动物模型 z-bo 2020-08-03 592

　　Dry eye disease, also known as dry cornea and conjunctiva, is one of the most common diseases in ophthalmology. It can cause ocular surface damage or impaired vision and affect the quality of life of patients. At present, in most patients, the cause of dry eye is not clear, but the more serious dry eye is mainly related to autoimmunity. Animal research has always been an important tool for studying its etiology. So far, the model of dry eye disease mainly involves the removal of the lacrimal gland, the removal of the ocular surface innervation, and the regulation of animal sex hormone secretion. it is. Recent research results indicate that immune changes play an important role in the pathogenesis of dry eye. Therefore, the currently established dry eye model is autoimmune, which mainly causes inflammation on the ocular surface or lacrimal gland. This is a model. Below, we mainly introduce the gene knockout mouse model.

　　[Modeling mechanism] Many experimental results show that dry eye disease is an inflammatory autoimmune disease. This is indicated by the infiltration of autoimmune T cells on the ocular surface and the long-term chronic inflammation of tear functional units, leading to loss of corneal barrier function. , Apoptosis of ocular surface epithelial cells, loss of goblet cells and ocular surface squamous metaplasia.

　　MRL/lpr mice were successfully bred in 1978 by Murphy and Ross of Jackson Laboratory in the United States. Several different strains of LG/J, AKR/J, C3H/D and C57BL/6 mice have undergone a series of complex processes. These processes are produced when the hybridization reaches the 12th generation. The transposon is the Fas gene . It is inserted into the introns of mice, causing abnormal expression of Fas transcription, unable to induce apoptosis, making lymphocyte proliferation out of control, and inhibiting T lymphocyte proliferation.

　　[Model Features] When MRL/lpr mice are one month old, they will develop lacrimal gland inflammation, while in MRL/+ mice, they will develop lacrimal gland inflammatory infiltration. Not as serious as the MRL/lpr mouse, but in the mouse. Lacrimal gland inflammation also occurs at 3 months of age. This shows that the lpr mutation will only aggravate the development of dry eye, but not the cause of its formation. It can be concluded that mutations in the lpr gene do not cause lacrimal glands, because the apoptosis of defective lymphocytes in MRL/lpr mice is caused by mutations in the autosomal recessive gene lpr, and in addition to the lacrimal glands, it produces Fas antigen. I can do it. The only factor that changes the microenvironment. Mutations in the lpr gene will not cause serious autoimmune diseases. This is because no lymphocyte mutations were found in the tear glands of male C3H/lpr mice and mice with systemic lymphoproliferative disease (systemic lymphoproliferative disease). These findings seem to support the hypothesis that Fas antigen and Fas antibody are not the main factors of lacrimal gland immune damage. The immunopathological mechanism of this model is unique, mainly the Th2-type hypersensitivity of IL-4 and B7-2 in lacrimal gland tissue.