Glycogen Accumulation in Retinal Neurons and Glial Cells of Streptozotocin-diabetic Rats: Quantitative Electron Microscopy

Abstract

The concentration of glycogen |3-particles was measured in the inner retinal layers of normal and streptozotocin-diabetic rats with quantitative electron microscopic technics. Diabetes was uncontrolled and of short duration (thirty days). Blood glucose levels in the normal and diabetic animals were 76 ± 8 S.E. and 340 ± 25 S.E. mg./lOO ml. Diabetes caused glycogen accumulation in the amacrine, bipolar, ganglionic, Miiller and capillary mural cells. Quantitative estimates showed significant increases (p < 0.001) in the glycogen concentrations of cells in the nerve fiber layer (NFL), inner plexiform layer (IPL) and inner nuclear layer (INL) of the diabetic retinas.The glycogen concentrations increased from 6.4 ± 0.41 )3-particles per square micron in the normal to 10.5 ± 0.85 in the diabetic Miiller endfeet (NFL); from 12.9 ± 1.5 to 38.6 ± 5.0 in the Miiller processes (IPL); from 0.81 ± 0.13 to 3.37 ± 0.49 in the neural processes (IPL); from 2.7 ± 0.66 to 17.3 ± 2.4 in the amacrine cell bodies (INL). Diabetic glycogen accumulation occurred at a greater rate in the neurons than in the Miiller cells. The amacrine neurons were the most severely affected and contained massive glycogen deposits in their cytoplasm.The glycogen concentration in the neurons was less than that of the Muller cells. However, the Muller cells represent only 'MO per cent of the total cytoplasm of the IPL, whereas the neurons occupy ^90 per cent of this layer. From the above data, it is evident that the neurons contain about one third of the total glycogen of the normal IPL. In the diabetic IPL, the total glycogen is approximately evenly distributed between the neural and glial compartments. DIABETES 23: 221-31, March, 1974. Light microscopic histochemical studies have revealed glycogen in the Mullerian glial cells of the normal rat retina and in the retinal glia of other species, including man. 1 On the basis of these observations it was assumed that retinal neurons do not contain glycogen. Independent histochemical inves-

Abnormal Glycogen Storage by Retinal Neurons in Diabetes

“…The presence of glycogen in retinal neurons, at least in modest amounts has been previously observed by electron microscopy in the amacrine cells of the cat 40 and rat, 31 suggesting that neuronal glycogen deposition per se is not pathologic, and supports recent studies from other parts of the CNS. 13 However, it is likely that the level of glycogen occupancy described above in the perinuclear cytoplasm of the amacrine cells in diabetic rats would eventually disrupt the normal synthetic functions of the endoplasmic reticulum-Golgi complex and downstream transport mechanisms.…”

“…Early studies suggested disturbance of retinal glycogen metabolism during diabetes, [28][29][30] and a small electron microscopic study by Sosula et al 31 showed a disproportionate increase in retinal neurons. However, these observations have been largely overlooked in recent discussion of neuronal dysfunction in diabetic retinopathy, possibly because glycogen is not well retained in current fixation protocols and requires special staining.…”

Vascular transport of insulin to rat cardiac muscle. Central role of the capillary endothelium.

“…Alteration in endothelial function is already considered a characteristic finding in such disease processes as diabetes mellitus, a pathologic condition characterized by abnormalities of both the secretion of insulin and insulin action. In diabetes, retinal capillary beds demonstrate interendothelial leakage of small proteins, increased transcapillary exchange of plasma fluid components, and endothelial cell proliferation, with each of these findings preceding clinically detectable lesions of the retinal microvasculature (23,24). Our data in the present study now suggest that certain capillary endothelia also serve to control the transcapillary movement of insulin, the hormone central to normal glucose homeostasis.…”

Diabetic retinopathy: Some cellular, molecular and therapeutic considerations

“…41 In diabetic animals gross and possibly pathological accumulations of glycogen have been described in retinal amacrine, bipolar and glial cells which reflect sustained supra-normal intraretinal glucose concentrations. 42 Retinal vascular cells also contain scattered glycogen granules, but even in diabetes abnormal deposits are not observed.…”