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K-Y Kim, L Yuan, S Vora, S Das, AH Neufeld; Effects of Age and Caloric Restriction on Apoptotic Cell Death in the Ganglion Cell Layer After Transient Retinal Ischemia . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2189.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously demonstrated that old age increases susceptibility and caloric restriction (CR) decreases susceptibility for the loss of retinal ganglion cells (RGCs) following retinal ischemia/reperfusion. We have now determined whether the influences of age and CR are through apoptotic cell death in the ganglion cell layer (GCL) after transient retinal ischemia. Methods: We used rats that were 3 months old, 24 months old, and 24 months old that were raised under CR from 4 months of age. Ischemia/reperfusion was induced by anterior chamber cannulation and elevation of the IOP above systolic blood pressure for 75 minutes. By retrograde labeling of RGCs with Fluoro-Gold and TUNEL staining of retinal flatmounts, TUNEL positive RGCs and displaced amacrine cells (DACs) were counted. Results: Within five days after ischemia, there were significant increases in apoptotic cell death in the GCL in young, old and CR/old animals. At one day after ischemia, there were relatively few TUNEL positive RGCs; however, in the peripheral retina of old animals TUNEL positive RGCs were present. At one and five days after ischemia, the number of TUNEL positive RGCs, demonstrating apoptotic cell death, was significantly greater in old animals than in both young and CR/old animals. The numbers of TUNEL positive RGCs in young and CR/old animals were similar; thus, CR significantly decreased the apoptotic cell death of RGCs in old animals. The apoptotic cell death of DACs was significantly increased in central and peripheral retinas of old animals at one and five days after ischemia. Interestingly, apoptotic cell death of DACs did not occur in young animals. More TUNEL positive DACs in old animals were seen earlier than TUNEL positive RGCs. Apoptotic cell death of DACs was significantly decreased in old animals by CR. Conclusion: Compared to retinas in young animals, neurons of the GCL (RGCs and DACs) in retinas of old animals are more susceptible to cell death by apoptotic mechanisms after retinal ischemia. Caloric restriction in old animals is effectively neuroprotective against these apoptotic mechanisms for both RGCs and DACs in the retina following ischemia/reperfusion.
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