity of aldose reductase observed in diabetes is due to an increased amount of enzyme, rather than enzyme activation.

Aged↗
PubMed1986

The effect of aldose reductase and its inhibition on sugar cataract formation.

Cataracts associated with diabetes and galactosemia are characterized by their rapid onset and bilateral appearance. These cataracts display similar morphology and histology and have common biochemical mechanisms initiating the cataractous processes. An understanding of these biochemical mechanisms have been aided both by the ability to reproduce these cataracts in various animal models and by the development of potent inhibitors of aldose reductase. This is a US government work. There are no restrictions on its use.

Aldehyde Reductase↗
PubMed1986

Prevention of basement membrane thickening in retinal capillaries by a novel inhibitor of aldose reductase, tolrestat.

A diabetic-like thickening of retinal capillary basement membranes induced in rats fed for 207 consecutive days a diet containing 50% galactose was prevented by the addition to the diet of tolrestat, a potent, structurally novel inhibitor of aldose reductase. Analysis of electron micrographs (X 25,000) of capillaries from the outer plexiform layer of the retina by computer planimetry showed that the basement membranes were approximately twofold thicker in rats fed galactose than in those fed either a standard diet or a diet containing galactose and tolrestat in doses of 43 or 57 mg/kg/day. The thickening of basement membranes in galactose-fed rats was accompanied by other ultrastructural alterations mimicking changes typical of diabetic microangiopathy, such as multilamination and the formation of vacuoles and dense inclusions. Therefore, the galactosemic rat represents a useful model for studying basement membrane-related complications of diabetes and their possible prevention by aldose reductase inhibitors.

Aldehyde Reductase↗
PubMed1986

Aldose reductase localization in dog retinal mural cells.

The selective degeneration of retinal mural cells, a hallmark of early human diabetic retinopathy, has also been reported to occur in both diabetic and galactose-fed dogs. By employing antibodies raised against purified dog lens aldose reductase the presence of aldose reductase can be immunohistochemically demonstrated in the cytoplasm of mural cells but not endothelial cells of dog retinal vessels isolated by trypsin digestion. This immunohistochemical staining is similar to that observed with isolated human retinal vessels.

Aldehyde Reductase↗