Basement membrane composition in the normal and diabetic retina

基底膜是细胞粘附、迁移和分化所必需的。它们在组织边界的划定以及血管和神经网络的形成中也起着特殊的作用。糖尿病患者细胞外基质沉积的变化已经确定；然而，在正常和糖尿病视网膜基底膜的分子组成只有很少的描述。此外，基底膜成分的细胞受体库的改变以及这些变化对视网膜细胞的影响尚未得到彻底的研究。我们将使用一组针对主要基底膜蛋白及其受体的抗体来描述正常小鼠和两种糖尿病小鼠模型中视网膜基底膜的组成。将对处于疾病不同阶段的小鼠进行研究。一旦确定了具有改变表达谱的候选蛋白，将对其在患病人眼中的表达模式进行检查。最后，在可能的情况下，将研究携带这些蛋白质零突变的小鼠是否存在任何眼部表型，并将其繁殖到糖尿病模型菌株，并描述病理过程中的任何调节。这将有助于确定基底膜变化在糖尿病视网膜病变发展中的意义。

Basement membranes are required for cellular adhesion, migration and differentiation. They also play a particular role in the delimiting of tissue boundaries and the formation of vascular and neural networks. Changes in the deposition of the extracellular matrix during diabetes mellitus are well established; however the molecular composition of the basement membranes in the normal and diabetic retina is only poorly described. Further, alterations in the repertoire of cellular receptors for basement membrane components and the effects these changes have upon the cells of the retina have not been thoroughly investigated. We will use a panel of antibodies against the main basement membrane proteins and their receptors to describe the composition of the retinal basement membranes in the normal mouse and in two mouse models of diabetes mellitus. Mice at various stages of the disease will be studied. Once candidate proteins with a changed expression profile have been identified they will be examined for their expression pattern in the diseased human eye. Finally, where available, mice carrying null mutations for these proteins will studied for the presence of any ocular phenotype and will be bred to the diabetic model strains and any modulation in the course of the pathology will be described. This will allow determining the significance in the basement membrane changes in the development of diabetic retinopathy.