Download Consensual Ocular Hypertensive Response to Prostaglandin

Consensual ocular hypertensive response
to prostaglandin
Tzu Sung Chiang and Robert P. Thomas
The effects of intracameral injection of prostaglandin E, (PGEi) PGEi, and PGF:a in one eye
on the intraocular pressure (1OP) of both eyes and the systemic blood pressure were studied in
rabbits. PGE, and PGE:, 10 fig, consistently produced a contralateral 1OP rise and a lowering
of blood pressure, in addition to the well-known ipsilateral ocular effect. The consensual response to PGEi was not prevented by intracranial transection of the optic nerve, the oculomotor nerve, and the trigeminal nerve or by topical treatments with several PG antagonists
such as polyphloretin phosphate (PPP), 7-oxa-l3-prostynoic acid (7-OPA) and l-acetyl-2-(8chloro-10,ll-dihydrodibenz) (b, f) (1, 4) oxazepine-10-carbonyl) hydrazine (SC-19220). It was
prevented by pretreatment of the contralateral side with topical epinephrine and cross-infusion
of PPP into the lingual artery and enhanced by intravitreous PPP, topical PPP, topical 7-OPA,
topical 7-OPA vehicle, and transection of the trigeminal nerve. This potentiation is probably
due to a nonspecific irritation of the contralateral eye. Slow intravenous infusion of PGEt (0.79
fig per minute) produced a comparable IOP rise. It is suggested that the consensual ocular
hypertensive response to PG is due to the transfer of PG from the injected eye to the contralateral eye via the blood circulation.
Key words: consensual reaction, intraocular pressure, prostaglandin,
optic nerve, oculomotor nerve, trigeminal nerve, epinephrine,
polyphloretin phosphate, 7-oxa-13-prostynoic acid, SC-19220
C.
Intracranial stimulation of the trigeminal
nerve as well as stimulation of its nerve
endings at the iris did produce ipsilateral
ocular hypertension, presumably due to the
release of PG.2 5> G Another possible mechanism for consensual reaction would relate
the transfer of an active principle from the
ipsilateral eye to the contralateral eye by
way of the systemic blood circulation. Although the circulator)^ pathway was generally ruled out, the evidence against it
was mostly indirect.
The present report describes a consistent
and rapid rise in intraocular pressure (IOP)
of the contralateral eye following the intracameral injection of 10 /xg of PG in the
ipsilateral eye in rabbits. The role of several
cranial nerves and the effects of PG an-
'onsensual ocular hypertension has been
known to occur following subconjunctival
injection of nitrogen mustard,1 intracranial
stimulation of the trigeminal nerve,2 and intracameral injection of prostaglandin (PG) 3
or formaldehyde4 in rabbits. In general,
these consensual responses occurred inconsistently in terms of frequency and magnitude. The onset was usually slow.
The mechanism of the consensual response has been thought to result from an
antidromic reflex via the trigeminal nerve.1"3
From the Department of Ophthalmology, Medical
College of Georgia, Augusta, Ga. 30902.
Manuscript submitted Dec. 27, 1971; manuscript
accepted Jan. 17, 1972.
169
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Investigative Ophthalmology
March 1972
170 Chiang and Thomas
tagonists such as epinephrine, polyphloretin
phosphate (PPP), 7-oxa-13-prostynoic acid
(7-OPA), and l-acetyl-2-(8-chloro-10,lldihydrodibenz) (b, f) (1,4) oxazepine-10carbonyl) hydrazine (SC-19220)3- 7"9 on this
consensual response were also investigated.
Methods
Measurements of 1OP and mean arterial blood
pressure (BP). Albino rabbits weighing approximately two kilograms were anesthetized with 1
to 2 Cm. per kilogram of urethane administered
intravenously as a 25 per cent solution in distilled
water. The femoral artery was cannulated with No.
50 polyethylene tubing (PE 50) which was filled
with heparin solution and connected to a Statham
P 23 Db pressure transducer. The animal was
then placed in a prone position. The anterior chambers of both eyes were cannulated at the 12 o'clock
position with a 22 gauge needle connected by a
PE 50 tubing to a Statham P 23 Db pressure
transducer. A reservoir containing a balanced salt
solution10 and set at 30 mm. Hg height was also
connected to the transducer for calibration. The
changes in IOP and BP were recorded on a Sanborn Twin-Viso Recorder and a DR-8 Recorder
from the Electronics for Medicine, Inc., respectivelntracameral injection of PG. Immediately after
cannulation of both eyes, the needle was connected
to the transducer and the connection to the reservoir was turned off. The pressure in the transducer fell from 30 mm. Hg to the basal IOP level
within 10 to 15 minutes. As soon as the IOP was
constant, the anterior chamber of one eye was
further cannulated with a 25 gauge needle which
had been connected with a PE 20 tubing to a 50
fi\ Hamilton microsyringe and filled with PG solution. Approximately three minutes after the second
cannulation a constant volume (10 /*1) of PG
solution was injected into the anterior chamber.
IOP of both eyes and BP were continuously monitored for 30 minutes after injection.
Intravenous infusion of PGEt. PGEi (100 Mg per
milliliter) was infused via the ear vein or the
femoral vein for ten minutes at a rate of 3.9, 7.9,
or 19.7 fi\ per minute with the use of a Harvard
infusion pump (Model 940). IOP and BP were
monitored continuously during the infusion and
for ten minutes after infusion.
lntracranial transection of the optic nerve, the
oculomotor nerve, and the trigeminal nerve. Transection of the optic nerve was performed under
sodium pentobarbital anesthesia (30 mg. per kilogram, intravenously) and aseptic conditions. One
side of the skull was opened from the frontoparietal suture to approximately 1 cm. anterior to
the suture on the frontal bone. The dura was
separated from the frontal bone and the posterior
portion of the orbitosphenoid bone and cut open at
the optic foramen. The optic nerve was subsequently transected. The animal was tested for loss
of light reflex one hour and two weeks after the
operation.
Intracranial transection of the oculomotor and
the trigeminal nerves was performed acutely under
urethane anesthesia. The femoral artery and both
eyes were cannulated after the nerve transection.
Complete transection of the nerve was verified at
the end of experiment. To transect the oculomotor
nerve one side of the skull was opened approximately 1 cm. in diameter around the frontoparietal suture. The dura was opened and a portion of the cerebral hemisphere was removed. The
oculomotor nerve was approached along the posterior portion of the orbitosphenoid bone to presphenoid. The nerve was cut at the side of the
hypophyseal fossa before it enters the superior
orbital fissure.
The trigeminal nerve was transected as follows.
After one side of the skull was opened slightly
posterior to the frontoparietal suture, the dura
was cut open. A pair of tweezers was inserted along
the edge of the occipital lobs and then advanced
ventromedially along the posterior side of the
tendinous septum which separates the frontal
cranial cavity from the posterior cavity. Before the
tweezers were advanced to the fossa where the
trigeminal nerve enters the sphenoidal sulcus and
forms the semilunar ganglion, a small hill-like
structure could be felt. The nerve was transected
preganglionically by a quick scratch movement at
the orifice of the sphenoidal sulcus.
Drug treatments. One per cent Z-epinephrine
(0.1 ml.) was applied topically to the cornea and
distributed over the conjunctival sac 60 minutes
before the PG injection. Two per cent PPP solution was either applied topically (0.1 ml.) 60
minutes before the PG injection, injected into
the vitreous (10 fi\) 24 hours before the PG injection, or cross-infused into the right lingual artery
(0.04 ml. per minute) for 20 minutes followed by
PG injection two minutes later. 7-OPA, 0.1 per
cent, was either applied topically (0.05 ml.) for
5 minutes or infused intravenously at a dose of
1 mg. per milliliter per kilogram and 0.68 ml. per
minute before the PG injection. SC-19220 was
applied topically (0.1 ml. every 2 minutes for three
times) as a one per cent suspension followed by
PG injection 60 minutes later. SC-19220 was also
cross-infused into the right lingual artery for 20
minutes (1.2 mg. per milliliter; 0.04 ml. per
minute) followed by PG injection 2 minutes later.
Preparation of drugs. PG and 7-OPA were dissolved in 95 per cent ethanol (0.1 ml. for each
milligram of PG or 7-OPA) and diluted with 0.2
mg. per milliliter of sodium carbonate solution to
a final concentration of 1 mg. per milliliter. The
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Volume 11
Number 3
solution was stored in small test tubes (0.5 ml. per
tube) and kept in a freezer. Z-Epinephrine bitartrate solution was prepared freshly as a one per
cent free base in the balanced salt solution. PPP
(89.1 per cent pure) was dissolved in 0.1N NaOH
to a final concentration of 20 mg. per milliliter.
The solution was stored in a freezer. SC-19220 was
dissolved in 95 per cent ethanol and then diluted
with the balanced salt solution to a final concentration of 1.2 mg. per milliliter. The volume of
the 95 per cent ethanol used was 10 per cent of
the final volume. SC-19220 was also prepared as
a one per cent suspension in the balanced salt
solution with the use of a glass tissue homogenizer.
Results
IOP and BP responses to PGE,, PGE2,
and PGF2a. The responses of IOP and BP
to intracameral injection of PGE,, PGE2,
and PGF2« are shown in Fig. 1. At a dose
of 10 fig, PGE, and PGE2 produced a sustained ocular hypertension in the ipsilateral
eye, which reached the plateau response
within 10 to 20 minutes after injection. At
this dose both PGEt and PGE, also elevated IOP of the contralateral eye and
lowered BP. The maximal contralateral IOP
and BP responses occurred within 5 to 10
minutes after the injection. In comparison
with the response to 10 fig of PGE,, 1/xg of
PGE, also produced a similar rise in ipsilateral IOP in terms of magnitude and time
course but a small rise in contralateral IOP
and no decrease in BP. The ipsilateral IOP
rise following PGF2ft (10 fxg) was smaller
than that following PGE, or PGE,,. There
was no significant change in contralateral
IOP or BP following PGF,« injection. The
basal IOP and BP for groups tested with 1
Mg of PGE,, 10 Mg of PGE2, and 10 Mg of
PGF2« are shown in Table I, and those for
the 10 /ig of PGE, group are shown in
Table II.
Transection of cranial nerves. Table II
summarizes the effects of intracranial transection of the optic nerve, the oculomotor
nerve, and the trigeminal nerve on IOP
and BP responses to PGE,. Ipsilateral or
contralateral transection of the optic nerve
two weeks before did not affect the basal
IOP and BP or influence the response to
PGE,. The basal BP and IOP appeared
Consensual response to prostaglandin 171
Ipsilateral
+20-
a»
°- o
:ontralateral
o
§+10
LOP
xT^X
o
•E 0-
- ^
it
c
c
o
jr
O
-100 2 4 6 8 10 15 20 25 30
Time ( m i n)
Fig. 1. The responses of IOP and BP to intracameral injection of PG in rabbits. PGEi (1
Mg,
; 10 /ig,
), PCE2 (10
Mg,
), or PGFsa (10 fig,
) was
injected in a volume of 10 ii[ at 0 minutes. The
changes in IOP of both eyes and BP were continuously monitored for 30 minutes after the injection. The basal IOP and BP and the number of
experiments for each group are shown in Tables
I and II. Mean changes with one standard error at
some points are shown in the figure.
lower following transection of the oculomotor nerve, probably as a result of bleeding during partial decerebration. The absolute changes in IOP of both eyes following PGE, injection were also decreased.
Nevertheless, the change in contralateral
IOP expressed as the per cent of ipsilateral
IOP change after PGE, injection in this
group did not differ significantly from that
in the control group. Acute transection of
the trigeminal nerve always produced a rise
in IOP on the operated side, which subsided during the next 30 minutes when the
femoral artery and both eyes were cannulated. Bleeding due to the operation was
minimal. Intracameral injection of PGEt
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172 Chiang and Thomas
biocxligntivc Ophthalmology
March 1972
Table I. Basal IOP and BP
Treatments
Intracameral injection
PGE, 1 Aig/10 p\
PGES 10 jttg/10 pi
PGFS« 10 /tg/10 Ml
Intravenous infusion (PGE! 100 pg/m].)
3.9 /il/min.
7.9 juJ/min.
19.7 /u]/min.
"Mean ± standard error.
No.
of
experiments
5
5
3
8
12
5
in the operated eye produced IOP and BP
responses comparable to those in control
animals. However, when the contralateral
trigeminal nerve was transected, injection
of PGEt into the ipsilateral eye always produced a contralateral rise which was greater
than that in the control group, while the
ipsilateral IOP rise was the same.
Intravenous infusion of PGEj. Intravenous infusion of PGEt (100 /xg per milliliter) invariably produced an increase in
IOP and a decrease in BP (Fig. 2). At a
rate of 3.9 and 7.9 /.J per minute, the decrease in BP was around 5 mm. Hg, while
the increase in IOP continued during the
period of infusion. When PGEL was infused
at a rate of 19.7 /J. per minute, the decrease in BP was so severe that the rise in
IOP was lessened. Both IOP and BP returned to basal levels upon termination of
infusion. The basal levels of IOP and BP
for these experiments are also shown in
Table I.
Drug treatments. As shown in Table III,
the contralateral IOP response to PGEX injection was prevented by treatments with
topical epinephrine and by cross-infusion
of PPP into the lingual artery. Contralateral
ocular treatment with intravitreous PPP,
topical PPP, topical 7-OPA, and topical
7-OPA vehicle significantly enhanced the
consensual response to PGE.,. Intravenous
infusion of 7-OPA at the dose employed was
ineffective. There was a significant decrease
in basal IOP of eyes treated with topical
epinephrine or inb-avitreous PPP. When one
Basal IOP (mm. Hg)
Contralateral
PG-injected
eye
eye
20.3 ± 1.5°
20.8 ± 0.3
18.8 ± 0.9
19.6 ± 0.7
20.5 ± 0.7
16.7 ± 0.3
18.1 ± 0.7
18.1 ± 0.7
19.0 ± 0.6
Basal BP
(mm. Eg)
90.4 ± 6.5
101.5 ± 3.9
87.7 ± 2.9
81.0 ± 4.8
88.4 ± 3.3
83.5 ± 5.0
per cent SC-19220 was applied topically
three times on the contralateral eye, it
seemed to enhance the consensual response
to PGEi in one experiment (ipsilateral rise,
+43.0 mm. Hg; contralateral rise, +24.0 mm.
Hg). In another experiment, SC-19220 was
cross-infused into the contralateral lingual
artery (1.2 mg. per milliliter, 0.04 ml. per
minute for 20 minutes) and found ineffective in modifying the contralateral response
to PGEL.
Discussion
Intracameral injection of 10 /xg of PGE,,
PGE,, and PGF2« consistently elevated IOP
of the injected eye. Since injection of 1 /xg
of PGEi also elevated IOP of the injected
eye to the same degree, the ipsilateral IOP
response obtained following 10 [xg of PGE,
and PGE2 was probably at the maximal
level. PGFL« seemed to have weaker ocular
hypertensive action. This is consistent with
the data published by others.3
Consensual ocular hypertension has been
reported following injection of an eye with
various chemicals1' 3> 4 and following intracranial stimulation of the trigeminal nerve.Its occurrence was infrequent, its magnitude variable, and its onset slow. The consensual response to 10 /xg of PGE, or PGEas described in the present study was observed consistently in terms of frequency,
amplitude, and onset. It seemed to depend
on the dose and potency of PG injected.
Thus, 1 /.ig of PGE, produced consensual
response which was smaller than that pro-
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Consensual response to prostaglandin 173
Volume 1.1
Number 3
Table II. Effects of intracameral injection of PCE, (10 /ig per 10 ./.d) on the IOP
and BP following the intracranial transection of the optic nerve, the oculomotor
nerve, and the trigerainal nerve in rabbits
Treatments
Control
IOP (mm. Hg)
PGE,No.
BP (mm. Hg.)
Contralateral eye
injected eye
of
Maximum
Maximum
Maximum
experiments Basal increase Basal increase
%° Basal decrease
-8.4
+10.8
28.6 89.1
18.7
18.6
14
+38.1f
±1.5
± 1.5
± 3.4 ±2.7
±2.0
±0.5
±0.8
Contralateral optic nerve cut (2 wk.)
4
18.1
±1.5
+39.5
±2.5
20.1
±1.4
+14.5
±1.9
36.3 96.0
±3.2 ±5.8
-7.8
±1.8
Ipsilateral optic nerve cut (2 wk.)
5
19.1
±1.4
+40.9
±0.7
18.9
±1.0
+10.2
±3.1
24.8 94.4
±7.5 ±2.8
-6.4
±1.4
Contralateral oculomotor nerve cut
(acute)
5
15.3
±0.6
+26.0
±3.8
16.7
±0.8
+5.6
±0.9
23.5 71.0
±4.5 ±2.7
-4.0
±0.5
Contralateral trigeminal nerve cut
(acute)
4
18.8
±0.5
+36.9
±3.8
19.0
±1.6
+17.0
± 1.7
46.5 97.0
± 3.7 ±1.7
-6.5
±1.3
Ipsilasteral trigeminal nerve cut
(acute)
4
17.4
±0.5
+40.2
±2.8
19.2
±1.2
+9.9
±1.6
25.1 90.2
±4.9 ±3.1
-10.2
± 1.9
•Maximum increase in contralnternl eye/Maximum increase in PGEi-injoctecl eye x 100.
(Mean ± standard error.
Table III. Effects of various treatments on the response of intraocular pressure
and mean femoral arterial blood pressure to intracameral injection of PGE, (10
/xg per 10 /A) in rabbits
Treatments
Control
Topical epinephrine (1 mg. in 0.1
ml., 60 min.)|
IOP (mm, Hg)
PGE,Contralateral eye
injected eye
BP (mm. Hg)
No. of
experiMaximum
Maximum
Maximum
ments Basal increase Basal increase
% • Basal decrease
28.6 89.1
14
+38.1
+10.8
-8.4
18.6t
18.7
±3.4 ±2.7
±0.5
±2.0
±1.5
±1.5
±0.8
19.2
14.5
4
+37.5
+2.6
7.9 88.2
-8.0
±0.8
±4.2
±0.6
±1.0
±3.3 ±6.5
±3.6
Intralingual artery infusion PPP
(0.8 mg./0.04 ml./min., 20 min.)J
4
15.4
±1.3
+40.2
±3.4
13.5
±1.4
+2.8
±0.8
6.6
±1.8
92.3
±2.2
-7.7
±1.8
Intravitreous injection PPP (200 (ig
in .10 fi\, 2 4 h r . ) |
5
20.2
±0.6
+47.7
±2.0
13.2
±1.2
+22.7
±3.7
47.8
±8.4
90.0
±3.6
-2.0
± .1.6
Topical PPP (2 mg. in 0.1 ml., 60
min.) J
3
19.7
± 0.7
+43.3
±4.1
19.5
±2.2
+22.2
± 3.5
-7.3
± 0.9
Intravenous infusion 7-OPA (1 mg./
ml./Kg., 0.68 ml./min.)|
5
17.0
±1.9
+36.8
±3.0
16.1
±2.0
+13.9
±1.6
50.6 89.0
±3.2 ± 1.5
38.2 89.2
±3.7 ±4.7
-5.2
±2.3
Topical 7-OPA (50 ng in 50 /*],
5 min.)|
9
19.1
±0.9
+36.0
±2.0
20.2
±1.4
+18.1
±1.4
50.2
±2.7
96.5
±4.2
-11.4
± 2.3
Topical 7-OPA vehicle (50 fil,
5 min.) J
5
20.1
±0.5
+43.3
±2.6
20.4
± 1.3
+19.7
±1.8
45.9 97.7
±3.7 ±2.8
-9.9
±1.9
"Maximum increase in contralateral eve/Max i mu in increase in PGE-injected eye x .100.
fMean + standard error.
t Treatments on the contralateral side only.
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Investigative Ophthalmology
March 1972
174 Chiang and Thomas
1
1
T
1
1
1
1
1
1
1
1
0 1 2 3 4 5 6 7 8 9 10
T i m e (m i n )
15
20
Fig. 2. The response of IOP and BP to intravenous infusion of PGEi in rabbits. PGEi (100 fig
per milliliter) was infused via the ear vein or the
femoral vein at a rate of 3.9 fi\ per minute
(
), 7.9 fi\ per minute (
), or
19.7 fi\ per minute (
) beginning at 0
minute. The changes in IOP of both eyes and BP
were continuously monitored during the infusion
and for 10 minutes after infusion. The basal IOP
and BP and the number of experiments for each
group are shown in Table I. Mean changes with
one standard error at some points are shown in
the figure.
duced by 10 Aig of PGEX, and 10 Mg of
PGFoa did not produce a rise in IOP in the
contralateral eye.
The consensual response has been generally thought of as an antidromic reflex
via the trigeminal nerve. Davson and Machett1 did not obtain a rise in IOP following
subcutaneous injection of nitrogen mustard
but did encounter a consensual rise in IOP
following subconjunctival injection. They
suggested a neuroreflex mechanism for the
consensual IOP rise. In discussion of the
mechanism of consensual ocular response
(IOP rise, increase in protein in aqueous
humor, and increase in temperature of
ciliary body), Perkins2 cited four evidences
in favor of the nervous pathway: (1) The
type of response is the same in both eyes.
(2) The onset of response is about the same
in both eyes. (3) The association between
depth of anesthesia and the frequency of
the contralateral changes suggests a ner-
vous pathway. (4) Stimulation of an intact
trigeminal nerve on one side did not produce consensual reaction after cutting the
nerve on the contralateral side in seven
experiments. However, the first three evidences are not in conflict with other hypotheses (discussed below). Furthermore,
no experimental data were available in the
text for the last evidence. In his experiments with 11 rabbits which had the fifth
nerve cut two to four weeks before, stimulation of the nerve distal to the section
produced more cases of consensual reaction
than did stimulation of the nerve on the
cranial side of the section. This would
argue against the nervous pathway for the
consensual reaction.
The data from trans ection of cranial
nerves in the present experiments have
demonstrated that neither the optic nerve,
the oculomotor nerve, nor the trigeminal
nerve is involved in the consensual response following intracameral injection of
PGEj. In fact, mechanical irritation of the
contralateral trigeminal nerve caused by
transection of the nerve seemed to enhance
the consensual response to ipsilateral PGE,
injection.
A wide variety of ocular insults generally
results in a similar ocular reaction, namely,
a rise in IOP, miosis, and hyperemia in the
treated eye. Irritation of the trigeminal
nerve endings in the treated eye has been
suggested as the common cause.11 Indeed,
irritation of the trigeminal nerve consistently produces these ocular reactions on the
same side.2 The great variation in the consensual response following various ocular
irritation does not seem to suggest the involvement of contralateral trigeminal nerve
in this response.
Two other explanations are possible for
the consensual response following PG injection. There might be some connection,
vascular or extracellular fluid, between both
eyes. In rabbits, each optic nerve foramen
communicates with the cranial cavity and
also with its fellow across the midline. The
communication between the left and right
orbits is approximately 5 mm. in diameter.
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Volume 11
Number 3
Consensual response to prostaglandin 175
PG injected into one eye could pass to the
opposite eye through this access between
them. The most likely pathway seems to
be the systemic blood circulation. The decrease in blood pressure after intracameral
injection of PGE, strongly suggests that the
PG reaches the systemic blood circulation.
Although it is generally acknowledged that
PGEX, PGE,, and PGF,« are rapidly inactivated by the pulmonary circulation12
and that a single intravenous injection of
PGE, elevates IOP only transiently,13 a
continuous supply of PG from the injected
eye via the blood circulatory system to the
contralateral eye might possibly produce
the observed contralateral IOP rise in the
present study. Therefore, a slow continuous
intravenous infusion of PGEL was undertaken. When the rate of infusion was approximately 0.8 fxg per minute, the rise in
IOP continued during the infusion, reaching the similar magnitude as that observed
in consensual IOP rise. At a higher rate of
infusion (approximately 2 jig per minute)
the IOP rise was diminished due to a decrease in blood pressure (Fig. 2).
The question remained to be answered is
whether the injected PG is wholly responsible for the contralateral IOP rise in the
present experiments. PGE.. and PGF,« are
present in rabbit irises.1A>xr> Irritation of
ipsilateral eye by injected PG could release
PG from the iris. Release of other active
substance from the injected eye is also possible. However, there is no evidence for
the latter conjecture.
Topical epinephrine and cross-infusion
of PPP into the lingual artery have been
shown to antagonize the ipsilateral ocular
response to PG or other irritants.3'4> 1G The
consensual response to PGEX was also significantly prevented by these pretreatments.
This suggests the involvement of PG in the
contralateral IOP rise. Topical treatments
with PPP, 7-OPA, and SC-19220, which are
known PG antagonists in vitro,s> 9 have resulted in potentiation of the consensual response. Intravitreous injection of PPP which
has been shown to be very effective in preventing the IOP rise following intravenous
injection of PG17 also resulted in potentiation. Since topical application of 7-OPA
vehicle also enhanced the consensual response, the potentiation was probably due
to a nonspecific irritation of the eye. It is
interesting to recall that irritation of the
contralateral trigeminal nerve due to transection of the nerve also induced potentiation.
We would like to thank Dr. John E. Pike of The
Upjohn Co. for the generous supply of prostaglandin, Dr. Josef Fried of the University of
Chicago for 7-OPA, Dr. John H. Sanner of C. D.
Searle & Co. for SC-19220, and Dr. B. Hogberg of
Leo Lab. for PPP.
REFERENCES
1. Davson, H., and Machett, P. A.: The control of the intraocular pressure in the rabbit,
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