We studied cerebral lesions in the streptozotocin-diabetic rat, an established model of diabetic retinopathy. A group of diabetic rats all had cerebral lesions, but showed no gross abnormalities of the brain or signs of effects on the central nervous system. Light and electron microscopy of horizontal brain sections stained by a variety of methods showed focal accumulation of collagen fibrils in the basement membranes of arteriole and capillary walls, slight degeneration of random neuronic cells (mainly in the brain stem), and no evidence of perivascular myelin pallor plaques. A marked tendency toward platelet aggregation, which leads to thrombosis, was also seen. There was no difference between results from rats killed 9 and 12 months after streptozotocin injection. The brain lesions bore a close resemblance to those seen in a nutritional encephalopathy known to be induced by a diet deficient in tocopherol and rich in oxidized oil, but differed from that encephalopathy in that the peculiar hypertrophic cerebral astroglia associated with diabetes resembled Alzheimer Type II astroglia. The differences between these cerebral astroglia and the retinal Müller cells may account for the difference in degree between the effects of diabetes on the brain and the retina.
A new animal model of retinoblastoma was developed in newborn inbred CDF rats by intravitreous inoculation of retinal tumor cells (5 X 10(4)/5 microliter) derived from the cultured tumor cell line EXP-5. The retinal tumor from which the cell line originated was induced by a single intravitreous inoculation of human adenovirus serotype 12 (5 microliter of 10(8) TCID 50/0.1 ml) in syngeneic rats. Within 1 month after intravitreous inoculation of EXP-5 cells, a clinically recognizable ocular tumor was obtained in all 39 rats. Ad 12-specific T-antigens were demonstrated in the cultured tumor cells using immunofluorescent techniques. Morphologically these tumor cells closely resembled retinoblastoma, with poorly differentiated intracytoplasmic organelles, solitary cilia with a 9 + 0 tubule pattern, and abnormal nuclear membrane associated with a set of basal bodies. The significance of this highly manipulable retinal tumor cell line is the capability of providing a full-fledged intravitreous tumor in 1-month-old CDF rats, whose actual life span is known to be 42 months. Transplantable retinal tumors described to date are reviewed briefly and compared with the presently reported cell line.
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