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Ruiyi Ren, David Swain, Julia Lai, Haiyan Gong; Reduced Effective Filtration Area in the Trabecular Meshwork of Steroid-induced Ocular Hypertensive Mouse Eyes. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3476. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The active portion of aqueous humor filtration area along the trabecular outflow pathway is termed effective filtration area (EFA) and can be labeled with perfused fluorescent tracers. Our previous study demonstrated an inverse relationship between intraocular pressure (IOP) and EFA in an ocular hypotensive mouse model. We hypothesize that this relationship also exists in ocular hypertensive mouse eyes. This study aims to determine an inverse relationship between IOP and EFA in a steroid-induced ocular hypertensive (SIOH) mouse model, and to investigate what morphological changes are responsible for the reduction of EFA.
Six-week old C57BL/6 mice (N=28) were randomly divided into two groups (n=14 for each group). Each mouse received topical administration of 10μl of either 0.1% dexamethasone (DEX) or saline to both eyes twice daily for 5 weeks. IOP was measured at baseline and weekly after starting treatment. At the endpoint of treatment, one eye of each mouse received anterior chamber injection with 1μl of 20nm fluorescent tracer at 4nl/second. Forty-five minutes were allowed for tracers to penetrate the trabecular meshwork (TM). The eye was then fixed and processed for confocal microscopy to visualize tracer distribution pattern in the TM. EFA in the TM was measured by percent effective filtration length (PEFL= tracer-labeled TM length/total TM length X 100%). Radial and frontal sections from both high tracer and low tracer regions of five randomly selected eyes from each group were processed for electron microscopy.
IOP significantly increased after one week of DEX-treatment (p<0.01) and stayed elevated for the rest of four weeks compared to controls. At the endpoint, mean IOP in DEX-treated eyes was ~4mmHg higher than control eyes (p<0.001). PEFL was significantly reduced in SIOH mouse eyes (n=11) compared to controls (n=8, 50% vs 78%, p<0.001). There was a significant negative correlation between PEFL and IOP (N=19, R2=0.41, p<0.01). Morphological changes associated with EFA reduction in SIOH eyes include the formation of “curly collagen”, and increased continuity and thickness of basement membrane, especially in the low tracer regions.
Our data confirm the inverse relationship between EFA and IOP, suggesting that increased and abnormal extracellular matrix in the TM contributes to the reduction of EFA, thus elevates IOP in SIOH mouse eyes.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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