TY - JOUR
T1 - Age related optic nerve axonal loss in adult Brown Norway rats
AU - Cepurna, William O.
AU - Kayton, Robert J.
AU - Johnson, Elaine C.
AU - Morrison, John C.
N1 - Funding Information:
Supported by NIH grant EY10145, Oregon Research Foundation and unrestricted funds from Research to Prevent Blindness.
PY - 2005/6
Y1 - 2005/6
N2 - The effect of age on the number and morphology of optic nerve axons in adult Brown Norway rats (5-31 months old) (n=29) was examined using transmission electron microscopy (TEM). By manually counting every axon in areas representing 60% of the optic nerve cross-section, we found a significant negative correlation between age and axon count (R2=0·18, P<0·05). However, when the oldest animals were omitted, the relationship was no longer statistically significant. Simultaneously, the proportion of spontaneously degenerating axons increased at an exponential rate (R2=0·79, P<0·05), with significantly more degeneration in the 31-month group than in 5-month-old animals (ANOVA, P<0·05). This study demonstrates, using quantitative TEM methods, that optic nerve axonal numbers are relatively constant throughout the majority of the adult life of the Brown Norway rat, an increasingly popular strain for glaucoma research. Total axonal loss with aging is substantially less than that reported for other strains. The reduction in axonal numbers and the rate of axonal degeneration do not appear significantly altered until the last few months of life, failing to support some studies that have concluded that optic nerve axon loss in adult rats is linear. However, they do agree with other studies in the rat, and a similar study performed in non-human primate eyes, that concluded that aging changes in the optic nerve and retina follow a complex pattern. Therefore, the impact of animal age must be considered when modeling the course and pathophysiology of experimental glaucomatous optic nerve damage in rats.
AB - The effect of age on the number and morphology of optic nerve axons in adult Brown Norway rats (5-31 months old) (n=29) was examined using transmission electron microscopy (TEM). By manually counting every axon in areas representing 60% of the optic nerve cross-section, we found a significant negative correlation between age and axon count (R2=0·18, P<0·05). However, when the oldest animals were omitted, the relationship was no longer statistically significant. Simultaneously, the proportion of spontaneously degenerating axons increased at an exponential rate (R2=0·79, P<0·05), with significantly more degeneration in the 31-month group than in 5-month-old animals (ANOVA, P<0·05). This study demonstrates, using quantitative TEM methods, that optic nerve axonal numbers are relatively constant throughout the majority of the adult life of the Brown Norway rat, an increasingly popular strain for glaucoma research. Total axonal loss with aging is substantially less than that reported for other strains. The reduction in axonal numbers and the rate of axonal degeneration do not appear significantly altered until the last few months of life, failing to support some studies that have concluded that optic nerve axon loss in adult rats is linear. However, they do agree with other studies in the rat, and a similar study performed in non-human primate eyes, that concluded that aging changes in the optic nerve and retina follow a complex pattern. Therefore, the impact of animal age must be considered when modeling the course and pathophysiology of experimental glaucomatous optic nerve damage in rats.
KW - Aging
KW - Axonal transport
KW - Axons
KW - Glaucoma
KW - Neurodegenerative diseases
KW - Optic nerve
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U2 - 10.1016/j.exer.2004.12.021
DO - 10.1016/j.exer.2004.12.021
M3 - Article
C2 - 15939045
AN - SCOPUS:20444419808
SN - 0014-4835
VL - 80
SP - 877
EP - 884
JO - Experimental Eye Research
JF - Experimental Eye Research
IS - 6
ER -