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Parth Patel, Jing Zhao, Kathryn E Bollinger, Barbara A Mysona; Functional and morphological differences in old and young Brown Norway rat optic nerves: Implications for glaucoma. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3375.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is the leading cause of irreversible blindness in the world. Two risk factors are elevated intraocular pressure and increased age. The Brown Norway (BN) rat has emerged as an important pre-clinical model to study glaucoma. Here, we investigated changes in ON structure and function with age. We hypothesized that in vivo screening of the visual system would correlate with ON morphology.
Male and female BN rats, 11 (average age 15.5 months) and 11 (average age 2.8 months) were used. Prior to sacrifice, pattern electroretinography (PERG), optokinetic response (OKR), and optical coherence tomography (OCT) were assessed. ONs harvested 1.5 mm posterior to the globe, were fixed (4% paraformaldehyde, 2% glutaraldehyde in 0.1-M sodium cacodylate buffer), postfixed (2% osmium tetroxide), and embedded. Semithin (0.5–1 μm) sections stained with 1% toluidine blue were imaged by light microscopy (63x oil). QuPath software was used for automated analysis of axon numbers, densities, and size distributions, percent gliotic area, and ON cross sectional area. Statistical significance (P<0.05) was determined by two-way ANOVA followed by Sidak’s multiple comparison test or two-tailed Student’s t-test.
Overall, ON axon numbers in old and young rats were not statistically different although young female rats had fewer numbers of detected axons. Old rats had significantly lower axon densities and higher ON cross sectional areas than young rats. Old rats had significantly increased NFL thickness but smaller total retinal thickness than young rats. Old rat axon distributions had more small (0.25 µm) and large (>2 µm) diameter axons than young rats. Functional analyses showed significant increases in N2 wave timing in old rat PERGs. Old and young rats had similar visual acuity assessed by OKR but contrast sensitivity trended lower in old rats. Correlations of axon numbers and densities with PERG, OKR, and OCT parameters did not show significant trends.
Old and young rats have subtle but significant differences in ON structure and function. Lack of correlation between in vivo screening and ON morphology suggest that PERG, OKR, and OCT did not predict variations in axon numbers or axon densities at baseline. Examination of other biochemical markers of aging and neurodegeneration may offer a clearer picture of how age affects the propensity to develop glaucoma.
This is a 2021 ARVO Annual Meeting abstract.
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