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A Comparative Study Of Blood-Optic Nerve Barrier Properties In Normal And Diabetic Rats

Posted on:2007-08-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:J P ZhaoFull Text:PDF
GTID:1104360182492999Subject:Ophthalmology
Abstract/Summary:PDF Full Text Request
With the increase of the incidence and the life-span of diabetic patients, the diabetic optic neuropathy has received much attention recently. However, until now the mechanisms of it are not clear. Recent studies have highlighted the association of diabetes mellitus with blood-brain barrier. Taking into account the specialties of the optic nerve, it is necessary to investigate the blood-optic nerve barrier properties. So, the structural and functional characteristics of the blood-optic nerve barrier and the features in diabetes rats are studied separately, the association of the blood-optic nerve barrier with diabetic optic neuropathy by observing the exchange of substances, permeability, barrier properties are explored . The investigation of the blood-optic nerve barrier properties and the mechanisms of the diabetic optic neuropathy have provided some experimental data and theoretical basis for the prevention and treatment of the diabetic optic neuropathy. It is one of the important subjects that should be resolved for senile society in China.The paper is divided into two parts. Firstly, the blood-optic nerve barrier properties are been studied. Secondly, the features in diabetes rats are observed. Part I A comparative study of blood-optic nerve barrierproperties in normal ratsTwenty normal male SD rats' Optic nerve (prelaminar region, lamina cribrosa, retro-laminar region, intraorbital portion, intracanalicular portion, intracranial portion), cerebral cortex, sciatic nerve is removed separately, infrastructure of endothelial cells is observed by electron microscopy. Employing immunohistochemical (IHC) staining technique, the relative distribution is determined for the GLUT-1, OX-26, OX-47, EBA and the extravasated fibrinogen around microvessels. The Alkaline Phosphatase (ALP) and γ-glutamy transpeptidase (γ -GGT) are revealed by using enzyme cytochemistry. Result: The Microvessels in each portion of optic nerve, cerebral cortex and sciatic nerve do share the same tight junctions. By immunocytochemistry, enzyme cytochemistry, microvessels in prelaminar region and sciatic nerve showed noexpression of the OX-26, OX-47, EBA and Y -GGT;but staining positive for GLUT-1 and ALP, fibrinogen is present around microvessels;The microvessels in other parts of optic nerve (lamina, cribrosa, vetro-laminar region, intraorbital portion, intracanalicular portion, intracranial portion and cerebral cortex) have showed positive for GLUT-1, OX-26, OX-47, EBA, ALP and y -GGT. The marked perivascular staining of fibrinogen is not seen. These results have suggested that microvessels in prelaminar region lack the typical BBB characteristics, microvessels in other parts of optic nerve (lamina cribrosa, retro-laminar portion and intracranial) possessed a classical BBB properties.Part II Blood-optic nerve barrier properties in diabetic ratsTwenty diabetic rats induced by the injection of streptozotocin (50mg/kg) into intraperitoneal for 4 months are applied. Ultrastructural change of each portion of optic nerve microvessels (prelaminar region, lamina cribrosa, retro-laminar region, intraorbital portion, intracanalicular portion, intracranial portion) is observed by electron microscopy. Employing immunohistochemical and enzymechemical staining method, the relative distribution is determined for BBB markers and extravasated fibrinogen which serve as endogenous tracers of microvessels permeability. The aims are to exploit the effect of diabetes on the structural and functional features of the blood-optic nerve barrier. The results show that the loss of endothelial tight junctions is seen in each portion of optic nerve microvessels in diabetic rats. By immunohistochemical and enzyme cytochemical staining process, the expression of BBB markers become weaker than normal group in each portion of optic nerve in diabetic rats. The number of extravasated fibrinogen is increased significantly compared with normal rats in prelaminar region. Meanwhile endogenous tracers fibrinogen of microvessels permeability is seen around microvessels in other portion of optic nerve (lamina cribrosa, retro-laminar region, intraorbital portion, intracanalicular portion and intracranial portion). The results show that high glucose could influence the blood-optic nerve barrier properties in diabetic rats resulting in structural alterations and permeability increase.
Keywords/Search Tags:Optic nerve, Blood-optic nerve barrier, Diabetes mellitus
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