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The perfused human anterior segment as a model for aqueous outflow physiology
Friday, Sep 25, 1992 La Palms/A
X ICER Abstracts
THE PERFUSED HUMAN ANTERIOR AQUEOUS OUTFLOW PHYSIOLOGY Alison Schroeder-Bedenkoo, Department of Ophthalmology, Boston, MA
SEGMENT
AS A MODEL
Kristine Harvard
FOR
A. Erickson-LamY Medical School,
The perfused ocular anterior segment is a model system developed on our laboratory to study the effects of drugs and surgical manipulations on conventional aqueous outflow in the human eye. This model involves placement of the eviscerated corneoscleral shell -(with lens and uveal tissue removed but trabecular meshwork (TM) attached) onto a specialized perfusion apparatus with subsequent perfusion with culture medium at a physiologicallyrelevant perfusion pressure in a 5% CO2 environment at 37oc. Measured facility of outflow (O.Z7lul/min/mmHg) is similar to facility values obtained by tonography in living human beings. Moreover, outflow facility decreases in a linear fashion with increased oerfusion oressure bv l.l%/mmHa. Finallv. the kernoval of-the TM results in a-41% decrease in measured outflow resistance. To date we have demonstrated physiological responsiveness to several pharmacological agents including epinephrine, ethacrynic acid, and forskolin. Supported and NE1
in part (EY 07321).
NAQNETIC RESONANCE Chena. Hona-Ming Howe Labor&or-v of School, and Ma&ch&tts 243 Charles Street,
by
Mass.
INAQING
Lions
OP TNE
Eye
Research
AQUEOUS/WATER
Fund
FLOW
Ophthalmoloqv. Harvard Medical Eye and Ear Infirmary, Boston, MA 02114, USA
High-resolution magnetic resonance imaging (MRI) was used to record and quantify aqueous and water movement in the eye, the former in conjunction with topical or intravenous GdDTPA (mol wt: 550), and the latter, topical H2170. The flow rate constants for the aqueous and water in the rabbit eye were 0.01 and o.lO/min, respectively. The principal component of the water flow appeared to be iris circulation. In humans, the non-glaucomatous eye showed a uniform increase in Tl image intensity of the ciliary body and choroid immediately after intravenous GdDTPA injection. In neovascular glaucoma, GdDTPA leaked from iris blood vessels into the anterior chamber and In nanophthalmos the choroid was partially enhanced. with elevated IOP and POAG, only segmental choroidal enhancement was noted. GdDTPA did not enter from the aqueous chamber-ciliary body into the vitreous in all eyes tested. Since all glaucoma cases tested were pseudophakic, the absence of a GdDTPA flow indicates a functional barrier at the anterior vitreous. in the human eye as determined with H2 170 flow TZ-weighted imaging resembled that of the rabbit eye with k=O.lO/min. These results suaaest that MRI potentially is useful for the assessment of the aqueous and water flow in the human eye.
NON-INVASIVE DEUTERIUM MAGNETIC RESONANCE SPECTROSCOPY (2H-MRS) STUDIES OF AQUEOUS HUMOR FORMATION IN THE RABBIT. James A. Wrllisf. Craig E. Crosson? and Y Thomas Schleichl. 1 Dept. of Chemistry and Biochemistry, University of California, Santa Cruz. California, USA and sTexas Tech University Health Sciences Center, Lubboch, Texas, USA. To evaluate the feasibility of using magnetic resonance spectroscopic techniques for the non-invasive measurement of aqueous humor dynamics, we previously demonstrated that aqueous formation in rabbits can be monitored by 2H-MRS (Willis, et al. lsS1). The natural abundance deuterfum signal arising from HDO in the anterior chamber is readily detected using a 7 mm, 2 turn surface coil placed in a co-planar orientation over the cornea. Following i.v. bolus administration of isotonic deuterium oxide (D20) the accumulation of HDO in the anterfor chamber, reflecting aqueous formation, can be readily monitored. Details of the technique and the results of ongoing experiments conducted at 4.7 T examining the feasibility of using this methodology to study pharmacologic regulation of aqueous humor formation in adult New Zealand White rabbits will be presented.
S.214
X ICER Abstracts
THE PERFUSED HUMAN ANTERIOR AQUEOUS OUTFLOW PHYSIOLOGY Alison Schroeder-Bedenkoo, Department of Ophthalmology, Boston, MA
SEGMENT
AS A MODEL
Kristine Harvard
FOR
A. Erickson-LamY Medical School,
The perfused ocular anterior segment is a model system developed on our laboratory to study the effects of drugs and surgical manipulations on conventional aqueous outflow in the human eye. This model involves placement of the eviscerated corneoscleral shell -(with lens and uveal tissue removed but trabecular meshwork (TM) attached) onto a specialized perfusion apparatus with subsequent perfusion with culture medium at a physiologicallyrelevant perfusion pressure in a 5% CO2 environment at 37oc. Measured facility of outflow (O.Z7lul/min/mmHg) is similar to facility values obtained by tonography in living human beings. Moreover, outflow facility decreases in a linear fashion with increased oerfusion oressure bv l.l%/mmHa. Finallv. the kernoval of-the TM results in a-41% decrease in measured outflow resistance. To date we have demonstrated physiological responsiveness to several pharmacological agents including epinephrine, ethacrynic acid, and forskolin. Supported and NE1
in part (EY 07321).
NAQNETIC RESONANCE Chena. Hona-Ming Howe Labor&or-v of School, and Ma&ch&tts 243 Charles Street,
by
Mass.
INAQING
Lions
OP TNE
Eye
Research
AQUEOUS/WATER
Fund
FLOW
Ophthalmoloqv. Harvard Medical Eye and Ear Infirmary, Boston, MA 02114, USA
High-resolution magnetic resonance imaging (MRI) was used to record and quantify aqueous and water movement in the eye, the former in conjunction with topical or intravenous GdDTPA (mol wt: 550), and the latter, topical H2170. The flow rate constants for the aqueous and water in the rabbit eye were 0.01 and o.lO/min, respectively. The principal component of the water flow appeared to be iris circulation. In humans, the non-glaucomatous eye showed a uniform increase in Tl image intensity of the ciliary body and choroid immediately after intravenous GdDTPA injection. In neovascular glaucoma, GdDTPA leaked from iris blood vessels into the anterior chamber and In nanophthalmos the choroid was partially enhanced. with elevated IOP and POAG, only segmental choroidal enhancement was noted. GdDTPA did not enter from the aqueous chamber-ciliary body into the vitreous in all eyes tested. Since all glaucoma cases tested were pseudophakic, the absence of a GdDTPA flow indicates a functional barrier at the anterior vitreous. in the human eye as determined with H2 170 flow TZ-weighted imaging resembled that of the rabbit eye with k=O.lO/min. These results suaaest that MRI potentially is useful for the assessment of the aqueous and water flow in the human eye.
NON-INVASIVE DEUTERIUM MAGNETIC RESONANCE SPECTROSCOPY (2H-MRS) STUDIES OF AQUEOUS HUMOR FORMATION IN THE RABBIT. James A. Wrllisf. Craig E. Crosson? and Y Thomas Schleichl. 1 Dept. of Chemistry and Biochemistry, University of California, Santa Cruz. California, USA and sTexas Tech University Health Sciences Center, Lubboch, Texas, USA. To evaluate the feasibility of using magnetic resonance spectroscopic techniques for the non-invasive measurement of aqueous humor dynamics, we previously demonstrated that aqueous formation in rabbits can be monitored by 2H-MRS (Willis, et al. lsS1). The natural abundance deuterfum signal arising from HDO in the anterior chamber is readily detected using a 7 mm, 2 turn surface coil placed in a co-planar orientation over the cornea. Following i.v. bolus administration of isotonic deuterium oxide (D20) the accumulation of HDO in the anterfor chamber, reflecting aqueous formation, can be readily monitored. Details of the technique and the results of ongoing experiments conducted at 4.7 T examining the feasibility of using this methodology to study pharmacologic regulation of aqueous humor formation in adult New Zealand White rabbits will be presented.
S.214