Age-related changes in eye morphology and aqueous humor dynamics in DBA/2J mice using contrast-enhanced ocular MRI

Darragh E. Crosbie; James Keaney; Lawrence C.S. Tam; W. Daniel Stamer; Matthew Campbell; Peter Humphries

doi:10.1016/j.mri.2019.01.016

Age-related changes in eye morphology and aqueous humor dynamics in DBA/2J mice using contrast-enhanced ocular MRI

Darragh E. Crosbie, James Keaney, Lawrence C.S. Tam, W. Daniel Stamer, Matthew Campbell, Peter Humphries

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Purpose: Here, we are testing the hypothesis that dynamic contrast enhanced MRI (DCE-MRI) is a useful approach for non-invasively evaluating age-related changes in aqueous humor outflow and its contribution to elevated intraocular pressure in the DBA/2J model of pigmentary glaucoma. Methods: A rodent-specific 7 T MRI was used to assess eye anatomy (anterior chamber (AC) and vitreous body (VB) morphology, eye size, lens size) and aqueous humor dynamics (via intravenous administration of Gd-DTPA and Gd-BOPTA contrast agents) in C57BL/6 and DBA/2J mice at 3 and 9 months of age. Results: Gd-MRI was used to demonstrate an anterior solute pathway into the mouse AC. Topical latanoprost treatment in C57BL/6J mice reduced Gd-BOPTA accumulation in the AC. Age-related increases in AC area, AC depth and eye size were observed in DBA/2J mice compared to C57BL/6J mice. The rate of Gd-DTPA accumulation and peak Gd-DTPA intensity was lowest in 9-month old DBA/2J mice compared to 3-month old DBA/2J mice and C57BL/6J mice at both ages. Leakage of Gd-DTPA posteriorly into the VB was also observed in 9-month old DBA/2J mice. Conclusions: These studies support the idea that age-related changes in aqueous humor outflow contribute to elevated intraocular pressure (IOP) in the DBA/2J model of pigmentary glaucoma. Gd-MRI is a valuable tool for better understanding of mechanisms and dynamics of aqueous humor circulation in normal and glaucomatous mouse eyes or following topical administration of medicines to reduce IOP.

Original language	English (US)
Pages (from-to)	10-16
Number of pages	7
Journal	Magnetic Resonance Imaging
Volume	59
DOIs	https://doi.org/10.1016/j.mri.2019.01.016
State	Published - Jun 2019
Externally published	Yes

Keywords

Aqueous
Contrast enhanced MRI
Glaucoma
Outflow
Trabecular meshwork
Vitreous

ASJC Scopus subject areas

Biophysics
Biomedical Engineering
Radiology Nuclear Medicine and imaging

Access to Document

10.1016/j.mri.2019.01.016

Cite this

@article{930efe8c2c99462c965e1bda5964bdb0,

title = "Age-related changes in eye morphology and aqueous humor dynamics in DBA/2J mice using contrast-enhanced ocular MRI",

abstract = "Purpose: Here, we are testing the hypothesis that dynamic contrast enhanced MRI (DCE-MRI) is a useful approach for non-invasively evaluating age-related changes in aqueous humor outflow and its contribution to elevated intraocular pressure in the DBA/2J model of pigmentary glaucoma. Methods: A rodent-specific 7 T MRI was used to assess eye anatomy (anterior chamber (AC) and vitreous body (VB) morphology, eye size, lens size) and aqueous humor dynamics (via intravenous administration of Gd-DTPA and Gd-BOPTA contrast agents) in C57BL/6 and DBA/2J mice at 3 and 9 months of age. Results: Gd-MRI was used to demonstrate an anterior solute pathway into the mouse AC. Topical latanoprost treatment in C57BL/6J mice reduced Gd-BOPTA accumulation in the AC. Age-related increases in AC area, AC depth and eye size were observed in DBA/2J mice compared to C57BL/6J mice. The rate of Gd-DTPA accumulation and peak Gd-DTPA intensity was lowest in 9-month old DBA/2J mice compared to 3-month old DBA/2J mice and C57BL/6J mice at both ages. Leakage of Gd-DTPA posteriorly into the VB was also observed in 9-month old DBA/2J mice. Conclusions: These studies support the idea that age-related changes in aqueous humor outflow contribute to elevated intraocular pressure (IOP) in the DBA/2J model of pigmentary glaucoma. Gd-MRI is a valuable tool for better understanding of mechanisms and dynamics of aqueous humor circulation in normal and glaucomatous mouse eyes or following topical administration of medicines to reduce IOP.",

keywords = "Aqueous, Contrast enhanced MRI, Glaucoma, Outflow, Trabecular meshwork, Vitreous",

author = "Crosbie, {Darragh E.} and James Keaney and Tam, {Lawrence C.S.} and {Daniel Stamer}, W. and Matthew Campbell and Peter Humphries",

note = "Funding Information: Work at the Ocular Genetics Unit at the University of Dublin, Trinity College, was supported by the European Research Council ERC-2012-AdG . We thank Rustam Rakhmatullin and Christian Kerskens of Trinity College Institute of Neuroscience for technical work with the MRI scanner. Funding Information: Work at the Ocular Genetics Unit at the University of Dublin, Trinity College, was supported by the European Research Council ERC-2012-AdG. We thank Rustam Rakhmatullin and Christian Kerskens of Trinity College Institute of Neuroscience for technical work with the MRI scanner. Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = jun,

doi = "10.1016/j.mri.2019.01.016",

language = "English (US)",

volume = "59",

pages = "10--16",

journal = "Magnetic Resonance Imaging",

issn = "0730-725X",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Age-related changes in eye morphology and aqueous humor dynamics in DBA/2J mice using contrast-enhanced ocular MRI

AU - Crosbie, Darragh E.

AU - Keaney, James

AU - Tam, Lawrence C.S.

AU - Daniel Stamer, W.

AU - Campbell, Matthew

AU - Humphries, Peter

N1 - Funding Information: Work at the Ocular Genetics Unit at the University of Dublin, Trinity College, was supported by the European Research Council ERC-2012-AdG . We thank Rustam Rakhmatullin and Christian Kerskens of Trinity College Institute of Neuroscience for technical work with the MRI scanner. Funding Information: Work at the Ocular Genetics Unit at the University of Dublin, Trinity College, was supported by the European Research Council ERC-2012-AdG. We thank Rustam Rakhmatullin and Christian Kerskens of Trinity College Institute of Neuroscience for technical work with the MRI scanner. Publisher Copyright: © 2019

PY - 2019/6

Y1 - 2019/6

N2 - Purpose: Here, we are testing the hypothesis that dynamic contrast enhanced MRI (DCE-MRI) is a useful approach for non-invasively evaluating age-related changes in aqueous humor outflow and its contribution to elevated intraocular pressure in the DBA/2J model of pigmentary glaucoma. Methods: A rodent-specific 7 T MRI was used to assess eye anatomy (anterior chamber (AC) and vitreous body (VB) morphology, eye size, lens size) and aqueous humor dynamics (via intravenous administration of Gd-DTPA and Gd-BOPTA contrast agents) in C57BL/6 and DBA/2J mice at 3 and 9 months of age. Results: Gd-MRI was used to demonstrate an anterior solute pathway into the mouse AC. Topical latanoprost treatment in C57BL/6J mice reduced Gd-BOPTA accumulation in the AC. Age-related increases in AC area, AC depth and eye size were observed in DBA/2J mice compared to C57BL/6J mice. The rate of Gd-DTPA accumulation and peak Gd-DTPA intensity was lowest in 9-month old DBA/2J mice compared to 3-month old DBA/2J mice and C57BL/6J mice at both ages. Leakage of Gd-DTPA posteriorly into the VB was also observed in 9-month old DBA/2J mice. Conclusions: These studies support the idea that age-related changes in aqueous humor outflow contribute to elevated intraocular pressure (IOP) in the DBA/2J model of pigmentary glaucoma. Gd-MRI is a valuable tool for better understanding of mechanisms and dynamics of aqueous humor circulation in normal and glaucomatous mouse eyes or following topical administration of medicines to reduce IOP.

AB - Purpose: Here, we are testing the hypothesis that dynamic contrast enhanced MRI (DCE-MRI) is a useful approach for non-invasively evaluating age-related changes in aqueous humor outflow and its contribution to elevated intraocular pressure in the DBA/2J model of pigmentary glaucoma. Methods: A rodent-specific 7 T MRI was used to assess eye anatomy (anterior chamber (AC) and vitreous body (VB) morphology, eye size, lens size) and aqueous humor dynamics (via intravenous administration of Gd-DTPA and Gd-BOPTA contrast agents) in C57BL/6 and DBA/2J mice at 3 and 9 months of age. Results: Gd-MRI was used to demonstrate an anterior solute pathway into the mouse AC. Topical latanoprost treatment in C57BL/6J mice reduced Gd-BOPTA accumulation in the AC. Age-related increases in AC area, AC depth and eye size were observed in DBA/2J mice compared to C57BL/6J mice. The rate of Gd-DTPA accumulation and peak Gd-DTPA intensity was lowest in 9-month old DBA/2J mice compared to 3-month old DBA/2J mice and C57BL/6J mice at both ages. Leakage of Gd-DTPA posteriorly into the VB was also observed in 9-month old DBA/2J mice. Conclusions: These studies support the idea that age-related changes in aqueous humor outflow contribute to elevated intraocular pressure (IOP) in the DBA/2J model of pigmentary glaucoma. Gd-MRI is a valuable tool for better understanding of mechanisms and dynamics of aqueous humor circulation in normal and glaucomatous mouse eyes or following topical administration of medicines to reduce IOP.

KW - Aqueous

KW - Contrast enhanced MRI

KW - Glaucoma

KW - Outflow

KW - Trabecular meshwork

KW - Vitreous

UR - http://www.scopus.com/inward/record.url?scp=85061970277&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061970277&partnerID=8YFLogxK

U2 - 10.1016/j.mri.2019.01.016

DO - 10.1016/j.mri.2019.01.016

M3 - Article

C2 - 30660703

AN - SCOPUS:85061970277

VL - 59

SP - 10

EP - 16

JO - Magnetic Resonance Imaging

JF - Magnetic Resonance Imaging

SN - 0730-725X

ER -

Age-related changes in eye morphology and aqueous humor dynamics in DBA/2J mice using contrast-enhanced ocular MRI

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this