[Physiology of retinal vessels in acute and chronic changes of blood composition].
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The effects of the long-term oral angiotensin-converting enzyme inhibitor, cilazapril, on retinal circulation in stroke-prone spontaneously hypertensive (SHR-SP) rats were assessed by scanning electron microscopy (SEM), corrosion casts and transmission electron microscopy (TEM). Two groups of 20 male SHR-SP rats were compared. One group was treated with 10 mg/kg/day of cilazapril from 4 to 40 weeks of age, and the other group received no treatment. A third group of male Wistar-Kyoto (WKY) rats served as age-matched controls. At regular intervals the rats were weighed, and their systolic blood pressure was measured. Cilazapril normalized systolic arterial pressure to 121+/-2.7 mm Hg (SD) in the treated SHR-SP rats. There was no significant difference in body weight between the two groups of SHR-SP. In the 40-week-old SHR-SP rats without treatment corrosion cast and SEM revealed hypertensive retinal vascular changes. In the 40-week-old SHR-SP rats treated with cilazapril, these changes were markedly decreased to the level seen in WKY rats. The differences in caliber of retinal capillaries between the treated SHR-SP and untreated SHR-SP rats were statistically significant (p<.0001). TEM in the cilazapril-treated SHR-SP rats revealed intact basement membranes (0.29+/-0.057 microm) of the endothelial cells and pericytes, but in the untreated SHR-SP rats the basement membrane was thickened (0.51+/-0.123 microm) (p<.0001) and the pericytes damaged. Our results show that the long-term administration of cilazapril decreased systolic arterial pressure to a nearly normal level and prevented hypertensive retinal vascular changes, probably by improving endothelial function. The effects of cilazapril on the retinal vasculature are described for the first time. SEM of corrosion casts is a valuable technique for showing the effects of some drugs on the vasculature easily, precisely and three-dimensionally.
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To delineate the factors involved in the pathogenesis of human retinal vasculopathies, as in vitro model of human retinal vascular cells was developed by using cadaver eyes enucleated four to eight hours after death and stored at +4 C for three to seven days. A pure, viable capillary explant was obtained by microdissection and gentle agitation; the more rapidly occurring postmortem changes in the surrounding nervous tissue of the retina facilitated separation of the vascular explants. Factor VIII indirect immunofluorescent staining revealed that 85% to 90% of the cells harvested from capillaries of 3- to 5-day-old cadaver eyes and all cells cultured from 1-week-old postmortem eyes reacted positively, indicating their endothelial nature. High-glucose medium caused degenerative changes in the cells of the initial explant as well as in the cells of confluent cultures within 24 to 72 hours. The cytotoxic effect of glucose was manifested by accumulation of PAS-positive granules, cytoplasmic vacuolation, and eventual cell degeneration.
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