Comparison of Retinal Nerve Fiber Layer Thickness In Vivo and Axonal Transport after Chronic Intraocular Pressure Elevation in Young versus Older Rats

Purpose: To compare in young and old rats longitudinal measurements of retinal nerve fiber layer thickness (RNFLT) and axonal transport 3-weeks after chronic IOP elevation. Method: IOP was elevated unilaterally in 2- and 9.5-month-old Brown-Norway rats by intracameral injections of magnetic microbeads. RNFLT was measured by spectral domain optical coherence tomography. Anterograde axonal transport was assessed from confocal scanning laser ophthalmolscopy of superior colliculi (SC) after bilateral intravitreal injections of cholera toxin-B-488. Optic nerve sections were graded for damage. Results: Mean IOP was elevated in both groups (young 37, old 38 mmHg, p=0.95). RNFL in young rats exhibited 10% thickening at 1-week (50.9 +/- 8.1 mm, p<0.05) vs. baseline (46.4 +/- 2.4 mu m), then 7% thinning at 2-weeks (43.0 +/- 7.2 mu m, p>0.05) and 3-weeks (43.5 +/- 4.4 mu m, p>0.05), representing 20% loss of dynamic range. RNFLT in old rats showed no significant change at 1-week (44.9 +/- 4.1 mu m) vs. baseline (49.2 +/- 5.3 mm), but progression to 22% thinning at 2-weeks (38.0 +/- 3.7 mu m, p<0.01) and 3-weeks (40.0 +/- 6.6 mu m, p<0.05), representing 59% loss of dynamic range. Relative SC fluorescence intensity was reduced in both groups (p<0.001), representing 77-80% loss of dynamic range and a severe transport deficit. Optic nerves showed 75-95% damage (p<0.001). There was greater RNFL thinning in old rats (p<0.05), despite equivalent IOP insult, transport deficit and nerve damage between age groups (all p>0.05). Conclusion: Chronic IOP elevation resulted in severely disrupted axonal transport and optic nerve axon damage in all rats, associated with mild RNFL loss in young rats but a moderate RNFL loss in old rats despite the similar IOP insult. Hence, the glaucomatous injury response within the RNFL depends on age.