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Abstract #18921 Published in IGR 3-1
Modeling of risk factors for the degeneration of retinal ganglion cells following ischemia/reperfusion in rats: effects of age, caloric restriction, diabetes, pigmentation, and glaucoma
Kawai Si S; Vora S; Das S; Gachie E; Becker B; Neufeld AHFASEB Journal 2001; 28;
The authors have determined whether various risk factors relevant to neural injury in the human central nervous system (CNS) can be modelled in the rat. In a model for CNS injury, they have quantitated the survival of retinal ganglion cells (RGCs) following retinal ischemia/reperfusion. Aging was studied by comparing two-year-old rats with two-month-old rats. Caloric restriction was created by providing food to both young and old animals three days per week for three months; controls had continuous access to food. Diabetes was induced by intravenous injection of streptozotocin; controls were injected with citrate buffer. Rats with chronic, moderately elevated intraocular pressure (IOP) were compared with rats with normal IOP. Albino rats and pigmented rats were compared. In all animals, ischemia/reperfusion was produced unilaterally by elevating IOP above systolic pressure for 75 minutes by using anterior chamber cannulation. Loss of RGCs was determined by retrograde labelling with fluorogold. The number of RGCs decreases with age. The remaining RGCs in old rats in both central and peripheral retina were significantly more susceptible to ischemia/reperfusion compared with young rats. Caloric restriction significantly protected against loss of RGCs in the peripheral retina in both young and old rats. In diabetic rats, RGCs throughout the retina were more susceptible to ischemia/reperfusion compared with control rats. The remaining RGCs in rats with glaucoma (pre-existing chronic, moderately elevated IOP) were more susceptible to ischemia/reperfusion damage. Comparing pigmented and albino rats, the loss of RGCs following ischemia/reperfusion did not differ. These results suggest that aging, diabetes, and glaucoma are risk factors for the loss of RGCs following ischemic damage of the retina and can be modelled in rats. Furthermore, reducing caloric intake appears to be neuroprotective for ischemic damage of the retina at all ages. The underlying cellular and molecular factors that are responsible for these risk factors can be studied by using these expanded models of neural injury.
Classification:
1.3 Pathogenesis (Part of: 1 General aspects)
