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Histopathology of the pterygium in population on Croatian Island Rab.Coll
Antropol. 2007 Jan;31 Suppl 1:39-41.
In the 1975-2004
period, 130 cases of pterygium were estimated, 83 males and 47
females, on a small island Rab. Island Rab is located in the north
part of the Adriatic sea, which has very high index of sun radiation.
Pterygium is usually histopathologically defined as a hyperplasia of
conjunctival tissue, elastoid degeneration of subepithelieum and
fragmentation of Bowman's membrane. Our histopathological findings in
73 eyes are following: conjunctiva with neovascularisation, leukocyte
margination and subepithelial basophilic degeneration, proliferation
of conjunctival tissue, acanthosis and squamous metaplasia, and
mucinous elements, focaly present plasma cells, focuses of increased
pigmentisation in basal epithelial layers, tenon capsule with edema,
diffuse neovascularisation and fragmentation of fibrils. These
findings suggest that in severe cases of pterygium histopathologically
exists precancerosis. In conclusion, on the basis of these
histopathological findings, especially in the Tenon capsule, we
suggest that for surgical procedure of pterygium the excision of the
Tenon capsule, extensively under pterygium, is necessary.
Beta-catenin
activation and epithelial-mesenchymal transition in the pathogenesis
of pterygium.
Invest Ophthalmol Vis Sci. 2007;48(4):1511-7.
PURPOSE: To
investigate whether beta-catenin activation and epithelial-mesenchymal
transition (EMT) is involved in the pathogenesis of pterygium.
METHODS: beta-Catenin and E-cadherin expression were examined in
surgically excised tissue and eye bank corneas with intact pterygium.
Snail and Slug, the transcriptional repressors of E-cadherin, and
matrix metalloproteinase (MMP)-7, a down-stream gene regulated by
beta-catenin were also investigated. Epithelial cells undergoing EMT-like
changes were identified by double immunostaining for alpha-smooth
muscle actin (SMA)/vimentin and cytokeratin 14. Transmission electron
microscopy was used to examine the ultrastructure of the pterygial
head. RESULTS: Histopathology showed aberrant fibrotic proliferation
beneath the pterygium epithelium, with epithelial processes extending
into the stroma. Transmission electron microscopy revealed the
dissociation of epithelial cells, which were surrounded by activated
fibroblast-like cells. Characteristic downregulation of E-cadherin and
intranuclear accumulation of beta-catenin and
lymphoid-enhancer-factor-1 in pterygial epithelium were also observed
by immunohistochemistry. Of note, epithelial cells extending into the
stroma were positive for both alpha-SMA/vimentin and cytokeratin 14.
Snail and Slug were immunopositive in the nuclei of pterygial
epithelial cells, but not in normal corneal epithelial cells.
CONCLUSIONS: EMT of basal epithelial cells may play a key role in the
pathogenesis of pterygium.
Expression of
p27(KIP1) and cyclin D1, and cell proliferation in human pterygium.Br
J Ophthalmol. 2007 Jul;91(7):958-61.
BACKGROUND:
The pterygium is a growth onto the cornea of fibrovascular tissue that
is continuous with the conjunctiva, whereas the mechanisms of cell
proliferation in pterygium epithelium are unknown. AIM: To analyse the
histopathology and the expression of cell cycle-related molecules in
pterygium tissues. METHODS: Seven pterygia were surgically removed
using the bare-sclera procedure, and three normal bulbar conjunctivas
were also obtained. Formalin-fixed, paraffin-wax-embedded tissues were
analysed by immunohistochemistry with anti-p27(KIP1), cyclin D1 and
Ki-67 antibodies. RESULTS: Conjunctival epithelium consisted of
several layers of round cells with a few goblet cells. Nuclear
immunoreactivity for p27(KIP1) was noted in many normal epithelial
cells, where cyclin D1 and Ki-67-positive nuclei were intermingled. A
variety of goblet cells were located in the superficial layer of the
pterygium head as well as those of the body epithelia. Several
pterygium epithelial cells were p27(KIP1) positive, whereas nuclear
immunoreactivity for cyclin D1 and Ki-67 was detected in many
epithelial cells. By contrast, immunoreactivity for p27(KIP1), cyclin
D1 and Ki-67 was hardly detected in the pterygium stroma. CONCLUSION:
It is suggested that pterygium growth and development are associated
with the proliferation of epithelium, which is possibly involved in
the expression of cell cycle-related molecules.
Flow
cytometrical analysis of adhesion molecules, T-lymphocyte
subpopulations and inflammatory markers in pterygium.Ophthalmologica.
2006;220(6):372-8.
BACKGROUND/AIM: Pterygium is a relatively frequent ocular surface
disease with an unexplained etiopathogenesis. Our study was carried
out with the aim to identify the presence of inflammatory cells and
mediators such as T-lymphocyte subgroups (CD4 and CD8), intercellular
adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
(VCAM-1) and human leukocyte antigen-DR (HLA-DR) in pterygium tissue.
METHODS: Pterygium tissue, obtained from 24 patients, and normal
conjunctival tissue, from the nasal bulbar conjunctiva obtained from
14 patients operated for ocular perforations or vitrectomy, were
separated into epithelial and stromal components under the microscope
and suspended with phosphate-buffered saline solution to form a
suspension. Cell suspensions were treated with specific antibodies for
ICAM-1, VCAM-1, and HLA-DR and T-lymphocyte subgroups and evaluated
with flow cytometry. The obtained data were compared statistically.
RESULTS: When compared to the control tissue samples, higher rates of
ICAM-1-positive cells, VCAM-1-positive cells and HLA-DR-positive cells
were recorded in pterygium tissue samples. CD4 and CD8 lymphocytes
were also found to be at higher levels when compared to the control
group. There was a statistically significant difference between the
two groups. CONCLUSION: When compared with normal conjunctival tissue,
pterygium tissue had increased levels of T-lymphocyte infiltration and
inflammatory markers demonstrating the possible contribution of
cellular immunity to the pathogenesis.
Rapid
growth of pterygium after photorefractive keratectomy.Optometry.
2006 Oct;77(10):499-502.
BACKGROUND: A
pterygium is a fibrovascular overgrowth of degenerative conjunctiva
over the limbus onto the cornea. The risk factors for pterygium
development include exposure to ultraviolet (UV) light, dust, wind,
heat, dryness, and smoke. As far as we are aware, rapid growth of
pterygium secondary to photorefractive keratectomy (PRK) has not been
reported previously. CASE REPORT: A 49-year-old man presented with
blurring vision in the left eye. The patient had undergone PRK in both
eyes at another surgical center 11 months prior. Examination found a
pterygium extending 3 mm over the corneal midline and covering 60% to
70% of the cornea. Information regarding the extent of the pterygium
in the left eye was limited; however, preoperative drawings showed a
moderate extension of about a 3-mm encroachment into the nasal cornea.
However, the patient stated that the 2 sides "looked similar" before
PRK and that the right side remained "pretty small" after surgery.
CONCLUSION: Several growth factors have been detected in the cornea
during the recovery from PRK surgery. Those growth factors might have
the potential to exacerbate the growth of a pterygium. Further studies
are needed to draw any conclusion regarding the consequence of PRK
surgery on the growth of a pterygium so patients can be better
informed and managed. As eye care providers, we should be aware of the
potential that rapid growth of a pterygium may occur after PRK.
Finding of
conjunctival melanocytic pigmented lesions within pterygium.
Histopathology. 2006 Mar;48(4):387-93.
AIMS:
Conjunctival pigmented lesions have characteristic clinical and
histopathological appearances. Melanocytic pigmented lesions commonly
occur in the conjunctiva, although they have not been previously
reported in pterygium, a common lesion which originates from
conjunctiva. Our aim was to evaluate the possibility of an association
between pterygium and conjunctival melanocytic pigmented lesions.
METHODS AND RESULTS: A total of 80 samples of pterygium excised from
Ecuadorian patients in 2002 were collected. Clinical data were
available regarding age, sex, race and place of residence.
Histological sections were evaluated for the presence of melanocytic
pigmented lesions. Nine cases of conjunctival melanocytic, pigmented
lesions within pterygium were found and were classified according to
the histopathological criteria previously published for pigmented
lesions of the conjunctiva, as naevi and primary acquired melanosis
(PAM) with varying degrees of atypia. Five of the nine cases showed
primary acquired melanosis without atypia, while two cases had atypia;
one case showed features of compound naevus and one lesion was
designated as subepithelial naevus. CONCLUSIONS: Our findings suggest
that conjunctival melanocytic, pigmented lesions occasionally occur in
pterygium. All surgically removed pterygia should undergo careful
histopathological examination.
Distribution
of extracellular matrix proteins in pterygia: an immunohistochemical
study.Graefes
Arch Clin Exp Ophthalmol. 2004
Apr;242(4):332-8.
PURPOSE: This
study was carried out to monitor the expression of extracellular
matrix proteins (ECMs) and metalloproteinases (MMPs) in pterygial
tissue. METHODS: Twenty primary nasal pterygia were studied by
indirect routine immunohistochemistry using 13 different primary
antibodies against 8 ECMs (five collagens, fibronectin, heparan
sulfate, and laminin) fibroblast growth factor (bFGF), von Willebrand
factor (vWF), and 3 MMPs (8, 9, and 13). Secondary antibodies were
fluoresceinated. Intensity of reaction on individual sections was
graded semi-quantitatively. RESULTS: No expression of collagens I, II,
and VII was found. Antibodies against collagen III reacted strongly
positively (+++) with the entire pterygial stroma. Collagen IV
expression was strongly positive in the wall of pterygial blood
vessels, moderately positive (++) in the epithelial basement membrane,
and only weakly positive (+) all over the stroma. Antibodies against
fibronectin reacted moderately positively with stroma, blood vessel
walls and epithelial basement membrane. Heparan sulfate was strongly
expressed in the blood vessel walls and epithelial basement membrane.
Antibodies against bFGF reacted only with pterygial epithelium.
Laminin was strongly expressed in blood vessel wall, moderately (++)
in the epithelial basement membrane and weakly over the entire stroma.
vWF was strongly positive (+++) with pterygial blood vessel walls.
Antibody reactions for MMPs differed. It was strong with pterygial
epithelium (MMPs 8, 9 and 13), strong to moderate with pterygial
stroma (MMPs 8 and 13 versus 9), and absent to weak with pterygial
vascular walls (MMPs 8 and 13 versus 9). CONCLUSIONS: This study
documents the presence of several ECMs but excludes the expression of
others in pterygial tissues. The results especially indicate an active
involvement of MMPs 8, 9 and 13 in the pathogenesis of pterygia.
Expression of
p63 in pterygium and normal conjunctiva.Cornea.
2004 Jan;23(1):67-70.
PURPOSE: The
p63 gene has been identified as a marker of epithelial stem cells.
Because pterygium may arise through an expansion of the proliferative
capacity of the conjunctiva, we sought to document the expression of
p63 in normal conjunctiva and pterygium specimens. METHODS:
Immunostaining for p63 expression was performed on 10 pairs of
pterygium and normal conjunctiva using a monoclonal antibody directed
against human p63. RESULTS: Immunopositive reactions were seen in all
samples. Levels of p63-positive cells were not statistically different
between pterygium and normal conjunctivae (P = 0.7). CONCLUSION: These
results strongly support previous studies that indicate that pterygium
arises as a result of incorrect control of cellular apoptosis rather
than from an increase in proliferative capacity.
The role of
ultraviolet irradiation and heparin-binding epidermal growth
factor-like growth factor in the pathogenesis of pterygium.Am
J Pathol. 2003 Feb;162(2):567-74.
Ultraviolet
(UV) light is one of the major factors implicated in the pathogenesis
of pterygium. The mechanism by which UV light induces this disease
remains elusive. The aim of this study was to evaluate the effects of
UVB irradiation on the expression of growth factors in cultured
pterygium epithelial cells and to demonstrate their distribution
within pterygium. We cultured pterygial epithelial cells from
pterygium explants and these cells were exposed to 20 mJ/cm(2) of UVB.
Total RNA was extracted at 0, 6, and 12 hours after irradiation.
(32)P-labeled cDNA was synthesized and analyzed using microarray
technology to determine the differential expression of 268 growth
factor and cytokine related genes. Semiquantitative reverse
transcriptase-polymerase chain reaction was used to corroborate this
data. Conditioned media derived from cells exposed to UVB irradiation
was analyzed for protein expression by enzyme-linked immunosorbent
assay. Immunohistochemistry was used to evaluate the distribution of
heparin-binding epidermal growth factor-like growth factor (HB-EGF) in
pterygium tissue. Analysis of the hybridization signals revealed that
the genes encoding HB-EGF, fibroblast growth factor 3, and cytotoxic
trail ligand receptor were consistently elevated at 6 and 12 hours
after UVB treatment. HB-EGF mRNA was elevated 6.8-fold at 6 hours
after irradiation and was augmented in culture supernatants after the
same treatment. Furthermore, HB-EGF reactivity was identified in the
epithelium and vasculature of pterygium by immunohistochemistry.
HB-EGF was present in normal limbal epithelium, although it was not
induced in cultured limbal epithelial cells by UV irradiation. HB-EGF
is a potent mitogen, localized in pterygium tissue, and significantly
induced by UVB in pterygium-derived epithelial cells. We postulate
that this growth factor is a major driving force in the development of
pterygia and a means by which UV irradiation causes the pathogenesis
of pterygium.
Immunohistochemical HLA-DR antigen expression with lymphocyte subsets
and proliferative activity in pterygium.
In Vivo.
2002 Sep-Oct;16(5):299-306.
The
immunohistochemical expression of HLA-DR antigen, CD8, CD4, CD68,
S1OO, PCNA and Ki-67 was performed in order to investigate the role of
immune mechanisms in pterygium, in correlation with proliferative
activity. A series of 98 surgically-excised pterygia, 18 pingueculae
and 20 normal conjunctivae, was studied by the avidin-biotin method,
on formalin-fixed, paraffin-embedded tissue. HLA-DR antigen was
abundantly expressed in pterygium epithelial cells, whereas almost no
expression was found in pinguecula and normal conjunctiva. A high
value of Ki-67 and PCNA expression coexisted in the same areas with
HLA-DR antigen expression in pterygium and a statistically significant
positive correlation resulted between them (p = 0.002). Aberrant
infiltration of inflammatory cells (CD4, CD8, CD68, S100) was detected
in pterygium, while lower densities were found in pinguecula and
conjunctiva. The data suggest that immunopathological mechanisms may
contribute in the pathogenesis of pterygium. In addition, the aberrant
HLA-DR antigen expression seems to be correlated with the growth
fraction of the lesion.
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