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Carla Abbott, Tiffany Choe, Claude Burgoyne, Brad Fortune; Axonal Transport Deficits Exceed Retinal Nerve Fiber Layer (RNFL) Changes after 3-weeks of Chronic Intraocular Pressure (IOP) Elevation in Young and Old Rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2155.
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© ARVO (1962-2015); The Authors (2016-present)
To assess RNFL thickness (RNFLT) and axonal transport patency 3-weeks after chronic IOP elevation in young and old rats.
Twelve 2-month-old and twelve 9.5-month-old male Brown-Norway rats were used. Procedures were performed under general anesthesia (ketamine, xylazine, acepromazine 55:5:1 mg/kg IM), except tonometry (TonoLab, iCare) which was measured with topical proparacaine only. IOP was elevated unilaterally by intracameral injections of magnetic microbeads (10µm; Corpuscular Inc.) manipulated into the angle with a magnet. Five baseline IOP measures were collected in trained rats then IOP was measured every other day. RNFLT was measured by SDOCT circle scans (Spectralis, Heidelberg Engineering, GmbH) at baseline (N=21) and at days 7 (N=17), 14 (N=16) and 20 (N=14). Anterograde axonal transport (N=22) was assessed at day 21 by determining the post mortem fluorescence intensity of each superior colliculus 24h after bilateral intravitreal injection of 2µl 1% fluorescent cholera toxin subunit-b. Retinas were evaluated by fluorescence microscopy. Two-way ANOVAs with Bonferroni post-tests were performed.
IOP was elevated in experimental eyes (p<0.01) compared to control but there was no difference (p>0.05) between young and old rats (young mean±s.d.: OD 36.5±4.3, OS 19.2±1.2 mmHg; peak: OD 61.2±6.2, OS 22.8±1.1 mmHg; cumulative difference: 345±90 mmHg.days; old mean: OD 37.5±5.3, OS 18.6±1.2 mmHg; peak: OD 61.9±12.1, OS 22.9±0.8 mmHg; cumulative difference: 366±104 mmHg.days). The experimental eye RNFLT exhibited minimal change from baseline in young rats; day 7: +10.3±15.0% (p<0.05), day 14: -7.2±15.4% (p>0.05), day 20: -7.4±11.8% (p>0.05). Mild RNFL thinning from baseline occurred in old rats; day 7: -4.9±5.6% (p>0.05), day 14: -21.8±9.4% (p<0.01), day 20: -21.4±7.6% (p<0.05). Superior colliculus fluorescence intensity was reduced relative to control by equivalent amounts (p>0.05) in both young (51.4±20.8%, p<0.001) and old (51.7±19.9%, p<0.001) rats, representing a 78% transport deficit. In experimental eyes the RNFL was mostly intact by microscopy despite severely reduced transport to the superior colliculus (Fig.).
Chronic IOP elevation for 3-weeks resulted in severely disrupted anterograde axonal transport in all rats associated with minimal RNFL loss in young rats and mild RNFL loss in old rats.
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