الفهرس 
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Abstract
Diabetic retinopathy (DR) is one of the most common microvascular complications of
diabetes mellitus. It is the leading cause of acquired blindness in adults. Duration of diabetes,
hyperglycemia, high blood pressure, and increased albumin excretion rate have been identified
as important risk factors for the onset and progression of DR.
The pathology of DR progresses from mild non proliferative abnormalities,
characterized by increased vascular permeability, to moderate and severe non proliferative
diabetic retinopathy, characterized by vascular closure, then proliferative diabetic retinopathy,
characterized by the growth of new blood vessels on the retina and the posterior surface of
the vitreous.
The ischemic conditions resulting from vascular occlusion occurring early in the course of
the disease triggers the release of several angiogenic growth factors which cause vascular
proliferation. Vascular endothelial growth factor (VEGF) is considered to be the most potent
factor for retinal neovascularization.
VEGF-A (commonly referred to as VEGF), is the most important member of the VEGF
family of glycoproteins. It was found to be elevated in the ocular fluids of patients with
proliferative diabetic retinopathy (PDR).
The main functions of VEGF are to promote survival, induce proliferation and enhance
migration and invasion of endothelial cells, which contribute to angiogenesis. It regulates
these functions via interacting with a family of tyrosine kinase receptors.
Several hypotheses are thought to be involved in the endothelial cell survival activity of
VEGF; among them is its ability to induce antiapoptotic proteins like Bcl-2 and A1.
ß-Cell lymphocyte/leukemia-2 (Bcl-2) is a family of apoptosis regulatory gene products
that includes both pro- and anti-apoptotic members. Bcl-2 protein is the founding pro-survival
member of this family and it is involved in the pathogenesis of several malignant and non
malignant conditions that are all characterized by inhibition of apoptosis.
The present work aimed at evaluating the levels of VEGF and Bcl-2 in the serum and
vitreous humor of patients with proliferative diabetic retinopathy.
The study was conducted on forty subjects divided into two groups. The patients group
included twenty five patients (16 females and 9 males) with proliferative diabetic retinopathy,
who were subjected to vitrectomy. Their mean age was 54.44 ± 8.24 years and their mean
duration of diabetes was 16.04 ± 5.7 years. Fifteen apparently healthy individuals were taken
as controls (2 females and 13 males). They were subjected to vitrectomy for various non
proliferative eye diseases. Their mean age was 45.6 ± 10.13 years.
SUMMARY AND CONCLUSION
74
To all studied subjects, detailed history was taken with special stress on age of onset and
duration of diabetes, compliance to treatment, onset of visual complaints and their
progression. Thorough physical examination was done together with full ophthalmologic
evaluation including visual acuity, visual field and slit lamp examination. Fundus examination
was performed by standardized fundus color photography and fluorescein angiography, for the
optic disc, central retinal vessels, the macula and the retina.
Laboratory investigations included measurement of serum levels of fasting glucose, urea,
creatinine, cholesterol (total, HDL-C and LDL-C), triglycerides, alanine and aspartate
aminotransferases (ALT & AST) activities, as well as glycated hemoglobin (Hb A1c)
estimation. VEGF and Bcl-2 were both measured in the serum and vitreous humor of all
studied subjects.
VEGF was found to be significantly increased in the vitreous humor of patients with PDR
when compared to their corresponding control group; with median of 85.06 pg/ml (0 - 1725.78
pg/ml) vs 12.33 pg/ml (0 - 61.61 pg/ml), p= 0.001. On the other hand, serum VEGF was not
significantly higher in the patients than in the control group with median 101.25 pg/ml (0-
666.85 pg/ml) in patients vs 92.51 pg/ml (2.96-438.28 pg/ml) in controls, p> 0.05. No
significant correlation was found between VEGF in serum and vitreous humor of both studied
groups.
Similarly, Bcl-2 was significantly higher in the patients’ vitreous when compared to its
vitreous level in the control group [Median 4.3 ng/ml (0 – 19 ng/ml) in patients vs 0 ng/ml (0 –
10.3 ng/ml) in the control group, with a p= 0.003]. However, no significant difference was
found between its level in the sera of both groups [Median 3.50 ng/ml (0 – 46 ng/ml) in
patients vs 6.70 ng/ml (0 – 32.50 ng/ml) in controls with p > 0.05]. Like VEGF, no significant
correlation could be assessed between vitreous and serum levels of Bcl-2 in either of the
studied groups.
A significant positive correlation was found between serum Bcl-2 and serum VEGF in the
patients group (rho= 0.463, p= 0.020), such correlation was lacking in the control group.
from the present study the following could be concluded:
1. Levels of VEGF and Bcl-2 were significantly higher in the vitreous humor of patients with
PDR when compared to their corresponding levels in the control group suggesting that both
factors are incriminated in the pathogenesis of this disease.
2. Neither VEGF nor Bcl-2 levels in the serum of patients with PDR were significantly higher
than their levels in the controls’ serum. This finding may support the hypothesis that their
increased levels in the vitreous is probably attributed to intraocular synthesis, in response to
retinal hypoxia and ischemia, rather than to serum filtration.
SUMMARY AND CONCLUSION
75
3. A significant positive correlation was found between serum Bcl-2 and serum VEGF in the
proliferative diabetic retinopathy patients. This might suggest that the role of VEGF in
inducing pathological angiogenesis in PDR might be in part due to up regulation of the anti
apoptotic protein Bcl-2 that promotes new vessels survival rendering them resistant to
apoptosis and allowing more endothelial cell proliferation.
RECOMMENDATIONS
1. VEGF together with Bcl-2 will hopefully lead to the discovery of new targets for future
therapy of proliferative diabetic retinopathy as well as other diseases with a neovascular
component.
2. Further studies are needed to assess the relationship between VEGF and Bcl-2 in DR in both
serum and vitreous humor.