Pathophysiology Section

Etiology of Diabetic Retinopathy in Humans and Rat Model:

Diabetic retinopathy in humans is mainly a vascular disease, primarily affecting the capillaries. The first ultrastructural and microscopic changes reported are retinal capillary basement membrane thickening and pericyte degeneration, both of which compromise the integrity of the capillary wall. Pericyte degeneration leaves lightly stained compartments in the basement membrane sheath called pericyte "ghosts" (Figure 3A). Electron microscopy shows that these contain degenerated remnants of cytoplasm (Figure 3B), which are eventually replaced by extensions of glial cell cytoplasm.

Figure 3A. Intramural Pericyte Loss in Human Retinal Capillaries: Light micrograph of capillaries from the perimacular region, showing intramural pericyte ghosts (pg) and nuclei of normal endothelial cells (e) and pericytes (p).

Figure 3B. Intramural Pericyte Loss in Human Retinal Capillaries: Electron micrograph of a capillary from a similar region of the companion eye, showing normal appearing red blood cell (rbc), lumen (L), and endothelial cell (e), but abnormally thickened basement membrane material (bm) and degenerated cytoplasmic remnants in all the intramural pericyte compartments (pg). The calibration bars represent 10 mm and 1.0 mm, respectively. (Robison, W.G., Jr., Laver, N.M. and Lou, M.F.: The role of aldose reductase in diabetic retinopathy: prevention and intervention studies. p. 593-640. In Osborne, N.N. and Chader, G.J. (Eds.): Progress in Retinal and Eye Research v. 14, Oxford, Pergamon, 1995).

Similar changes in the retinal capillary walls are also the first lesions to occur in the retinopathy that develops in the galactose-fed rat model of diabetic ocular complications (Figure 4).

Figure 4A. Intramural Pericyte Loss in Rat Retinal Capillaries: Retinal capillaries from rats fed 50% galactose for 6 months beginning at weaning showing, by light microscopy with PAS/hematoxylin stain(A), an intramural pericyte ghost (pg), without a nucleus, as well as endothelial cells (e) and pericytes (p) with normal nuclei; and, by electron microscopy.

Figure 4B. Intramural Pericyte Loss in Rat Retinal Capillaries: A capillary with a normal lumen (L) and endothelial cell lining (e) but abnormally thickened basement membrane material (bm) and degenerated cytoplasmic remnants representing pericyte ghost (pg) cytoplasm in all the intramural pericyte compartments. The calibration bars represent 10 mm and 1.0 mm, respectively. (Robison, W.G., Jr., Laver, N.M. and Lou, M.F.: The role of aldose reductase in diabetic retinopathy: prevention and intervention studies. p. 593-640. In Osborne, N.N. and Chader, G.J. (Eds.): Progress in Retinal and Eye Research v. 14, Oxford, Pergamon, 1995).