الفهرس 
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Abstract
Diabetes mellitus is a major public health problem, and the prevalence of T2DM is worldwide. DM is associated with a range of eye diseases, many of which are sight threatening. Retinopathy, the most serious ocular complication. Although prevention of DR through risk factor reduction (controlling hyperglycaemia, hypertension and hyperlipidaemia) will decrease the incidence and impact of this complication, DR remains the leading cause of severe visual impairment (legal blindness) among working age adults. ET-1 is the most abundantly and widely expressed member of the endothelin family of proteins (ET-1,ET-2, and ET-3). ET-1 is a 21-aa peptide hormone that has a potent vasconstrictor with proliferative, profibrotic, and proinflammatory properties, may contribute to many facets of diabetic vascular disease. The major source of ET-1 are endothelial cells. Synthesis of the biologically active 21-aa ET-1 peptide is a multistep process. Expression of ET-1 is mainly regulated at the transcriptional level, but post-transcriptional mechanisms have also been described. The synthesis and secretion of ET-1 is increased by various growth factors, cytokines and vasoactive factors such as angiotensin II, vasopressin, bradykinin, norepinephrine, and ET-1 itself. Hypoxia and shear stress have also been shown to increase ET-1 release from endothelial cells.
ET-1 expression is suppressed by several factors including atrial natriuretic peptide, nitric oxide, prostacyclin, and heparin. ET-1 mediates its diverse effects via two distinct G protein-coupled receptor (GPCR) subtypes, ETA and ETB. A number of antagonists of ETA and ETB receptors have been described. The endothelin system, consisting of ET-1-3, their receptors ET-A and ET-B, and the two processing enzymes ECE-1 and ECE-2, has been implicated in a variety of physiological and pathophysiological processes including DR. Endothelial dysfunction, defined as an imbalance of endothelium-derived vasoconstrictor and vasodilator substances - which involves changes in ET-1 expression- , is a common denominator in the pathogenesis and progression of both macro and microvascular diabetic complications. Ocular tissues, for example, vascular and extravascular sites in the retina are sources of ET-1, and ET-1 contributes to abnormal retinal haaemodynamics in DR. ET-1 is present in the aqueous humour at concentrations several times higher than in plasma, presumably because it is secreted by the ciliary epithelium and not derived from plasma. This study was carried out to assess the importance of mRNA for ET-1 in DR. This study was carried out at Medical Biochemistry and Ophthalmology Departments, Menofia University, Faculty Of Medicine on 50 subjects: 14 type II diabetic patients without DR, 26 type II diabetic patients with DR and 10 age and gender matched healthy individuals served as controls.
The results of this study can be summarized as follows: As regards clinical and biochemical parameters:- There was no significant statistical difference among the three studied groups as regards age and gender distribution and BMI. There was a significant statistical increase as regards the duration of DM and number of patients treated with insulin and a significant decrease in sulfonylurea in group II when compared to group I. While, there was a non significant statistical difference among the three studied groups as regards SBP, DBP, family history of DM and smoking. There was no significant statistical difference in the number of patients treated with metformin on comparing two diabetic groups. There was a significant statistical difference among the three studied groups regarding all biochemical parameters except serum creatinine. There was a significant statistical difference regarding HbA1c, HDLc, TG, TC, A/C ratio while there is no significant statistical difference regarding FBG, LDLc and serum creatinine when group I was compared with group II .There was a significant statistical difference regarding all biochemical parameters except serum creatinine when group I was compared with group III and when group II was compared with group III. There was no significant statistical difference among the two subgroups of group II (PDR and NPDR) regarding all parameters except A/C ratio. As regards relative quantitation (RQ) of ET-1 mRNA: Regarding RQ of ET-1 mRNA, there was a significant statistical difference among the all studied groups.