Abstract
Purpose :
Increased resistance to aqueous humor outflow through conventional outflow tissues is a primary risk factor for glaucoma, however, underlying mechanisms are not fully understood. The majority of outflow resistance occurs where the trabecular meshwork (TM) and inner wall of Schlemm’s canal (SC) interact. Yet, 25-40% of outflow resistance is generated by vessels distal to SC. Phenylephrine (PE), a mydriatic eye drop, is a vasoconstrictor that reduces rabbit conjunctival venous diameter and velocity, and induces IOP fluctuations in humans. The aim of this study was to investigate the effects of PE on outflow tissue morphology and IOP in living mice.
Methods :
Both genders of Balb/c and C57BL/6 mice were used (Duke animal protocol A001-19-01). Anterior ocular tissue behaviors were visualized in living animals by SD-OCT (Bioptigen) in response to topical 1.25% PE alone or with 0.5% tropcamide (trop). Red blood cells (RBCs) in Schlemm’s canal (SC) were visualized in Balb/c mice using bright field microscopy of anterior segment flat mounts. IOP was measured by tonometry (TonoLab). Aqueous humor flow patterns were observed using 0.1µm green fluorescent beads perfused into living eyes and quantified using custom software.
Results :
Average IOP increased post drug treatment (40-120 min) with either topical PE (2.05±0.85 mmHg, n=3) or PE+trop (2.88±0.20 mmHg, n=6). Treatment with either PE or PE+trop appears to cause elevated episcleral venous pressure as indicated by RBC accumulation in SC over 2 quadrants from ~5 to 120 min post drug treatment. Cross-sectional area of SC lumen became smaller ~20 min post PE+trop treatment by 32.2±6.2% (n=3). Meanwhile, a decreased amount of fluorescent beads appeared in outflow tissues 40 min post PE+trop treatment compared to PBS-treated controls. Finally, PE had similar effects in mice to those known to occur in human eyes: a decrease of anterior segment depth, anterior ciliary body motion, and pupillary dilation.
Conclusions :
Phenylephrine induced RBCs accumulation in SC and decreased amount of tracer accumulation in TM, which could be due to PE constricting distal outflow vessels. Interestingly, PE decreased SC lumen area indicating that PE effects on ciliary body and iris may also be involved in the changes of outflow function as pilocarpine does. PE effects on outflow function may be via both conventional and uveal outflow pathways and should be further investigated.
This is a 2021 ARVO Annual Meeting abstract.