(Investigative Ophthalmology and Visual Science. 2001;42:1328-1337.)
© 2001
by The Association for Research in Vision and Ophthalmology, Inc.
Facilitation of Artificial Retinal Detachment for Macular Translocation Surgery Tested in Rabbit
Frank Faude1,
Susanne Wendt2,
Bernd Biedermann2,
Ulrich Gärtner2,
Johannes Kacza3,
Johannes Seeger3,
Andreas Reichenbach2 and
Peter Wiedemann1
1 From the Department of Ophthalmology, Eye Hospital; the
2 Paul-Flechsig Institute for Brain Research; and the
3 Institute of Veterinary Anatomy, Leipzig University, Germany.
 |
Abstract
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PURPOSE. For macular translocation surgery, the native attached retina has to be
detached either locally or completely. Although different surgical
techniques are used, there is a general search for supporting
procedures that facilitate and accelerate the retinal detachment.
METHODS. Pars plana vitrectomies were performed in pigmented rabbits. In all
experimental groups, a local retinal detachment was created by infusing
the test solution with a thin glass micropipette attached to a glass
syringe. In control animals a standard balanced salt solution was used
at room temperature, in combination with a standard vitrectomy light
source. In two test groups, a calcium- and magnesium-free solution was
used for the vitrectomy, under illumination by a standard light source
in group I (solution at room temperature) and group II (solution heated
up to body temperature). In group III the rabbits were dark-adapted for
half an hour, and then, during surgery, a red filter was used in front
of the light source (standard balanced salt solution at room
temperature). After the rabbits were killed at the end of surgery, the
adherence of the retinal pigment epithelium (RPE) to the neural retina
in the detachment area was quantified microscopically, and the
morphologic integrity of the detached retinal tissue was examined by
light and electron microscopy. No electrophysiology was performed.
RESULTS. In all four groups, it was possible to detach the retina. The maximum
adherence of the RPE cells to the neural retina was observed in the
control group. Virtually no decrease in adherence was found in test
group II (36°C solution without calcium and magnesium), whereas a
significant decrease was seen in both group I (calcium- and
magnesium-free solution at room temperature) and group III (dark
adaptation–red light technique; standard balanced salt solution at
room temperature). In none of the experimental groups was any obvious
damage of the retinal structure observed, even after exposure to the
test solutions for 60 minutes.
CONCLUSIONS. Both dark adaptation (red illumination) and the use of a calcium
chloride– and magnesium chloride–free solution (at room temperature)
can facilitate retinal detachment in macular translocation surgery.
Both techniques are proposed as a gentle support for the operation,
because they protect an intact RPE cell layer and do not cause retinal
damage at the ultrastructural level.
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Introduction
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Age-related macular degeneration (AMD) is the most frequent
cause of blindness in people aged 50 years and more.1
The
development of subfoveolar neovascularization is one of the dominant
reasons for the loss of vision in AMD. Because of the poor prognosis
regarding visual function after laser treatment,2
3
4
new
operative techniques have been developed to treat this
vision-threatening disease. The surgical excision of subfoveal
membranes, which represent approximately 75% of all choroidal
neovascularizations in AMD, does not result in a convincing improvement
of visual function.5
6
As another approach, the
translocation of the macula onto a healthy tissue was
considered.7
8
Machemer and Steinhorst9
10
were the first to perform the technical procedure of rotating the
retina and translocating the fovea. Macular translocation may
constitute a suitable therapy for AMD. Promising results have been
reported,11
and a critical review has recently been
published.12
The main problem with the procedure lies in
the artificial separation of the neural retina from the retinal pigment
epithelium (RPE)—a procedure that is necessary to translocate the
macula but is very difficult and time consuming.
The mechanisms of retinal adhesion are complex and multifactorial,
because a variety of physical and physiological forces impinge on the
subretinal space and its matrix.13
However, it has been
demonstrated that retinal adhesion may be modulated by a variety of
conditions, including changes in local osmolarity, pH, and other ionic
concentrations.13
In particular, a reduction of calcium
and magnesium in the subretinal space decreases retinal adhesion, even
in vivo14
15
—an effect that is reversible within a few
minutes.16
Temperature has also been shown to affect the
adhesive retinal force. In enucleated eyes it is possible to reduce
retinal adhesion by raising the eyes to body temperature. This effect
is increased by incubating the tissue in a calcium- and magnesium-free
solution at 37°C.17
Furthermore, the effect of light
exposure on retinal adhesion has been investigated in rabbits. A
significant difference in the retinal adhesive forces was found between
light- and dark-adapted nondetached retinas.18
Thus, there are several promising approaches to reducing retinal
adhesion in macular translocation surgery. However, only a few of the
mentioned procedures have been applied in vivo14
15
; most
have been tested in vitro,16
17
18
19
although retinal adhesion
is known to change rapidly after enucleation.13
Furthermore, the cleavage zone between photoreceptors and RPE was
examined,14
18
19
but none of the studies was devoted to
examining any possible damaging side effects on the (inner) retinal
tissue. Such side effects, however, would greatly limit or even prevent
the application of a technique to human retinal surgery. Thus, we
decided to perform a series of experiments in an in vivo model, the
rabbit, to assess both retinal adhesion and structural maintenance of
the retina by using a calcium- and magnesium-free solution at low and
high temperatures (with standard illumination) and a standard balanced
salt solution after dark adaptation and surgery under dim red light.
The degree of the RPE’s adherence to the neural retina was taken as an
index for the force of adhesion.17
As a main point, the
structural integrity of the detached retinas was studied by light and
electron microscopy throughout the thickness of the tissue up to the
inner limiting membrane.
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Materials and Methods
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Retinal Surgery
All experiments were performed in accordance with the ARVO
Statement for the Use of Animals in Ophthalmic and Vision Research.
Pigmented 2- to 4-kg rabbits (New Zealand) of both sexes were used.
Animals were kept for 12 hours at daylight. A mixture of ketamine
hydrochloride (1 ml/kg) and xylazine hydrochloride (1 ml) was used to
anesthetize the animals. The pupil of the right eye was dilated by a
topical application of 1% tropicamide and 5% phenylephrine
hydrochloride. The eye was subsequently protruded and immobilized. Pars
plana sclerotomies were performed under an operating microscope with a
20-gauge needle in the upper nasal and upper temporal quadrants 3 mm
behind the limbus. A 4-mm infusion cannula was inserted through one
sclerotomy. A circumscript vitrectomy was performed in the area of the
planned retinal detachment through the other sclerotomy site, by using
a vitrectomy system (Ocutome; Alcon Surgical, Irvine, TX). Thin glass
micropipettes (40-µm inner diameter), attached to a 250-µl glass
syringe (Hamilton, Reno, NV) and introduced through the sclerotomy,
were used to raise a subretinal bleb and to create a retinal
detachment. When the tip of the pipette was positioned close to the
inner limiting membrane, a stream of the solution was administered to
the retinal surface that produced a small retinal hole and a subretinal
bleb. The rate of subretinal fluid injection was approximately 300
µl/min. The sclerotomies and the overlying conjunctiva were then
closed with 6-0 Dexon (Dexon GmbH, Spangenberg, Germany)
sutures.
In this study, we used balanced salt solutions BSS plus I and II (Alcon
Pharma, Fort Worth, TX) as a standard intraocular solution and BSS plus
I as a calcium chloride– and magnesium chloride–free intraocular
solution for infusion (vitrectomy) and bleb formation (Table 1)
. The latter solution was chosen to guarantee applicability in
human patients, standardization, and comparability with the results of
others.20
In earlier animal experiments,
Ca2+-containing and
Ca2+-free Hanks’ solutions were
used.14
There are no notable differences between Alcon BSS
plus and Hanks’ solution in ionic composition, osmolarity, and pH.
Random charges of BSS plus I and II and BSS plus I (Alcon) were
measured for their pH and osmolarity (Osmomat 030; Gonotec, Berlin,
Germany); no significant differences were found between the two
solutions (pH 7.27 versus 7.25; 313.8 mOsm versus 298.5 mOsm,
respectively; the latter difference of 15 mOsm, due to the omission of
CaCl2, MgCl2, and glucose,
is not sufficient to account for the observed changes in
adhesion13
).
The calcium- and magnesium-free solutions were used either at
room temperature (21°C –23°C) or at 36°C, respectively. In the
latter case, the bottles and tubes were insulated to maintain the
temperature of the solution until it entered the eye. In one series of
experiments, the animals were dark adapted, and the surgery was
performed under a dim red light. For this purpose, a filter (diameter,
60.0 mm; thickness, 3.0 mm; 
c = 665 ± 6
nm; model RG 665; Schott Glas, Mainz, Germany) was placed in front of
the light source. Despite reduced visibility of the retina under these
conditions, the surgery was feasible.
For assessment of retinal adhesion, both vitrectomy and retinal
detachment were performed within approximately 5 to 10 minutes. To
study the structural maintenance of the retinas, the tissue was
examined after 60 minutes’ exposure to the test solution (continuous
perfusion of the eyes in situ), because longer times are required for
artificial retinal detachment in humans than in rabbits. We created the
retinal detachment in regions B and C as defined by Endo et
al.17
The area of detachment was labeled by producing four
endodiathermic points at its margins. After the end of the experiments,
the animals were killed and the eyes enucleated. Table 2
summarizes the experimental conditions for the controls and the three
experimental groups.
Preparation of Retinal Tissue
Immediately after enucleation, the sclera was circumferentially
dissected 2 mm posterior to the limbus. Four radial-relaxing incisions
toward the optic nerve were made in the sclera, and the sclera was
peeled away from the periphery to the optic nerve. Subsequently, the
choroid and the RPE were peeled off. The detached retinal area (the
bleb within the borders of the four endodiathermic points) was excised.
Its size (approximately 3.5 mm in diameter) was almost equal throughout
the series of experiments. It was then placed on slides (with its
photoreceptor surface up) and either used for quantification of the
adherent RPE or immersion-fixed for electron microscopy.
Quantification of the Adherent RPE
The unstained detached retinal tissue was studied by a
conventional light microscope (Jenaval; Carl Zeiss, Oberkochen,
Germany). With a camera CF 8/4 (KAPPA optoelectronics GmbH, Gleichen,
Germany) in combination with a software program (AnalySIS; SIS
Software Imaging; Münster, Germany) images were obtained at the
level of the photoreceptor outer segments. When a x3.5 lens was used,
almost the total bleb area was visualized at once. A computer and the
image analysis software (AnalySIS; SIS) were used to calculate the
amount of adherent RPE on the detached retina in relation to the area
of the detached retina. A measuring raster was displayed on the image
of the retinal surface. Within the individual squares of a raster (each
corresponding to 300 x 300 µm at the retinal surface) along
both diagonals (i.e., 12 squares for each bleb), the natively black RPE
areas were binarized. Thereafter, the percentage of the RPE
cell-containing (black) area was calculated in comparison with the
total retinal surface area. This percentage was used as an indirect
measure of retinal adhesion.
This assay was introduced by Endo et al.17
in an in vitro
study. It should be noted that in comparison with their data (80% and
more of the total retinal area with adherent RPE),17
we
found much lower levels (generally <10% as a mean; cf. Fig. 2
). This
discrepancy is probably due to methodical differences: Whereas Endo et
al. peeled the retina from the underlying tissue using jeweler’s
forceps (i.e., exerted a force that may have caused a disruption
anywhere between the retina and the fixed sclera, in principle), we
injected a solution between the retina and the RPE. Under the latter
condition, by definition, only local RPE adherences to the retina were
possible. Furthermore, Endo et al. reported that their peeling rate was
approximately 120 mm/min, whereas in our case the detachment rate was
lower by at least one order of magnitude (the 3–4-mm diameter bleb was
created within approximately 20 seconds).
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Figure 2. Quantitative assessment of retina–RPE adhesion. Test groups are as
described in Figure 1
. *Significant differences compared with group I
(**P < 0.1, ***P < 0.01).
|
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Because the collection of the assayed areas was independent of any bias
of the examiner, this part of the experiments was not performed as a
blind study (i.e., the examiner was aware of the treatment group
studied). The data (percentages of the RPE cell-containing area, from
each 12 assayed squares of 40 animals studied) were analyzed by
computer (SPSS software; SPSS Science, Chicago, IL) for possible
correlations with the four experimental groups or with the sex of the
animals. Although there was no dependence on the sex of the animals
(data not shown), the Mann–Whitney test results revealed significant
differences between the experimental groups (see Fig. 2
).
Electron Microscopy
The detached retina was fixed in a buffered mixture of 2.5%
glutaraldehyde and 3% paraformaldehyde (PFA) for 3 hours and
afterward in 4% PFA overnight, rinsed, and post-fixed in 1% osmium
tetroxide for 2 hours. The tissue was then rinsed, dehydrated in
ethanol, and stained overnight in 70% ethanol saturated with
uranylacetate. After further dehydration in absolute ethanol and
propylene oxide, the samples were embedded in Araldite (Ciba–Geigy,
Basel, Switzerland) or Durcupan (Fluka, Neu-Ulm, Germany) and sectioned
on an ultramicrotome (Ultracut; Leica, Heidelberg, Germany). Most of
the ultrathin sections were stained with lead citrate. They were
studied using an omega electron microscope (Leo EM 900 or EM 912;
Zeiss). Some semithin sections were cut, stained with cresyl violet,
and studied by light microscope.
Another series of fixed retinas, as described, were used for scanning
electron microscopy. After fixation (1 hour in 1% osmium tetroxide
buffered in 1% phosphate buffer [PB] at 4°C), the tissue was
rinsed three times for each 10 minutes in 1% PB and dehydrated in
ethanol (up to the final three times in 100%). Thereafter,
critical-point drying (CPD 030; Bal-Tec, Balzers, Lichtenstein) was
performed. The tissue was then placed on stubs by means of
self-adhering carbon tabs and sputtered with Au (thickness, 20 nm) by
using argon plasma (MED 020; Bal-Tec) for 40 seconds at 40 mA, with a
probe–target distance of approximately 50 mm. The tissue was studied
by microscope (Leo 1430; Zeiss).
All morphologic work was organized as a blind study (i.e., the examiner
was masked to the treatment group).
|
Results
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Retina–RPE Adhesion
Under all experimental conditions tested, subretinal blebs
and retinal detachment were created easily within a few minutes. There
were, however, apparent differences in the amount of adherent RPE.
Figure 1
shows samples of neural retinas (with photoreceptor outer segments up)
after retinal detachment had been induced under different conditions.
The lower magnifications (Fig. 1
, left column) provide a view of larger
retinal areas (1.7 x 2.2 mm), whereas the higher magnifications
(Fig. 1
, right column) show arrangements of individual adherent RPE
cells. It is apparent that at room temperature, less RPE was adherent
when the retinal detachments were performed with the calcium- and
magnesium-free solution (Figs. 1C
1D)
than when performed with a
standard intraocular solution (Figs. 1A
1B)
. By contrast, if the
calcium- and magnesium-free solution was used at body temperature, the
adherence of RPE to the neural retina was similar to that under
standard conditions (Figs. 1E
1F)
. When the retinal detachment was
created with the standard solution in dark adapted animals, virtually
no RPE was adherent to the neural retina (Figs. 1G
1H)
. Similar
results were obtained when scanning electron micrographs were studied
(compare with Figs. 4A
4B
4C
). In some cases, large sheets of
continuous RPE adhered to the light-adapted retina after detachment in
standard solution (Fig. 4A)
. This was never observed when the calcium-
and magnesium-free solution was used or when the animals had been dark
adapted.
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Figure 1. Qualitative assessment of retina–RPE adhesion. Artificially detached
unstained retinas (photoreceptor surface up) shown at lower
(left column: retinal areas, 1.7 x 2.2 mm) and
higher magnification (right column: retinal area, each
0.5 x 0.6 mm). The following experimental conditions were used:
(A, B) control group: standard intraocular
solution containing calcium and magnesium, room temperature, light
adaptation; (C, D) test group I: intraocular
solution without calcium and magnesium, room temperature, light
adaptation; (E, F) test group II:
intraocular solution without calcium and magnesium, 36°C, light
adaptation; (G, H) test group III: standard
intraocular solution, room temperature, dark adaptation. Adherent RPE
cells appear as black dots.
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Figure 4. Scanning electron microscopy of the sclerad surface of retinas detached
in standard intraocular solution containing calcium and magnesium, at
room temperature with light adaptation (A); calcium- and
magnesium-free solution, room temperature, light adaptation
(B); and standard intraocular solution, room temperature,
dark adaptation (C). Whereas large plates of adherent RPE
(A, right) were regularly found under standard
conditions, such plates were never observed when the calcium- and
magnesium-free solution was used or when the animals were dark adapted.
Scale bar, 30 µm.
|
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Figure 2
shows the statistical analysis of these observations as a box plot
diagram. A highly significant reduction in RPE adherence was achieved
by using the calcium- and magnesium-free solution at room temperature
(P < 0.01) and, particularly, by dark adaptation of
the surgically treated eyes (P < 0.001).
Morphologic Integrity of the Detached Retina
Because the use of a calcium- and magnesium-free solution may
exert damaging effects on the neural retina, the structural maintenance
of the tissue was studied after retinal detachment in this and in the
control solution. To our surprise, there was considerable intraretinal
swelling immediately after the detaching procedure (5–10 minutes),
even if the standard solution was used. The degree of swelling was
usually stronger under control conditions (Fig. 3B
) than with the calcium- and magnesium-free solution (Fig. 3A)
. A
transmission electron microscopic analysis of the outer segments of the
photoreceptor cells revealed no apparent difference between the two
conditions (Figs. 3C
3D)
. Scanning electron microscopy
(Figs. 4A
4B
4C
) also failed to demonstrate visible effects of the
experimental conditions on the maintenance of photoreceptor segments.
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Figure 3. Morphologic maintenance of the detached retinas immediately
after detachment surgery (after 5–10 minutes). (A,
B) semithin sections; (C, D)
transmission electron micrographs. (A, C)
Standard intraocular solution without calcium and magnesium;
(B, D) control conditions (standard intraocular
solution containing calcium and magnesium). Although intraretinal
swelling was visible, even at the light microscopic level
(A, B; arrows), the outer segments of
the photoreceptor cells were rather well maintained at the electron
microscopic level (C, D).
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Because macular translocation surgery is often time consuming,
the retinas were further investigated by electron microscope after a
1-hour exposure to the test solution (Figs. 5
6
7)
. After this time, ultrastructural alterations of the tissue were
observed under all conditions studied, although the most severe lesions
were found in the retinas detached under standard conditions (Fig. 5) .
The lesions included extracellular and perinuclear edema (empty spaces,
indicated by asterisks in Figs. 5
6
7
), swelling of mitochondria
(Figs. 5
6
7
; arrows), and distortion of photoreceptor outer segments
(Figs. 5E
6E
; double arrows), the latter of which was rarely observed
in the dark-adapted retinas (Fig. 7E)
. It can be safely concluded that
neither dark adaptation nor the use of a calcium- and magnesium-free
solution caused retinal damage exceeding that observed under standard
conditions; rather, these two conditions improved the maintenance of
the retinal ultrastructure.
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Figure 5. Ultrastructure of the detached retina after a 1-hour exposure to a
standard intraocular solution containing calcium and magnesium, at room
temperature with light adaptation: (A) vitread retinal
surface and nerve fiber layer; (B) inner plexiform layer;
(C) outer nuclear layer; (D) photoreceptor inner
segments; (E) photoreceptor outer segments.
There was considerable extracellular and perinuclear edema
throughout the retina proper (A, B, and
C;  ). Within the subretinal space, most of the
mitochondria in the inner segments of photoreceptors were swollen
(D, arrows), and many outer segments were
severely distorted (E, double arrows). Scale
bars, 2 µm.
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Figure 6. Ultrastructure of the detached retina after a 1-hour exposure to an
intraocular solution without calcium and magnesium, at room temperature
with light adaptation: (A) vitread retinal surface and nerve
fiber layer; (B) inner plexiform layer; (C) outer
nuclear layer; (D) photoreceptor inner segments;
(E) photoreceptor outer segments. Extracellular and
perinuclear edema was found in the retina (A and
C; ), but most of the photoreceptor inner segments
contained apparently intact mitochondria (D), and the
distortion of the outer segments was less pronounced (E)
than with standard solution. The arrows in (B)
and (D) point to mitochondria in various stages of swelling.
The double arrows in (E) show distorted disks
within photoreceptor outer segments. Scale bars, 2 µm.
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Figure 7. Ultrastructure of the detached retina after a 1-hour exposure to a
standard intraocular solution at room temperature. The dark-adapted
animal underwent surgery under dim red light: (A) vitread
retinal surface and nerve fiber layer; (B) inner plexiform
layer; (C) outer nuclear layer; (D) photoreceptor
inner segments; (E) photoreceptor outer segments. There was
not much extracellular edema (C, ), but several
mitochondria were swollen in both the inner plexiform layer
(B) and the photoreceptor inner segments
(D). The outer segments of most photoreceptors were rather
well maintained (E). The arrows in (B)
and (D) point to mitochondria in various stages of swelling.
Scale bars, 2 µm.
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Discussion
|
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If the macula is to be translocated onto an area of healthy
RPE, as described by Machemer and Steinhorst9
10
in
patients with AMD, strong mechanical forces are necessary to separate
the neural retina from the RPE. Diminishing the adhesive forces between
retina and RPE is highly desirable to reduce the duration of surgery
(i.e., the accumulation of intraoperative risks) as well as to minimize
the damage of both tissues caused by mechanical stress (i.e., the
postoperative risks due to holes in the RPE sheath and/or to
photoreceptor cell damage, for instance). It should be kept in mind,
however, that a procedure suitable to solving these problems may cause
intraretinal damage, which then may worsen the long-term prognosis of
the surgery. The present study was designed to provide data that allow
for clear-cut conclusions regarding the question of which of the
methods tested is preferable for use in human retinal surgery. Although
there are interspecies differences in retinal
adhesion,13
21
the principal mechanisms have been shown to
be similar in rabbits and primates,13
21
and the rabbit
thus seems to be an applicable model for this purpose. In this study,
no electrophysiology was performed; rather, our conclusions are based
on ultrastructural examination of the tissue.
Calcium- and Magnesium-Free Solutions: Reduced Retinal Adhesion and
No Additional Damage to the Tissue
Our data show that a calcium- and magnesium-free solution,
if used at room temperature, reduces retinal adhesion. This is in
accordance with earlier data obtained from human eyes after
death19
21
and from living rabbit eyes,14
21
in which it has been shown that only approximately 30% of normal
retinal adhesive force remains in a low-calcium
environment.14
Thus, there is ample evidence for the
conclusion that the absence of calcium in the subretinal space helps to
prevent RPE adhesion to the overlying retina. The reason for calcium’s
effect(s) on retinal adhesion is still unclear. The calcium
concentration may affect the interphotoreceptor matrix, subretinal
transport processes, and subcellular components of the
RPE.13
14
22
The use of a calcium- and magnesium-free solution, in addition to
decreasing the duration of surgery23
and preventing the
codetachment of RPE sheets together with the retina, also preserves the
outer segments of the photoreceptors (Fig. 6E
versus Fig. 5E
).
Moreover, it caused no specific structural damage of the retina proper
(Figs. 3A versus Fig. 3B
), even when the solution was applied over a
time of 1 hour (Fig. 5
versus Fig. 6
). Machemer and
Steinhorst9
observed a loss of some outer segments of
photoreceptors when they used a standard balanced salt solution. We
also found some degree of damage to the outer segments of the
photoreceptors as well as to various intraretinal structures (Figs. 3B
3D
5) when the balanced salt solution was used. In comparison to these
alterations, the damaging effects of the calcium- and magnesium-free
solution (Figs. 3A
3C
6)
were less rather than more pronounced.
Similar observations have been published, in preliminary form, by other
investigators.24
25
Body Temperature: Reversed Effect of Calcium- and
Magnesium-Free Solutions
Warming to body temperature of the calcium chloride- and magnesium
chloride-free solution seemed to be a method for further weakening
retinal adhesive forces, in that an adhesion-reducing effect of
elevated temperatures had been reported.17
In our
experiments, we obtained contradictory results (Figs. 1E
1F
2)
. The
reasons for this discrepancy are unclear, although significantly
different experimental conditions were used. The study of Endo et
al.17
was performed on enucleated eyes. In our in vivo
experiments, the warming up of the calcium- and magnesium-free solution
produced results that were not superior to those obtained with the
standard balanced salt solution.
Dark Adaptation: Retinal Detachment Facilitated and
Reduced Retinal Damage
We found a markedly reduced loss of RPE cells when surgery
was performed in dark-adapted animals under a dim red light (656 nm).
This is in accordance with the data of Owczarek et
al.18
who found that a 20% stronger force was necessary
to detach a retina in light-adapted eyes than in dark-adapted ones.
They noted that in dark-adapted eyes the cleavage occurred primarily in
the outer segments, whereas in light-adapted eyes the RPE was more
extensively involved.18
The normal function of
photoreceptor cells depends on multiple interactions between the
photoreceptors and the RPE cells. These interactions are partly
mediated by the interphotoreceptor matrix (IPM) surrounding the
photoreceptor segments and the RPE microvilli. In the rat retina, the
IPM has been shown to undergo a major shift between light and dark
adaptation.26
In light adapted rats, there was a strong
concentration of densely stained IPM in the apical outer segment zone,
at the interface to the RPE. This may be one reason for the strong
adherence of RPE to the neural retina under standard illumination
conditions. The underlying mechanism of the light-evoked IPM changes
could be a light-induced release of calcium by the photoreceptors into
the interphotoreceptor space.27
28
This may also be one of
the reasons that RPE cell loss is decreased in the calcium- and
magnesium-free solution. During dark adaptation, the
distribution of the IPM is changed. The interstitial zone of the IPM is
more concentrated, and the basal outer segment concentration is
lost.26
This could be the explanation for the decrease of
RPE cell loss in dark-adapted animals.
Although further research is necessary to reveal the exact mechanism(s)
of the effects of dark adaptation onto retinal adhesion, it can be
stated that among the procedures tested in our study, dark adaptation
is a very effective means to reduce retinal adhesion (Fig. 2)
and
causes reduced damage to the retina, particularly to the photoreceptor
outer segments (Fig. 7)
. Thus, both the dark
adaptation technique and the use of calcium- and magnesium-free
solutions are proposed as useful tools for creating the artificial
retinal detachment in macular translocation surgery.
|
Footnotes
|
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Supported by the Retina Research Foundation, Houston, Texas; the
Bundesministerium für Bildung, Forschung, und Technologie (BMBF);
the Interdisciplinary Center for Clinical Research at the
University of Leipzig (01KS9504, Project C1 and C5); and the
Deutsche Forschungsgemeinschaft, Graduiertenkolleg
"Intercell" (GRK 250/2-99).
Submitted for publication June 1, 2000; revised October 2 and December
7, 2000; accepted January 12, 2001.
Commercial relationships policy: N.
Corresponding author: Peter Wiedemann, Eye Hospital, Leipzig
University, Liebigstrasse 10-14, D-1403 Leipzig, Germany.
augen{at}medizin.uni-leipzig.de
|
References
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Abstract
Introduction
