In vivo assessment of aqueous humor dynamics upon chronic ocular hypertension and hypotensive drug treatment using gadolinium-enhanced MRI.
OBJECTIVE
Although glaucoma treatments alter aqueous humor (AH) dynamics to lower intraocular pressure, the regulatory mechanisms of AH circulation and their contributions to the pathogenesis of ocular hypertension and glaucoma remain unclear. We hypothesized that gadolinium-enhanced magnetic resonance imaging (Gd-MRI) can visualize and assess AH dynamics upon sustained intraocular pressure elevation and pharmacologic interventions.


METHODS
Gadolinium contrast agent was systemically administered to adult rats to mimic soluble AH components entering the anterior chamber (AC) via blood-aqueous barrier. Dynamic Gd-MRI was applied to examine the signal enhancement in AC and vitreous body upon microbead-induced ocular hypertension and unilateral topical applications of latanoprost, timolol maleate, and brimonidine tartrate to healthy eyes.


RESULTS
Gadolinium signal time courses in microbead-induced hypertensive eyes possessed faster initial gadolinium uptake and higher peak signals in AC than control eyes, reflective of reduced gadolinium clearance upon microbead occlusion. Opposite trends were observed in latanoprost- and timolol-treated eyes, indicative of their respective drug actions on increased uveoscleral outflow and reduced AH production. The slowest initial gadolinium uptake but strongest peak signals were found in AC of both brimonidine-treated and untreated fellow eyes. These findings drew attention to the systemic effects of topical hypotensive drug treatment. Gadolinium leaked into the vitreous of microbead-induced hypertensive eyes and brimonidine-treated and untreated fellow eyes, suggestive of a compromise of aqueous-vitreous or blood-ocular barrier integrity.


CONCLUSIONS
Gadolinium-enhanced MRI allows spatiotemporal and quantitative evaluation of altered AH dynamics and ocular tissue permeability for better understanding the physiological mechanisms of ocular hypertension and the efficacy of antiglaucoma drug treatments.
NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Leon C
LC
Ho
UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States Louis J. Fox Center for Vision Restoration, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Ian P
IP
Conner
School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
Chi-Wai
CW
Do
NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States Center for Neuroscience Imaging Research, Institute for Basic Science, Department of Biological Science, Sungkyunkwan University, Suwon, Korea Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, Pennsylvania, United States.
Seong-Gi
SG
Kim
Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China.
Ed X
EX
Wu
UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States Louis J. Fox Center for Vision Restoration, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Gadi
G
Wollstein
UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States Louis J. Fox Center for Vision Restoration, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Joel S
JS
Schuman
NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States Louis J. Fox Center for Vision Restoration, University of Pittsburgh, Pittsburgh, Pennsylvania, United States Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, Pennsylvania, United States.
Kevin C
KC
Chan
D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000502:physiology*; D002908:Chronic Disease; D003287:Contrast Media; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D019786:Gadolinium DTPA; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009798:Ocular Hypertension / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
D000959:Antihypertensive Agents; D003287:Contrast Media; D019786:Gadolinium DTPA
aqueous humor dynamics; gadolinium; intraocular pressure; magnetic resonance imaging; ocular tissue permeability