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Glenwood G Gum, John Quach, Nicholas Cook, Jenny Walters, Kayla Martinez, Ashley Renteria, Vatsala Naageshwaran, Sandeep Kumar; Retinal Pathognomonic Features and Disease Stages of Diabetic Retinopathy in a Rat Model of Type I Diabetes Mellitus. Invest. Ophthalmol. Vis. Sci. 2020;61(7):754.
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Diabetic retinopathy (DR), a major complication of diabetes mellitus, is one of the leading causes of blindness worldwide. Hyperglycemia-induced oxidative stress and inflammatory breakdown of the blood-retinal barrier (BRB) can cause retinal microvascular leakage and retinal neurodegeneration in DR. Understanding of the underlying pathological mechanisms and stages of this disease in an animal model are essential for developing novel and improved treatments for DR. We have characterized retinal pathognomonic features and stages of DR in a streptozotocin (STZ)-induced model of type I diabetes mellitus in Sprague Dawley rats.
Rats were administered a single IV dose of 45 mg/kg STZ in 50 mM sodium citrate buffer pH 4.5 (N=10) or sodium citrate buffer (N=5) only. Blood glucose (BG) was measured twice daily. Post induction, rats were screened via slit-lamp, fluorescein angiography, and optical coherence tomography (OCT).
Post STZ induction, BG levels ranged from 250 to >500 mg/dl. Rats with BG >300 mg/dL were considered to be type I diabetic (DB). Day 7, inflammatory cells in the vitreous, on the vitreoretinal interface, and more pronounced near the optic disc were observed. Marked increases in the number of these cells were detected with disease progression. Retinal microaneurysms were detected on Day 21 and later progressed to vascular leakage. Day 52, OCT revealed retinal edema near leakage in ganglion cell, inner plexiform, and inner nuclear layers. Degenerative changes in photoreceptors and thickening of the retinal pigment epithelium (RPE) basement membrane were also prominent. Electroretinogram shows reduction in the amplitude of a- and b- waves. DB rats also developed cortical/central lens opacities by Day 52. These features were absent in buffer-injected rats.
This data indicates that at the early stage of diabetes mellitus, hyperglycemia causes infiltration of inflammatory cells in vitreous humor and retina, which induce aneurysms in retinal vessels. Progression of DR gave rise to retinal edema and thickening of the RPE basement membrane due to fluid accumulation resulting from BRB leakage may further compromise the function of RPE cells, e.g. phagocytosis, and showed degenerative changes to the retina. STZ induced DB rats mimic the human DR condition and are useful for studying DR pathogenesis and development of novel treatments for DR.
This is a 2020 ARVO Annual Meeting abstract.
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