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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
Author(s) -
Kawai Shin-ichiro,
Vora Smita,
Das Sucharita,
Gachie Elizabeth,
Becker Bernard,
Neufeld Arthur H.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0666fje
Subject(s) - medicine , glaucoma , degeneration (medical) , diabetes mellitus , ischemia , ophthalmology , caloric theory , retinal ganglion cell , ganglion , retinal , endocrinology , anatomy
We have determined whether various risk factors relevant to neural injury in the human central nervous system (CNS) can be modeled in the rat. In a model for CNS injury, we have quantitated the survival of retinal ganglion cells (RGCs) following retinal ischemia/reperfusion. Aging was studied by comparing 2‐year‐old rats with 2‐month‐old rats. Caloric restriction was created by providing food to both young and old animals three days per week for 3 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 labeling 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 (preexisting 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. Our results suggest that aging, diabetes, and glaucoma are risk factors for the loss of RGCs following ischemic damage of the retina and can be modeled 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.