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Possible Role of Pigment-epithelium-derived Factor in Corneal Angiogenesis
chromosome 17p13,
17
the same chromosome responsible for stimulators and inhibitors of angiogenesis that may contribute to
autosomal retinitis pigmentosa
18
and Leber congenital amaurosis.
19
retinal neovascularisation.
29
PEDF prevented retinal ischaemia-
induced neovascularisation as it appeared from apoptosis of
Pigment-epithelium-derived Factor as a endothelial cells in a murine model,
30
and PEDF expression
Neuroprotective Factor increased in retinal epithelial cells and the retina following laser
Corneal innervation and reinnervation has been shown to be of
major importance in corneal wound healing. In this context, the
ability of PEDF to protect spinal motor neurons using a culture
model based on a specific defect in glutamate transport in
The underlying mechanisms concerning
amyotrophic lateral sclerosis (ALS) was shown.
20
Additionally, PEDF
treatment significantly increases the survival of embryonic chock
the regulation and balance of pigment-
spinal motor neurons in culture in a dose-dependent way,
epithelial-derived factor and other
promoting neurite outgrowth of cultured motor neurons and also
preventing death of axotomised motor neurons
growth factors involved in angiogenesis
in vivo.
21
of the eye are still unclear.
The known neurotoxicity of glutamate is considered to be an
important mechanism in programmed cell death, and is therefore
related to different neurodegenerative disorders. PEDF inhibited
glutamate-induced apoptosis in cerebellar granulae cells.
22,23
This photocoagulation, suggesting PEDF could play a role in inhibiting
has been shown to be mediated by activation of the transcription neovascularisation.
31
PEDF is further upgraded in differentiated but
factor NF-kappa B (NF-κB); however, PEDF did not regulate the not in non-differentiated RPE cells.
32
antiapoptotic genes Bcl-2, Bcl-x and Mn-SOD.
24
The earlier detected
44-mer peptide 78-121 out of 418 suggested cell-surface receptors The clinical importance of PEDF was emphasised by a study in which
binding to retinoblastoma cells
20
was identified as the PEDF region intraocular PEDF levels were found to be low in human eyes with
responsible for its neuroprotective actions.
25
It is not known whether retinal ischaemia, including proliferative diabetic retinopathy (DR),
PEDF has similar morphogenic effects within corneal development compared with controls, suggesting that the loss of antiangiogenic
to those observed in the development of retinal photoreceptors.
26
inhibition is of importance in mediating neovascularisation.
33
In a
prospective case-control study, PEDF concentrations were low in the
Pigment-epithelium-derived Factor vitreous of patients with choroidal neovascularisation (CNV) and age-
Antiangiogenic Actions in the Eye related macular degeneration (AMD) compared with age-matched
As outlined above, there has been significant progress in our control patients.
34
Experimental studies with intravitreal injections in a
understanding of how PEDF may exert its effects. However, the mouse model of oxygen-induced ischaemic retinopathy prevented
underlying mechanisms concerning the regulation and balance of retinal neovascularisation and suppressed VEGF-induced retinal
PEDF and other growth factors involved in angiogenesis of the eye microvascular endothelial cell proliferation.
35
PEDF was found in
are still unclear. different tissues of the rat eye and expressed in areas of CNV
following laser coagulation, suggesting that PEDF may modulate the
The first presented antiangiogenic actions of PEDF in the process of CNV.
36
Lower levels of PEDF and high expression of VEGF
mammalian eye showed that PEDF angiostatin inhibited were found in the vitreous of patients with DR compared with high
neovascularisation in the retina more efficiently than the earlier levels of PEDF and undetectable levels of VEGF in vitreous samples
well-studied antiangiogenic factors and, furthermore, that under from patients with idiopathic macular hole, suggesting that an
inbalance of PEDF and VEGF may be related to angiogenesis in DR,
which in turn can lead to active proliferative DR.
37
PEDF was also seen
in the subretinal fluid of retinal detachment, which indicates a role in
The known neurotoxicity of glutamate
preventing subretinal neovascularisation.
38
The concentration of PEDF
in tissues may be of crucial importance. Low PEDF concentrations in
is considered to be an important
choroids may play a role in the development of choroidal
mechanism in programmed cell death,
neovascularisation, as PEDF levels were significantly lower in aged
choroids with AMD compared with choroids of age-matched control
and is therefore related to different
patients, whereas levels of VEGF were similar in both groups.
39
neurodegenerative disorders.
Vascular angiogenesis is possibly linked to lymphangiogenesis and
should be considered an advanced multistep process defined as
growth of new vessels from pre-existing ones
40
triggered by hypoxia
hypoxia VEGF secretion was high and PEDF expression low.
27
and inflammation. In corneal angiogenesis, the limbal region is the
Intravitreal injection of PEDF protected retinal photoreceptors from site of origin and neovacularisation can be seen at the surface as well
morphological and functional deterioration in light-exposed rats.
28
as in the stromal layers, depending on the underlying cause.
41
An
In another model with ischaemic-induced retinopathy in rats, VEGF imbalance between proangiogenic and antiangiogenic molecules
levels were found to increase to a greater extent than PEDF levels, seems to be of great importance,
42
as are other factors, including
with a VEGF–PEDF ratio correlating to the observed retinal matrix metalloproteinases. Among the current experimental study
neovascularisation, suggesting an impaired balance between designs, the corneal pocket assay is a widely used method in
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