Low-dose multiple injections of streptozotocin to establish an animal model of early diabetic retinopathy

  OBJECTIVE: To inject multiple small doses of streptozotocin (STZ) to make an animal model of early diabetic retinopathy (DR) in rats.

  Method: 75 male SD rats, weighing (180±; 15) g. They were randomly divided into control group (CON group, n=30) and model group (DM group, n=45). In the DM group, 3% STZ was injected intraperitoneally at 30 mg/kg body weight for 5 consecutive days. After forming the model, measure the weight, blood sugar and other indicators every week. Ten animals in each group were randomly euthanized at the 4th, 8th, and 12th week after modeling, and the retinal tissue was subjected to H.E staining, immunohistochemistry, digestion, and transmission electron microscope ultrastructure observation.

  Result: In the second week after the establishment of the model, the animals showed diabetic symptoms of polyphagia, polydipsia, and polyuria. Compared with the control group, the model rats only saw the thinning of the retina at 4 weeks, the proliferation of retinal endothelial cells, the thickening of capillary basement membrane, the finger-like protrusions of endothelial cells and the increase of swallowing vesicles at 8 weeks. At 12 weeks, the capillaries were enlarged, the capillary cells were apoptotic, and the nucleus was pyknotic and deeply stained. The retina becomes thinner and the number of ganglion cells decreases. The mitochondria of the pericytes of the retina swelled, and the cristae fell off and vacuolated. The GFAP-positive cells in the rat retina of the model group were mainly distributed in the ganglion cell layer and the nerve fiber layer, arranged in a continuous strip, and the number of positive cells was significantly reduced.

   Conclusion: The rat DR model induced by multiple injections of STZ in small doses shows similar characteristics of early human retinopathy, and can be used for research on pathogenesis and pharmacodynamics.