Download Early morphogenesis of persistent hyperplastic tunica

Investigative Ophthalmology & Visual Science, Vol. 29, No. 7, July 1988
Copyright © Association for Research in Vision and Ophthalmology
Early Morphogenesis of Persistent Hyperplostic Tunica
Vasculosa Lentis and Primary Vitreous
The Dog os on Onrogeneric Model
Michael H. Boeve,* Tineke von der Linde-Sipmaaf and Frans C. Srodes*
Observations on (postnatal) persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic
primary vitreous (PHTVL/PHPV) in man and dog have been published previously. Up to the present,
no evidence on the etiology of this entity was available. The hereditary occurrence of the disease in the
Dobermann pinscher dog and the similarity of ocular development in mammals has provided a useful
model in providing ontogenetic data. The present study deals with the early morphogenesis of
PHTVL/PHPV, from day 25 to 44 post-coitum (D25-D44), in genetically affected dog fetuses.
Normal beagle dog fetuses served as reference material, which has been described separately. At D30,
the hyaloid system, including the tunica vasculosa lentis posterior, had developed further than in the
reference fetuses. From that stage onward, a retrolental fibrovascular membrane developed. In some of
the eyes of D37, posterior polar subcapsular cataracts and preretinal glial proliferations were observed. Capsular anomalies and distortions of the lens shape as seen in clinical PHTVL/PHPV were
not observed, and are believed to be secondary entities. Extrapolation of some of the obtained data
from dog to man is possible by the use of comparable gestational time scales. The anterior form of
(PHTVL/PHPV) in man probably develops its main features in the period of approximately 43 to 66
days of pregnancy. Recently, anti-angiogenetic properties of normal vitreous have been described.
This, and the fact that overdevelopment and subsequent incomplete regression of the hyaloid system
plays a major role in the pathogenesis of PHTVL/PHPV, gives rise to the hypothesis that a changed
amount or effectiveness of such (humoral) factors is an important factor in the etiology of this disease.
Invest Ophthalmol Vis Sci 29:1076-1086,1988
The anterior form of persistent hyperplastic tunica
vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV) is a congenital eye anomaly, in
most cases leading to cataract. The occurrence of this
entity has been described in man and in dogs.
In man, over 200 cases, mainly unilateral and supposedly nonhereditary, have been described under
different names.1 The entity can be distinguished into
an anterior and a posterior form.2"4
The first description of PHPV in a dog was published by Grimes and Mullaney in 1969,5 and confirmed by other case reports as summarized by
Stades.6 Only in recent years has the frequent occur-
rence of PHTVL/PHPV been described in specific
dog breeds, at first in the Dobermann pinscher6 and
lately also in the Staffordshire bull terrier.7-8 Clinical,6
surgical,9 pathological10 and genetic" aspects of the
disorder have been described for the Dobermann
pinscher; in this breed a hereditary basis of the disease
was demonstrated.''
The close resemblance of the clinical manifestations in man and dog, as well as the frequent (inherited) occurrence of PHTVL/PHPV in the Dobermann pinscher breed provide a useful model for research on the ontogenesis. In addition, the high
degree of similarity in development of the eye in different mammals12"15 allows extrapolation of some of
the results of this study to PHTVL/PHPV of man.
The embryonic and neonatal development of the
normal canine eye13 and the early morphogenesis of
the lens, lens capsule, hyaloid system and vitreous in
particular have been described.16 On the ontogenesis
of PHTVL/PHPV only one preliminary communication17 has been published. The present study was undertaken to establish when and how the morphogen-
From the *Small Animal Clinic and the fDepartment of Pathology, Faculty of Veterinary Medicine, University of Utrecht,
Utrecht, The Netherlands.
Submitted for publication: November 17, 1987; accepted January 18, 1988.
Reprint requests: Michael H. Boeve, DVM, Small Animal
Clinic, University of Utrecht, Yalelaan 8, 3584 CM Utrecht, The
Netherlands.
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EARLY MORPHOGENESIS OF PHTVL/PHPV / Doeve er ol.
esis of the eye in genetically PHTVL/PHPV-affected
dog fetuses becomes aberrant.
Materials and Methods
Table 1. The average diameters (AD) of the eyes (n)
of genetically PHTVL/PHPV-affected Dobermann
pinscher fetuses, from D25 to D44 (values are
given in millimeters)
Fetuses
From matings of severely (grade 2-6) PHTVL/
PHPV-affected Dobermann pinschers, 41 fetuses
were collected at ages of 25, 28, 30, 33, 35, 37 and 44
days post-coitum (D25-44). The amounts per age are
stated in Table 1. Sixty-eight of the obtained eyes
were available for this study. The fetuses were collected as previously described.16 Seventeen fetuses
D25
D28
D30
D33
D35
D37
D44
(n)
AD
Min
Max
(14)
0.284
0.618
0.747
1.43
2.20
2.56
0.275
0.598
0.675
1.35
2.08
2.37
3.5
0.294
0.631
0.830
1.49
2.46
2.73
(4)
(10)
(10)
(4)
(14)
(12)
3.7
3.9
Fig. 1. D25; optic cups. Transverse sections; overall views. H &
E; X25. (LV = lens vesicle; HA = hyaloid artery; R = retina; SE
= surface ectoderm). (A) The lens vesicle is still open. A clump of
cells from the surface ectoderm (epitrichia) is present (arrow). (B)
The lens vesicle is closed, but still attached to the surface ectoderm.
Some loose epitrichial cells are present (arrows), (C) The lens vesicle is closed and detached from the surface ectoderm. The annular
vessel (A V) at the anterior edge of the optic cup is present.
e
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«•*•
Fig. 2. D30; equatorial
region of the lens. Capillaries (arrows), connect the anterior and posterior portion
of the tunica vasculosa
lentis. (R = retina; PLF
= primary lens fibers). PAS;
X40.
25
2 I
from normal beagle parents, with ages up to D35,
served as reference material. The results of that study
have been published separately.16
In order to minimize the variation of gestational
ages, matings were carried out as soon as possible
after ovulation, as determined by plasma progesterone measurements.16
Animal care and treatment in this study were in
compliance with the ARVO Resolution on the Use of
Animals in Research.
(Fig. 1 a-c). In eight eyes the process of invagination,
by which the lens vesicle is formed, had not yet been
completed and the anterior central part of the lens
vesicle was still open (Fig. la). In these eyes, a clump
of epitrichial cells was present at this location. In four
eyes the lens vesicle had closed (Fig. lc); in two of
these it was still attached to the surface ectoderm (Fig.
lb). In most sections, the cavity of the closed lens
Histology
Following collection and death of the fetuses, the
heads or the eyes alone were fixed in 4% buffered
formaldehyde, processed and stained as described before.16 Because of damage to some of the D28 material, a few 1 jtm sections of specimens fixed and embedded for electron microscopy were stained with the
periodic acid-Schiff (PAS) reaction. The development of all eyes was examined by light microscopy.
The average diameters of the fetal eyes were measured according to a previously described method.16
Results
Optic Cup
Throughout this study, the eyes at all ages were
round to oval, double-layered structures. The average
diameter values of the eyes of D25 up to D44 showed
a steady increase from 0.284 to 3.7 mm (Table 1).
Lens
At D25, the lens vesicles consisted of epithelial
cells, and had a rounded to somewhat conical shape
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Fig. 3. D33; transverse section; overall view. A fibrovascular
membrane (arrows) is present retrolentally. The peripheral detachment appears artificial (see also Fig. 8). Sections of hyaloid vasculature are not present within the vitreous (V). (L = lens; R = retina; N
= optic nerve). H & E; X4.
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vesicles contained some amorphous and cellular
(epitrichial) material.
At D28, the primary lensfibers,formed by elongation of the posterior cells of the lens vesicle, had filled
the posterior half of the lens vesicle.
At D30, the lens vesicles were almost obliterated by
the primary lensfibers,thus leaving a flat cavity anteriorly (Fig. 2). From this developmental stage onwards the lens sphere was oval.
At D33 (Fig. 3) the flat cavity as at D30 was barely
detectable in most specimens.
At D35 (Fig. 4) the lens spheres were obliterated.
At D37 posterior polar subcapsular cataracts were
observed in two of the eyes (Fig. 5).
At D44, a small posterior polar subcapsular cataract was observed in one lens.
Lens Capsule
At D25, the anlage of the lens capsule was observed
as a very thin basement membrane-like layer of
faintly PAS-positive material, surrounding the lens
vesicle. The histologic appearance of this layer was
similar to that of thefibrillarcontents of the primitive
vitreous.
At D28, the lens capsule was observed as a faintly
stained, straight and continuous structure (Fig. 6).
At D30, the posterior part of the capsule, as well as
the equatorial region, where the vasculature of the
tunica vasculosa lentis (TVL) was very well developed, PAS-positive and lying in close proximity to
the capsule, was thicker than the anterior part.
From D33 onward, except in some eyes at D37 and
D44, the capsule had a wrinkled appearance.
Fig. 5. D37; posterior part
of the lens (L), the lens capsule (LC) and anterior part
of the plaque (P). A posterior polar subcapsular cataract is present (arrows). (H
= main ramification of hyaloid artery; Tp = capillary of
tunica vasculosa lentis).
PAS; X40.
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0.5 mm
Fig. 4. D35; transverse section; overall view. The posterior lens
capsule is completely covered by afibrovascularplaque (arrows). (L
= lens; V = vitreous; R = retina). PAS; X2.5.
Vascular System
At D25 (Fig. la-c), a short and straight hyaloid
artery was present in all eyes. No indication of a ramification of the hyaloid artery into vasa hyaloidea propria or the future tunica vasculosa lentis posterior was
observed. The annular vessel at the distal edge of the
optic cup was present.
In the D28 material, numerous cross-sections of
vessels of the hyaloid-TVL system were observed.
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Fig. 6. D28; posterior part
of the lens (L), the lens capsule (LC) and capillary of
the tunica vasculosa lentis
posterior (Tp). Cell (c)
might be a pericyte or a
primitive fibroblast, indicating a first onset of the retrolental membrane. Hy
= hyalocyte. PAS; XI00.
i
Hy
TVL vasculature was present, positioned directly
against the lens capsule (Fig. 6).
At D30 (Fig. 7), sections through vessels of the
hyaloid-TVL system were more numerous than in
the reference material.15 Predominantly in the central
region, a proliferated layer of TVL vasculature was
located against the posterior lens capsule, covering
that region almost completely. The vascularization of
the anterior side of the lens was similar to the normal
controls. This vasculature was connected with the
TVL posterior by capillaries in the equatorial region
of the lens.
At D33 a distinct but thin retrolental fibrovascular
layer, which characterizes PHTVL/PHPV postnatally, was present in all eyes (Figs. 3, 8). In these
plaques, cross-sections of the TVL vasculature were
present. At this stage, the central part of the plaque
was locally attached to the posterior lens capsule (Fig.
3). At the periphery, the plaque was detached from
the capsule. Still, capillaries and cellular components,
including fibroblasts, were in contact with the capsule
(Fig. 8). Cross-sections through the vasa hyaloidea
propria in the vitreous space were less numerous than
at D30 (Figs. 3, 7).
Fig. 7. D30; transverse
section of the vitreous. The
hyaloid-TVL system is very
well developed. (L = lens;
Hp = vasa hyaloidea propria; Tp = tunica vasculosa
posterior; R = retina). H &
E; X25.
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Fig. 8. D33; peripheral
part of the posterior lens
capsule (LC) and retrolental
fibrovascular membrane
(P), which has (most probably as an artefact) been detached. (L = lens). See also
Figure 3. PAS; X40.
8
From D35 (Fig. 4) onward, a plaque, completely
attached to the posterior lens capsule, was observed in
all eyes. The central thickness of the plaques ranged
from 29.0 to 45.1 (mean 37.9) ^m. Except for the
main trunk of the hyaloid artery, no vasa hyaloidea
propria were present in the vitreous space.
At D37, the central thickness of the plaques was
45.1 to 119.1 (mean 73.4) fim. Many cross-sections of
TVL and hyaloid vasculature were present within the
plaques (Figs. 5, 9). Except for a straight main trunk
of the hyaloid artery, no parts of the hyaloid system
were found in the vitreous space (Fig. 10). Glial tissue
was observed for the first time in the plaques, but no
melanocytes were observed. At D44 (Fig. 11), the
Fig. 9. D37; magnification of the retrolental
plaque (P). Fibrovascular
tissue, with an embedded
capillary of the hyaloidTVL system (Hs). (L = lens;
LC = lens capsule; V = vitreous). PAS; X40.
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appearance of the anomalies was similar to that at
D37 (Figs. 5, 9, 10). The central thickness of the
plaques varied from 22.5 to 157.8 ^.m (mean: 95.4;
median value: 106.3 pm). In 11 plaques varying
numbers of melanocytes were present. The thinnest
plaque did not contain any melanin-containing cells.
Vitreous
At D25 (Fig. la-c), the primitive vitreous contained some amorphous and fibrillar material but
very few cellular components.
At D28, apart from the vascular elements as described above, the vitreous space contained cells with
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INVESTIGATIVE OPHTHALMOLOGY b VISUAL SCIENCE / July 1988
\
10
"empty" image, ie, a few loose cells within a randomly oriented, seemingly fibrillar matrix.
At D37, a proliferation of neuroglial tissue, intimately attached to and originating from the retina,
was present in four eyes (Fig. 12a, b). These proliferations, followed by serial sections, protruded into the
vitreous and reached the retrolental plaque in three of
these eyes. The thickness of these strands varied substantially; the average size was about 50 jum. In these
three eyes, as well as in six others, additional, very
thin strands of neuroglia were present (Fig. 13a, b).
These originated from the retrolental plaque, extended into the vitreous and connected with a larger,
retina-derived proliferation (Fig. 12a, b), if such was
present.
At D44 (Fig. 11) the vitreous showed a concentration of cells (fibroblasts, hyalocytes) in the proximity
of the plaque.
Retina and Pigment Epithelium
Fig. 10. D37; transverse section. A retrolental, fibrovascular
plaque is present (arrows). The vitreous does not contain sections
of hyaloid vasculature). (L = lens; V = vitreous; R = retina; c
= cornea; Li = eyelid). H & E; X2.5.
the cytological characteristics of fibroblasts and hyalocytes (Fig. 6) amidst an amorphous and slightly fibrillar ground substance.
At D30 (Fig. 7), both the vascular and cellular
components of the primitive vitreous of the affected
fetuses had developed further than those described in
the corresponding reference material.16
From D33 onward (Figs. 3, 4, 10, 11) the absence
of vasa hyaloidea propria gave the vitreous space an
Up to D35 the development of the neural retina
and the pigment epithelium did not differ from that
described in the reference material.16 Apart from the
aforementioned glial tissue, a conical proliferation of
glial tissue was present at the anlage of the optic disc
in five eyes of D37.
In eight of the D44 eyes, the primitive optic disc
contained a similarly shaped mass of glial tissue
(Fig. 14).
Discussion
This study has demonstrated a first, marked difference in embryonic development of PHTVL/PHPV-
Fig. 11. D44; transverse
section of the plaque (P).
The cellular components of
the vitreous are concentrated in the proximity of
the plaque. (L = lens; LC
= lens capsule; V = vitreous). PAS; X20.
11
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50 p
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EARLY MORPHOGENESIS OF PHTVL/PHPV / Doeve er ol.
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0.1mm
Fig. 12. D37; section of
the peripheral retina (R)
and vitreous (V). (A) and
(B) are sections from the
same eye. (A) Proliferation
of glial tissue (G), deriving
from the retina into the vitreous. (B) Section, parallel
to A, showing the glial tissue
(G) continuing as a strand.
(L = lens). Both H & E;
X10.
affected and normal canine eyes at D30. From this
stage onward the (mesodermal) hyaloid-TVL vasculature is the main structure involved in the development of the anomaly. From D37 neuroglia, an ectodermal component, has also been found to participate.
Optic Cup
In the dog, microphthalmia is a less common feature of PHTVL/PHPV than in man. The measurements of the optic cup's average diameter values
(Table 1) did not differ significantly from those of the
reference material.16 For a statistical evaluation of
these values, larger numbers would be required.
Lens
As the eyes of D25 were from fetuses from the same
litter, the differences in closure and separation of the
lens vesicles must be due to slight differences of developmental stage.
Up to D35, the development of the lens was analogous to that described in the reference material.16 At
D37 and D44, some posterior polar subcapsular cataracts were observed in the present material. The localization of these cataracts corresponds with the site of
their onset in PHTVL/PHPV-affected patients.1'6-10
Abnormal lens shapes, such as lenticonus, microphakia or colobomas were not observed.
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Lens Capsule
The morphological features of the posterior lens
capsule were normal, although frequently wrinkled
due to shrinkage, which was also the case in the reference material.16 Recently there has been some discussion as to whether the changes in the posterior lens
capsule—as seen in postnatal PHTVL/PHPV10—
should be regarded as primary or secondary.18 Up to
this moment, changes in the posterior lens capsule,
varying from dissolution to capsular tears, have only
been seen in severely affected patients.110 This suggests that the development of the frequently found
lenticonus posterior10 either is a secondary event, or
these matings failed to produce the most severe cases
that were clinically found in man and dog.1'610
Vascular System
Until D30, the development of the vascular structures of the optic cup matched that described in the
reference material.16 From D30 onward the retrolental part of that vasculature, the hyaloid system (predominantly the vasa hyloidea propna and the TVL
posterior), showed signs of an increased development
and subsequent incomplete regression. The peripheral detachment of the plaque at D33 appears to be
an artifact due to the histologic processing (Fig. 8).
Vitreous has been reported to inhibit angiogen-
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INVESTIGATIVE OPHTHALMOLOGY b VI5UAL SCIENCE / July 1988
Fig. 13. D37; transverse,
serial sections of the retrolental plaque (P) from the
same eye. (A) A thin strand
of glia derives from the
plaque (arrow). (B) Section,
parallel to (A), showing the
continuation of the same
glial strand (arrow) into the
vitreous. (V = vitreous).
Both H & E; X40.
13a
13b
esis.19'20 Impaired or defective anti-angiogenetical
properties of the (secondary) vitreous might be the
cause of the described overdevelopment of intravitreal vasculature in PHTVL/PHPV.
Vitreous
From D33 the vitreous space showed cross-sections
through the main stem of the hyaloid artery only. Its
ramifications had become enbodied in the retrolental
plaque. This situation gave the vitreous space its
"empty" appearance, compared to the reference material of this age group.
Thefibrillarappearance of the ground substance is
probably due to coagulative artifacts due to fixation
technique, as has been described previously.1216 The
fact that the D28 material does not show this coarsefibered structure supports this assumption, because it
had been (differently) prepared for electron microscopic purposes.
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25 JJ
Glial Tissue Proliferations
Reference eyes did not contain glial proliferations
as were observed in the present material.
In his pathologic studies concerning human eyes
with (PHTVL/)PHPV, Manschot2 made special reference to preretinal glial proliferation as a pathologic
characteristic of the entity. He described both larger
and smaller, fibered and cellular preretinal proliferations in infant eyes with (PHTVL/)PHPV. The fibers
of many of these cells were observed to merge into the
fibers of Mueller cells of the retina. Consequently, the
probable neuroglial origin of these structures was
postulated.
In the eyes described here, preretinal glial proliferations (Fig. 13a, b), mimicking those described by
Manschot in man,2 were observed in nine eyes at D37
and D44. The finding of glial tissue in the plaques of
these dog fetuses and in the plaques of (PHTVL/
PHPV-affected) postnatal dogs10 and in man2 sug-
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EARLY MORPHOGENESIS OF PHTVL/PHPV / Doeve er ol.
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gests that this material derives from the glial proliferations described here.
Apart from the glial proliferations described above,
in some eyes there was a small, conical proliferation
of glial cells in the center of the presumptive optic
disc (Fig. 14). A cone-shaped mass of cells of this kind
in postnatal eyes is known as "primitive epithelial
papilla" or "Bergmeister's papilla," and is a frequent
finding in PHTVL/PHPV in man and dog.
Retina and Pigment Epithelium
The general development of the sensory retina and
pigment epithelium in affected eyes was similar to
that in the reference fetuses, except for the cases in
which a neuroglial proliferation was present.
In the contemporary literature, the most current
term for the described anomaly in man is "PHPV."
However, other names have been used in the past,
such as persistent hyperplastic tunica vasculosa lentis
(PHTVL), pseudophakia fibrosa, membranous cataract leucocoria, pseudoglioma and cataracta congenita vasculosa.'' The differences in nomenclature suggest a lack of knowledge about the development of
the anomalies.
Stades6 used PHTVL primarily, and PHPV secondarily, as names for the disease, as the anomaly appeared to be first of all a persistence and hyperplasia
of the TVL posterior. Depending on whether or not
the hyaloid system is considered a part of the primitive vitreous and according to the classical embryologic views, the name PHPV would suggest that the
retrolental tissue proliferations which are pathognomonic for the condition are solely or mainly of ectodermal origin. However, the results of this and other
studies14"16'21 ai indicate a primarily mesodermal origin, although neuroectodermal involvement (the
presence of neuroglia) can be demonstrated in some
cases. Thus the present study supports the name
PHTVL/PHPV, as proposed by Stades,6 although a
shorter name would be preferable for clinical use.
The results of this study give lead to the following
hypothesis about the genesis of (PHTVL/)PHPV in
man. The major visible embryological derangements
in PHTVL/PHPV in the dog occur during the gestational period of D30 to D45. This developmental period extends from the obliteration of the lens vesicle
until the first signs of regression of the hyaloid system. Extrapolating this to the human embryo and
taking the difference in time of ocular development
in pregnancy into account,16 it would appear that the
anterior form of PHPV in man develops its main
features in a gestational period of approximately 43
to 66 days of gravidity. Aguirre13 stated that extrapo-
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r
14
0.1 mm
Fig. 14. D44; section of the optic nerve region. A conically
shaped clump of glial tissue (G) is located on the nerve head. (N
= optic nerve; HA = hyaloid artery; R = retina; V = vitreous).
PAS; X10.
lation of ocular developmental events from man to
dog could easily be erroneous, because in man the
embryological development of the eye occurs relatively earlier in gestation than in dog. Therefore, the
above-mentioned gestational period has been placed
in comparable time scales for five mammal species,
including man and dog.16 Thus, the risk of drawing
erroneous conclusions is brought to an acceptable
minimum.
One of the most remarkable changes observed in
the studied fetuses was the overdevelopment of the
hyaloid system and TVL. An increased growth promotion or decreased inhibition of intravitreal angiogenesis by humoral factor(s)19 20 is probable. For this
reason further studies on the ontogenesis of PHTVL/
PHPV in the Dobermann pinscher dog will involve
the regulation of intravitreal angiogenesis, as well as
ultrastructural aspects of the entity.
Key words: PHTVL/PHPV, eye, vitreous, morphogenesis, dog
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INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / July 1988
Acknowledgments
The authors wish to thank the Professors J. A. Oosterhuis
(Leiden) and W. A. Manschot (Rotterdam) for their helpful
criticism.
References
1. Reese AB: Persistent hyperplastic primary vitreous. Am J Ophthalmol 40:317, 1955.
2. Manschot WA: Persistent hyperplastic primary vitreous. AMA
Arch Ophthalmol 59:188, 1958.
3. Pruett RC and Schepens CL: Posterior hyperplastic primary
vitreous. Am J Ophthalmol 69:535, 1970.
4. Haddad R, Font RL, and Reeser F: Persistent hyperplastic
primary vitreous: A clinicopathologic study of 62 cases and
review of the literature. Surv Ophthalmol 23:123, 1978.
5. Grimes TD and Mullaney J: Persistent hyperplastic primary
vitreous in a greyhound. Vet Rec 85:607, 1969.
6. Stades FC: Persistent hyperplastic tunica vasculosa lentis and
persistent hyperplastic primary vitreous in 90 closely related
Dobermann pinschers: Clinical aspects. Journal of the American Animal Hospital Association 16:739, 1980.
7. Curtis R, Barnett KC, and Leon A: Persistent hyperplastic
primary vitreous in the Staffordshire bull terrier. Vet Rec
115:385, 1984.
8. Leon A, Curtis R, and Barnett KC: Hereditary persistent hyperplastic primary vitreous in the Staffordshire bull terrier.
Journal of the American Animal Hospital Association 22:765,
1986.
9. Stades FC: Persistent hyperplastic tunica vasculosa lentis and
persistent hyperplastic primary vitreous in Dobermann
pinschers: Techniques and results of surgery. Journal of the
American Animal Hospital Association 19:393, 1983.
10. Van der Linde-Sipman JS, Stades FC, and De Wolff-Rouendaal D: Persistent hyperplastic tunica vasculosa lentis and persistent hyperplastic primary vitreous in the Doberman
pinscher: Pathologigal aspects. Journal of the American Animal Hospital Association 19:791. 1983.
Downloaded From: http://iovs.arvojournals.org/ on 05/10/2017
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11. Stades FC: Persistent hyperplastic tunica vasculosa lentis and
persistent hyperplastic primary vitreous in Dobermann
pinschers: Genetic aspects. Journal of the American Animal
Hospital Association 19:957, 1983.
12. Duke-Elder S: System of Opthalmology: Vol. 3, Normal and
Abnormal Development. London, Henry Kimpton, 1963.
13. Aguirre GD, Rubin LF, and Bistner SI: Development of the
canine eye. Am J Vet Res 33:2399, 1972.
14. Gloor BP: Zur Entwicklung des Glaskoerpers und der Zonula:
I. Ueberblick und chronologischer Ablauf der Glaskoerperund Zonulaentwicklung beim Kaninchen. Graefes Arch Klin
Exp Ophthalmol 186:299, 1973.
15. Gloor BP: Zur Entwicklung des Glaskoerpers und der Zonula:
II. Glaskoerperzellen waehrend Entwicklung und Rueckbildung der Vasa hyaloidea und der Tunica vasculosa lentis.
Graetes Arch KJin Exp Ophthalmol 186:311, 1973.
16. Boeve MH, Van der Linde-Sipman JS, and Stades FC: Early
morphogenesis of the canine lens, lens capsule, hyaloid system
and vitreous body. Anat Rec 220:435, 1988.
17. Boeve MH, Van der Linde-Sipman JS, and Stades FC: Morphogenesis of persistent hyperplastic tunica vasculosa lentis/
persistent hyperplastic primary vitreous (PHTVL/PHPV) in
the dog. IRCS Med Sci 13:255, 1985.
18. Stades FC: Persistent hyperplastic tunica vasculosa lentis and
persistent hyperplastic primary vitreous in the Dobermann
pinscher. Thesis, Utrecht, 1983.
19. Brem S, Preis I, Langer R, Brem H, Folkman J, and Patz A:
Inhibition of neovascularization by an extract derived from
vitreous. Am J Ophthalmol 84:323, 1977.
20. Lutty GA, Mello RJ, Chandler C, Fait C, Bennett A, and Patz
A: Regulation of cell growth by vitreous humour. J Cell Sci
76:53, 1985.
21. Gloor BP: Zur Entwicklung des Glaskoerpers und der Zonula:
III. Herkunft, Lebenszeit und Ersatz der Glaskoerperzellen
beim Kaninchen. Graefes Arch Klin Exp Ophthalmol 187:21,
1973.
22. Balazs EA: Fine structure of the developing vitreous. In International Opthalmology Clinics, Ocular Fine Structure for the
Clinician, Vol. 15, Zinn K, editor. Boston, Little Brown, 1975