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RETINAL DISORDERS
The novel use of decorin in prevention of the developmentof
proliferative vitreoretinopathy (PVR)
Khaled Nassar & Julia Lüke & Matthias Lüke & Mahmoud
Kamal & Effat Abd El-Nabi &Mahmoud Soliman & Martin
Rohrbach & Salvatore Grisanti
Received: 21 February 2011 /Revised: 21 April 2011 /Accepted: 24
April 2011 /Published online: 7 July 2011# Springer-Verlag 2011
AbstractBackground The cytokine transforming growth
factor-ß(TGF-ß) is a pivotal contributor to tissue fibrosis and
akey cytokine in the pathogenesis of cellular
transdiffer-entiation, epithelial-mesenchymal transition (EMT),
andcell adhesion. This study evaluates the effect of decorin,
anaturally occurring TGF-ß inhibitor, in an experimentalrabbit
model for proliferative vitreoretinopathy (PVR).Methods Traumatic
PVR was induced in 50 rabbits dividedinto ten groups (n=5). One
group (GI) reveals a controlwith no treatment after trauma. Groups
(GII–GIV) con-sisted of subgroups receiving phacovitrectomy at
threedifferent time points; (a) at the time of trauma, (b) 1
week
following trauma, and (c) 2 weeks following trauma. GIIIand GIV
received 100 μg or 200 μg decorin, respectively.PVR severity was
scored from 0 to 4. The amount offibrosis was quantified using
JMicroVision© software.Results The control group GI developed
severe PVR withtractional retinal detachment (TRD); (PVR score ≥2)
in fourrabbits out of five. Vitrectomy had a positive effect
(p<0.05) on PVR development when preformed immediately,however
the developed fibrosis was high. The best resultswere obtained when
surgery was used in conjunction withdecorin that reduced both the
PVR score and fibrosisdevelopment significantly (p
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extracellular matrix (ECM) proteoglycans, known as
smallleucine-rich proteoglycans (SLRPs) [3]. It is composed of
a40-kDa protein core and one chondroitin/dermatan sulfateside
chain. Decorin plays a key role in the regulation ofECM assembly by
binding to several components such ascollagen [4–6], thrombospondin
[7], and fibronectin [8, 9].Interaction of decorin with collagen
has been shown toaffect fibril formation by causing an initial
delay in thelateral assembly and a reduction of the average
fibrildiameter [4, 10]. In addition to its ability to modulate
theECM assembly, decorin also displays a number of biologiceffects
through binding to growth factors such as trans-forming growth
factor beta (TGF-ß) [11, 12] and withconnective tissue growth
factor (CTGF) [13]. Furthermore,it has been demonstrated that
decorin has an inhibitoryeffect on platelet-derived growth factor
(PDGF), anothermajor player in wound healing [14]. Decorin is
alsoinvolved in the control of cell growth by binding to
theepidermal growth factor (EGF) receptor [15], leading
toactivation of mitogen-activated protein (MAP) kinases
andinduction of the growth suppressor p21 [15–17]. Inaddition,
decorin regulates intralysosomal degradation [18].
Proliferative vitreoretinopathy (PVR) is characterized bythe
formation of fibrotic membranes within the vitreous andat the
retina. Contraction of these membranes may causevitreoretinal
traction, traction-related retinal breaks, recur-rent retinal
detachment (RD), and ocular hypotony [19]. Avariety of studies
indicate that PVR is a complex processcomprising events that are
similar to those of the woundhealing response with inflammation,
migration, and prolif-eration of a variety of cells [20, 21].
Different studiessuggest that retinal pigment epithelial cells
(RPE) contrib-ute to fibrosis by epithelial-mesenchymal transition
(EMT)[22, 23]. PVR developed following RD showed detachmentof RPE
from their normal location. Then they either migrateor are swept in
fluid vitreous to the retinal surfaces, wherethey undergo EMT to
form several morphologic typesincluding fibroblast-like cells [22].
TGF-ß is a pivotalcontributor to tissue fibrosis and a key cytokine
in the
pathogenesis of EMT [23]. TGF-ß levels are elevated inPVR
vitreous and they correlate with the presence ofintraocular
fibrosis [24]. Neutralizing TGF-ß antibodieshave been shown to
reduce experimental dermal scarring[25] and have also been
introduced into glaucoma filtrationsurgery [26, 27]. Grisanti et
al. reported the potential use ofdecorin [28] in glaucoma filtering
surgery without evidentocular toxicity. Inspired by these studies,
we wanted toanalyze whether decorin could be used instead of
thepolyclonal antibodies [25] or the more demanding recom-binant
human anti-TGF-ß antibodies [27] to prevent post-traumatic PVR.
The current study evaluated the use of decorin as anadjuvant
anti-fibrotic treatment in a rabbit model of PVR[29]. The rabbit
model was preferred over a primate model[30] because it is well
established, cost-effective, and itsaggressive wound-healing
response makes it equivalent tohigh-risk eyes in humans [31]. The
model involves oculartrauma and vitreous hemorrhage induction. Both
of themare important risk factors for PVR development [32, 33].
Materials and methods
Animals
All experiments were performed with female chinchillabastard
rabbits (Crl:CHB) 3–6 months old and weighing1.5–2.5 kg. The
animals were obtained from Charles RiverLaboratories (Sulzfeld,
Germany) and acclimatized for1 week before the experiments started.
Traumatic PVRwas induced in 50 rabbits equally divided into ten
groups.One group (GI) served as the control and the other
groupsdiffered in the time of surgical intervention
(phacovitrec-tomy) and dosage of decorin (100 μg and 200 μg) that
wasintravitreally injected (Table 1). Principles of
LaboratoryAnimal Care (NIH publication No. 85–23, revised 1985),the
OPRR Public Health Service Policy on the HumaneCare and Use of
Laboratory Animals (revised 1986), and
Group Subgroup na Trauma Vitrectomy time in relation to trauma
IVTb decorin dose
GI - 5 Trauma - -
GII GIIa 5 Trauma Immediate -GIIb 5 Trauma 1 week
GIIc 5 Trauma 2 weeks
GIII GIIIa 5 Trauma Immediate 100 μg /0.1 mlGIIIb 5 Trauma 1
week
GIIIc 5 Trauma 2 weeks
GIV GIVa 5 Trauma Immediate 200 μg/0.1 mlGIVb 5 Trauma 1
week
GIVc 5 Trauma 2 weeks
Table 1 Animal groups
na number of rabbits
IVTb intravitreal
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the U.S. Animal Welfare Act, as amended, were followed,as well
as the current version of the German Law on theProtection of
Animals were applied.
Anesthesia
For anesthesia and sedation, ketamine (Ketanest; Parke
Davis,Berlin, Germany), xylazine (Rompun; Bayer,
Leverkusen,Germany) and local anesthesia with oxybuprocaine
drops(Novesine 0.4%; Novartis, Nürnberg, Germany) were used.General
anesthesia was achieved with intramuscular (IM)injection of 25
mg/kg-body weight ketamine and 2 mg/kg-body weight xylazine, and
after ½ hour, another half dosewas given. Sedation was achieved
with intramuscularinjection of 12.5 mg/kg-body weight ketamine and
1mg/kg-body weight xylazine, and after ½ hour, another halfdose was
given.
Surgical procedure
Due to the impact of the procedure on the visual abilityof the
animal, only the right eyes were treated. Surgerywas performed
under general anesthesia as describedbefore. All surgeries were
done by the same surgeon.Briefly, the pupils were maximally
dilated. Preoperativefundus examination was done to exclude the
presence ofa pre-existing fundus abnormality. Principles of
aseptictechnique and preoperative care were applied and surgerywas
done with the use of an operating microscope (Zeiss
OPMI, Jena, Germany). In all groups, a previouslydescribed
rabbit model of traumatic PVR was used[29]. We have done two
modifications for this model.First, we used a specifically designed
incision marker tostandardize the trauma induction site. Second, we
used amixture of 1% buffered formaldehyde and 1.25% glutar-aldehyde
as a fixation solution for the enucleated eyes.Briefly, while the
specifically designed incision markerwas held in place, an 8-mm
oblique scleral incision wascarried out at a distance of 1 mm and 2
mm behind thelimbus. The incision was performed at the upper
nasalquadrant. The wound was sutured with three interrupted8–0
Vicryl sutures (Ethicon, Johnson and Johnson Intl,Belgium) and 0.4
ml autologous blood was injectedintravitreally (Fig. 1a). In GI,
only this procedure wasdone. In GII, GIII, and GIV; pars plana
vitrectomy wasdone using a vitrectomy machine (Storz, Bausch
andLomb, Berlin, Germany). Vitrectomy was either
preformedimmediately after trauma and wound closure (subgroupsa),
or 1 week (subgroups b) or 2 weeks (subgroups c)thereafter (Table
1). Phacovitrectomy technique wasmodified to adapt to the rabbit’s
ocular anatomy. A lateralcanthotomy was preformed followed by
eyelid speculumapplication. The lens was then emulsified and
aspiratedthrough corneal approach and the corneal wounds
weresecurely sutured. Then two preplaced limbal sutures wereused to
fix a vitrectomy contact lens ring holding a contactvitrectomy
lens. Pars plana vitrectomy was then preformedusing one-step
23-gauge vitrectomy system (D.O.R.C.
Fig. 1 Surgical procedure. aInduction of traumatic PVR:While the
marker (arrow) washeld in place, an oblique scleralincision was
made. Then thewound was repaired followed byintravitreal injection
of 0.4 ml ofautologous blood. b Vitrectomy:Core vitrectomy was done
forremoval of the vitreous hemor-rhage (arrow) and the
developedmembranes. c Posterior vitreousdetachment (PVD): PVD
wasinduced using the vitrectomycutter. While the suction-onlymode
of the foot pedal wasapplied, the posterior vitreous(arrow) was
entangled andcarefully detached from the ret-inal surface. d
Vitreous baseremoval: the retinal peripherywas indented and the
vitreousbase (arrow) was removed. Theretina was examined for
thepresence of tears or detachment
Graefes Arch Clin Exp Ophthalmol (2011) 249:1649–1660 1651
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Deutschland GmbH, Berlin, Germany). Sclerotomies werefashioned
1.5 mm from the limbus. Vitrectomy wasperformed at high cutting
rate 750 cuts/min and lowaspiration 150 mmHg (Fig. 1b). The
aspiration wasreduced when getting closer to the retina and
posteriorvitreous detachment was attempted (Fig. 1c).
Retinalperiphery was then indented and the vitreous baseremoved
(Fig. 1d). In groups with immediate vitrectomy,the infusion cannula
was applied before the induction oftrauma to maintain adequate
intraocular pressure (IOP) foreasy scleral incision and suturing.
The infusion was closed
at the time of blood injection. The procedure was stoppedfor 20
min to allow the blood to coagulate. At the end ofthe surgery, the
retina was examined for the presence ofretinal breaks or
detachment. The number of the iatrogenicretinal breaks was
recorded. If the retina was attached, notamponade was used. In the
presence of retinal breaks,only fluid–air exchange was done. The
sclerotomies wereclosed followed by closure of the conjunctiva and
thelateral canthotomy. At the end of the surgery, an antibioticeye
ointment (Refobacin®; Merck KgaA, Darmstadt,Germany) was applied
once daily and continued for a
1652 Graefes Arch Clin Exp Ophthalmol (2011) 249:1649–1660
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week. The anterior segment and the fundus were examinedat weekly
intervals (Fig. 2a).
Preparation and administration of decorin
Decorin (D-8428; Sigma-Aldrich, Steinheim, Germany)was dissolved
in phosphate buffered saline (PBS)(0.5 mg/0.25 ml). The drug was
diluted to reach a finaldose of 100 μg/0.1 ml, in GIII and 200
μg/0.1 ml, in GIV.A 30-gauge needle was used to inject 0.1 ml
intravitreallyafter the vitrectomy was completed.
Histopathological examination
On the 30th post-vitrectomy day, while the animal wasunder
general anesthesia, the right eye was enucleated. Adose of 0.3
ml/kg T-61 (a combination of embutramide,mebenzoniumiodide, and
tetracaine hydrochloride; HoechstRoussel Vet, Frankfurt, Germany)
was then injected throughthe intracardiac route. The whole eye was
fixed for 36–48h in a mixture of 1% buffered formaldehyde and
1.25%glutaraldehyde. The eyes were then processed for staining
with hematoxylin and eosin and Masson’s trichrome stainsas
previously described [34].
Photographs
A consistent clinical observation of the fundus was notpossible
in all animals due to media opacities as cataract,vitreous
hemorrhage, the development of fibrous ingrowth,the development of
postoperative iritis, and poorly dilatedpupils. A detailed and
reliable anatomic evaluation wastherefore preformed on the
enucleated eye under an operatingmicroscope (Zeiss OPMI, Jena,
Germany). Clinical and grosspathology findings were recorded with a
camera (Sony CCD,DXC-107, Tokyo, Japan) attached to the operating
micro-scope. Photographs were then captured from the video
recordswith ACDSee Pro software version 8.1 (ACD system,
Ltd,British Columbia, Canada). The external appearance of thesite
of the trauma was first documented. The eyes weresectioned through
the midpoint of the wound. The resultedcalottes were examined and
photographed. Histological speci-mens were examined and documented
with inverted micro-scope (Leica DMI 6000 B microscope, Wetzlar,
Germany).Photos were captured using a DFC 290 compatiblecamera and
the appropriate software (Leica ApplicationSuit LAS Software,
Wetzlar, Germany).
Image analysis for fibrosis evaluation
The severity of PVR was staged into five stages based onthe
grading system described by Cardillo et al. [35](Fig. 2b–f).
Photographs of the external appearance of thepost-traumatic wound
were evaluated and the maximumwidth of the healed wound was
calculated with the 1Dmeasurement tool of the software
(JMicroVision©, Univer-sity of Geneva) as previously described [36]
(Fig. 2g). As apreparatory step for morphometric analysis of
fibrosis,Masson's trichrome stain was used to distinguish cells
fromsurrounding connective tissue. Collagen fibers of theconnective
tissue were stained blue. A careful morphomet-ric analysis of
developed fibrosis at the site of the woundwas carried on three
randomly selected 640× photographs.Photographs were analyzed with
the Magic Wand tool ofthe same software. Areas stained in blue were
selectedbased on pixels similarity then measurements for the
area(μm2) were calculated [36] (Fig. 2h and i).
Statistical evaluation
Statistical analysis was performed using SPSS 16 software(SPSS
Inc, Chicago, IL, USA). Descriptive analysis for theresults was
reported as the median and the interquartilerange for
non-parametric parameters, and as mean andstandard deviation for
parametric one. The Mann–Whitney
Fig. 2 PVR score and fibrosis assessment. a Clinical evaluation
(GI,case number 2): Fundus examination revealed PVR development
PVRstage 3 (large arrow) with traction over the medullary ray
(smallarrow). b PVR stage 4 (GI, case number 4): 100% of the retina
wasdetached associated with a closed funnel configuration.
Fibrousingrowth (arrow) was severe, with obvious dragging of the
retinacausing prominent retinal folds with viscous subretinal fluid
formation(star). The lens was cataractous and pushed anteriorly by
the fibrousmembrane. c PVR stage 3 (GIIc, case number 3): Between
50 and100% of the retina (large arrow) was detached (severe
retinaldetachment), associated with an open-funnel configuration
(smallarrows). Fibrous ingrowth from the wound was severe. A
viscoussubretinal fluid (star) was formed. In this case, 100% of
the retina wasdetached. d PVR stage 2 (GIIIc, case number 4): Up to
50% of theretina was detached (moderate tractional elevation),
usually directlysurrounding the ray (arrows). Prominent fibrous
ingrowth was present,with faint bands connecting the peripheral ray
fibrous mass to the discor ray. In this case, detachment was
minimal and confined to themedullary ray. e PVR stage 1 (GIIIb,
case number 2): The retina isattached with minimal traction
elevation confined to the medullary ray(arrows). f PVR stage 0
(GIVb, case number 2): Attached retina(arrows) without evidence of
fibrous ingrowth. g Estimation of theexternal wound breadth (GI,
case number 2): The maximum breadth(mark) of the healed wound
(arrow) was calculated with the 1Dmeasurement tool of the software
(JMicroVision©, University ofGeneva). h Estimation of the developed
fibrosis at wound site (a)(GIIc, case number 3): As a preparatory
step for morphometricanalysis of fibrosis, Masson's trichrome stain
was used to distinguish-ing cells from surrounding connective
tissue. Collagen fibers of theconnective tissue were stained blue
(arrow). i Estimation of thedeveloped fibrosis at wound site (b)
(GIIc, case number 3): Amorphometric analysis of developed fibrosis
at the site of the woundwas carried on 640× photographs.
Photographs were analyzed withthe Magic Wand tool of the software
(JMicroVision©, University ofGeneva). The color tolerance was
adjusted to include a wide range ofthe blue color intensity and
then these different degrees were mergedand the total area (arrow)
was calculated (μm2)
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Fig. 3 Effects of the adjuvant intravitreal use of decorin
followingvitrectomy. a PVR stage 0 (GIVa, case number 4): The
retina (whitearrows) was completely attached. Minimal fibrous
strands were seenover the medullary ray (black arrow). b PVR stage
0 (GIVb, casenumber 5): The retina (white arrows) was completely
attached withoutevidence of fibrous traction. The medullary ray
showed no fibroustraction (black arrow). c Attenuated fibrous
ingrowth (GIIIa, casenumber 2): Fibrous ingrowth entangling blood
(large white arrow)was seen arising from the site of trauma (small
white arrow). Theingrowth was markedly attenuated and extends to
the remains of thelens (star). d Attenuated PVR (GIIIc, case number
1): Fine fibrousstrands (white arrows) were seen stretched between
small retinal folds(black arrows). e PVR formation in the presence
of retinal tears,(GIIIb, case number 4): The retina (white arrows)
was partially
detached despite the presence of a retinal break (black arrow),
aviscous subretinal exudates (star) was formed. f PVR formation in
thepresence of retinal tears, (GIVc, case number 1): The retina
(whitearrows) was completely attached in spite of the presence of
retinalbreak (black arrow). No PVR reaction was detected. g
Estimation ofthe external wound breadth (GIV, case number 2): The
maximumbreadth (mark) of the healed wound (arrow) was calculated
with the1D measurement tool of the software (JMicroVision©,
University ofGeneva). h Estimation of the developed fibrosis at
wound site, (GIIIc,case number 3): Collagen fibers of the
connective tissue were stainedblue (black arrow). i Estimation of
the developed fibrosis at woundsite (b), (GIIIc, case number 3):
Measurement of the fibrous area(arrow) using the Magic Wand tool of
the software (JMicroVision©,University of Geneva)
1654 Graefes Arch Clin Exp Ophthalmol (2011) 249:1649–1660
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non-parametric test was used to compare median values
ofdifferent variables between groups. For all tests, the level
ofsignificance was set at p
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kidney [45], lung [46], cerebral [47], and muscular
fibrosis[48]. In ocular diseases, decorin was evaluated as
anti-fibrotic agent following glaucoma filtering surgery [28].
Arecent study showed that decorin gene transfer effectivelyprevents
TGF-ß driven transformation of keratocyte andcorneal fibroblast to
myofibroblasts [49].
Because the mechanisms involved in the pathogenesis ofPVR may
differ in rhegmatogenous RD compared totrauma, specific PVR animal
models of ocular penetratingtrauma have been developed in non-human
primates [30,50, 51] and rabbits [29, 32, 52, 53]. These models
allow theevaluation of complicated ocular injury in a
controlledmanner to elucidate mechanisms of injury, cellular
prolif-eration and tractional forces leading to TRD and PVR. Wehave
used a previously described rabbit model of traumaticPVR [29, 52].
In this study, two modifications wereintroduced to the used model
to improve its reliability.First, with standardized oblique scleral
incision, the modelwas able to produce constant severe forms of PVR
andTRD, which simulate the human condition (Fig. 2b).Second, we
used a fixation mixture of (1% bufferedformaldehyde/1.25%
glutaraldehyde for 36–48 h) for fixing
whole eyes. This solution resulted in minimal volumecontraction
without compromising cellular preservation[54]. Consequently, the
reliability of the results wasimproved. In turn, it avoided the
inconsistency of observa-tions based on clinical fundus
examination. As demon-strated in control group GI, the model was
effective andreliable. Clinical landmarks describing the
progression ofexperimental PVR have been divided into those
thatfeature a model using an intact vitreous [55–57] andthose that
include compressed vitreous as a step in thedevelopment of PVR
[58]. However, both classificationsdescribed the developed PVR in
vivo non-traumaticrabbits PVR models and do not fit to describe our
results.To overcome this problem, a PVR scoring system based onthe
natural history of penetrating ocular trauma in rabbitwas used [32,
35, 52]. A PVR stage of 1 or less was usedto indicate effective
treatment.
The multiple features of acute ocular injury make it
verydifficult to interpret retrospective data regarding the
mostappropriate timing for surgical intervention [59–62].Performing
vitrectomy under fixed experimental conditionsallows better
understanding of the outcome. Cleary and
Table 4 Comparison between decorin-treated groups and the
control group
GI and GIIIa GI and GIIIb GI and GIIIc GI and GIII GI and GIVa
GI and GIVb GI and GIVc GI and GIV
PVR score 0.033* 0.013* 0.049* 0.005* 0.009* 0.003* 0.05*
0.001*
Wound size 0.009* 0.175 0.117 0.021* 0.009* 0.009* 0.009*
0.001*
Fibrosis area 0.009* 0.016* 0.016* 0.002* 0.016* 0.016* 0.047*
0.005*
*Significant p value, (Mann–Whitney test)
Table 3 Descriptive analysis of the different evaluation
parameters
Retinal breaks PVR score Wound width (μm) Fibrosis area
(μm2)
M P M P Mean SD Mean SD
M 25 75 M 25 75
GI 0 0 0 3 1.5 3.5 68 17 5,734 603
GIIa 0 0 2 0 0 2 78 13 9,639 2,470
GIIb 0 0 1 3 2 3 68 12 6,180 1,062
GIIc 0 0 1.5 3 2 4 58 18 6,924 825
GII 0 0 2 3 0 3 68 16 7,581 2,151
GIIIa 2 0 2.5 1 0 2 101 9 2,313 319
GIIIb 0 0 1 0 0 1 81 9 3,355 1,250
GIIIc 0 0 1 0 0 2 91 16 4,389 565
GIII 0 0 2 0 0 1 91 14 3,352 1,156
GIVa 0 0 0 0 0 0 186 31 2,335 1,910
GIVb 0 0 2 0 0 1 176 14 4,279 594
GIVc 1 0 1.5 1 0 2 209 17 4,572 437
GIV 0 0 2 0 0 1 190 25 3,729 1,501
PVR proliferative vitreoretinopathy, M median value, P
percentiles, SD standard deviation
1656 Graefes Arch Clin Exp Ophthalmol (2011) 249:1649–1660
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Ryan used such a model to evaluate vitrectomy inexperimental
posterior penetrating eye injury in the rhesusmonkey [51].
Cryopexy, scleral buckling, and sulfurhexafluoride tamponade were
used when indicated. Theyconcluded that vitrectomy at 1 or 14 days
after traumasignificantly prevents TRD. In the current study, we
choseto combine this traumatic PVR model and 23-gauge pars
plan vitrectomy. The use of 23-gauge vitrectomy greatlyshortens
the procedure time. However, the trocars should beobliquely
inserted to prevent the instability of the vitrectomycannulas
caused by thin rabbit’s sclera; as well as to improvethe sealing of
the wounds. In our study, no retinopexy,buckling, or internal
tamponade except for air were used. Wetried to limit the number of
the factors that might influence the
Fig. 4 Histopathology. a Fi-brous reaction following trauma(GI,
case number 1): The lenshas been lost during processing.Fibrous
proliferation (large arrow)from the wound (star) appears tobe
derived mainly from the uvealtract. The retina (small arrow)
isdrawn up to the wound by thisfibrous proliferation. The
fibroustissue was in the process offorming a cyclitic
membrane(Masson’s trichrome stain, 50×). bFibrous reaction
following trauma(GI, case number 3): Another eyeshowing severe PVR
develop-ment after injury. The wound(star) is organized and has
bloodvessels and scattered pigment inthe fibrous tissue (large
blackarrow). A marked fibrous prolif-eration extends inwards from
thewound and swirls of fibrous tissueform a plaque on the surface
ofthe retina (long arrow), (Masson’strichrome stain, 50×). c
Fibrousreaction following decorin treat-ment (GIIIb, case number
2): Aweak fibrous proliferation (largearrow) extends inwards from
thewound (star). The adjacent retina(small arrow) was seen
attached(Masson’s trichrome stain, 50×). dAborted PVR formation
(GIIIa,case number 4): An epiretinalmembrane was present with
min-imal collagen deposition (arrow)while the retina was
attached(star) (Masson’s trichrome stain,100×). e Attached retina,
(GIIIb,case number 5): Low magnifica-tion image of the retina
(arrow)showed perfectly attached retinawith preserved architecture
(Mas-son’s trichrome stain, 50×). fNormal photoreceptor layer:
Ahigh magnification image of theretina showed preserved details
ofthe outer nuclear layer (whitearrow) and the retinal
photore-ceptors layer (black arrow). Thephotoreceptors–retinal
pigmentepithelium relationship was pre-served (Masson’s trichrome
stain,1,600×)
Graefes Arch Clin Exp Ophthalmol (2011) 249:1649–1660 1657
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outcome, thus a real evaluation of the given treatment couldbe
achieved. We found that vitrectomy done immediatelyfollowing trauma
at the end of the follow-up time significantlyreduced the PVR score
compared to the control (p
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The novel use of decorin in prevention of the development of
proliferative vitreoretinopathy
(PVR)AbstractAbstractAbstractAbstractAbstractIntroductionMaterials
and methodsAnimalsAnesthesiaSurgical procedurePreparation and
administration of decorinHistopathological
examinationPhotographsImage analysis for fibrosis
evaluationStatistical evaluation
ResultsEffects of trauma (GI)Effects of vitrectomy as single
treatment (GII)Effects of adjuvant decorin therapy (GIII and
GIV)Histopathology
DiscussionReferences