Abstract
• Background: No satisfactory primate model of diabetic retinopathy has been produced. The clinical picture of microangiopathic retinopathy in diabetic hypertensive monkeys has been previously reported. The present study describes the pathologic findings of these animals. • Methods: Eleven eyes of six monkeys (five rhesus, one cynomolgus) were studied. Diabetes mellitus was either spontaneous or induced by streptozocin; mild arterial hypertension was either spontaneous or induced by fludrocortisone acetate. In two monkeys, the horseradish peroxidase tracer technique was employed. Trypsin flat preparations of the nasal retinal vasculature were prepared. The material was studied by light and electron microscopy. • Results: We divided the development of the microangiopathic retinopathy into three stages. In the early stage, background retinopathy was characterized by microvascular abnormalities and capillary dropout. Massive vascular leakage, intraretinal exudates and hemorrhage, cystoid degeneration, and cotton-wool spots were features of an exudative retinopathy in the second stage. In the final stage, chronic ischemic retinopathy was characterized by vascular occlusions and areas of retinal atrophy. • Conclusion: Microangiopathic retinopathy in diabetic monkeys with mild hypertension presented many features of human diabetic and hypertensive retinopathy, except vitreous neovascularization.
Similar content being viewed by others
References
Addison DJ, Garner A, Ashton N (1970) Degeneration of intramural pericytes in diabetic retinopathy. Br Med J 1:264–266
Ashton N (1972) The eye in malignant hypertension. Trans Am Acad Ophthalmol Otolaryngol 76:17–40
Ashton N (1974) Vascular basement membrane changes in diabetic retinopathy. Montgomery Lecture 1973. Br J Ophthalmol 58:344–366
Ashton N (1983) Pathogenesis of diabetic retinopathy. In: Little HL, Jack RL, Patz A, Forsham PH (eds) Diabetic retinopathy. Thieme-Stratton, New York, pp 85–106
Bansal N, Majithia N, Majumdar S, Chakravarti RN (1986) Small vessel disease in vasectomized diabetic monkeys: light microscopic study. Appl Pathol 4:219–224
Barnett KC (1981) Diabetic retinopathy in the dog. Br J Ophthalmol 65:312–314
Bell RH Jr, Hye RJ (1983) Animal models of diabetes mellitus: physiology and pathology. J Surg Res 35:433–460
Bloodworth JMB Jr, Molitor DL (1965) Ultrastructural aspects of human and canine diabetic retinopathy. Invest Ophthalmol Vis Sci 4:1037–1048
Bloodworth JMB Jr, Engerman RL, Anderson PJ (1973) Microangiopathy in the experimentally diabetic animal. Adv Metab Dis 2 [Suppl]: 245–250
Bresnick GH, Engerman R, Davis MD, de Venecia G, Myers FL (1976) Patterns of ischemia in diabetic retinopathy. Trans Am Acad Ophthalmol Otolaryngol 81:OP694-OP709
Bresnick GH, Davis MD, Myers FL, de Venecia G (1977) Clinicopathologic correlations in diabetic retinopathy. II. Clinical and histologic appearances of retinal capillary microaneurysms. Arch Ophthalmol 95:1215–1220
Bresnick GH, Segal P, Mattson D (1983) Fluorescein angiographic and clinicopathologic findings. In: Little HL, Jack RL, Patz A, Forsham PH (eds) Diabetic retinopathy. ThiemeStratton, New York, pp 37–71
Chahal P, Inglesby DV, Sleightholm M, Kohner EM (1985) Blood pressure and the progression of mild background diabetic retinopathy. Hypertension 7 [Suppl II]:72–83
Cogan DG (1963) Development and senescence of the human retinal vasculature. Doyne Memorial Lecture 1963. Trans Ophthalmol Soc UK 83:465–487
Cogan DG, Toussaint D, Kuwabara T (1961) Retinal vascular patterns. IV. Diabetic retinopathy. Arch Ophthalmol 66:366–378
De Venecia G (1980) The eye in accelerated hypertension. III. Accelerated hypertension in patients with diabetic retinopathy. In: Friedman EA, L'Esperance FA (eds) Diabetic renalretinal syndrome. Grune & Stratton, New York, pp 83–101
De Venecia G, Davis M, Engerman R (1976) Clinicopathologic correlations in diabetic retinopathy. I. Histology and fluorescein angiography of microaneurysms. Arch Ophthalmol 94:1766–1773
De Venecia G, Wallow I, Houser D, Wahlstrom M (1980) The eye in accelerated hypertension. I. Elschnig's spots in nonhuman primates. Arch Ophthalmol 98:913–918
Engerman RL (1976) Animal models of diabetic retinopathy. Trans Am Acad Ophthalmol Otolaryngol 81:OP710-OP715
Engerman RL, Bloodworth JMB (1965) Experimental diabetic retinopathy in dogs. Arch Ophthalmol 73:205–210
Engerman RL, Kern TS (1987) Progression of incipient diabetic retinopathy during good glycemic control. Diabetes 36:808–812
Fine BS, Brucker AJ (1981) Macular edema and cystoid macular edema. Am J Ophthalmol 466–481
Garner A, Ashton M, Tripathi R, Kohner EM, Bulpitt CJ, Dollery CT (1975) Pathogenesis of hypertensive retinopathy. An experimental study in the monkey. Br J Ophthalmol 59:3–44
Giacomelli F, Juechter KB, Wiener J (1972) The cellular pathology of experimental hypertension. VI. Alterations in retinal vasculature. Am J Pathol 68:81–96
Hayreh SS, Servais GE, Virdi PS, Marcus ML, Rojas P, Woolson RF (1985) Fundus lesions in malignant hypertension. III. Arterial blood pressure, biochemical, and fundus changes. Ophthalmology 92:45–59
Hayreh SS, Servais GE, Virdi PS (1985) Fundus lesions in malignant hypertension. IV. Focal intraretinal periarteriolar transudates. Ophthalmology 92:60–73
Hayreh SS, Servais GE, Virdi PS (1989) Cotton-wool spots (inner retinal ischemic spots) in malignant arterial hypertension. Ophthalmologica 198:197–215
Howard CF Jr (1982) Nonhuman primates as models for the study of human diabetes mellitus. Diabetes 31 [Suppl 1]:37–42
Jonasson O, Jones CW, Bauman A, John E, Manaligod J, Tso MOM (1985) The pathophysiology of experimental insulin-deficient diabetes in the monkey: implications for pancreatic transplantation. Ann Surg 210:27–39
Jones CW Reynolds WA, Hoganson GE (1980) Streptozotocin diabetes in the monkey. Plasma levels of glucose, insulin, glucagon, and somatostatin, with corresponding morphometric analysis of islet endocrine cells. Diabetes 29:536–546
Jones CW West MS, Hong DT, Jonasson O (1984) Peripheral glomerular basement membrane thickness in the normal and diabetic monkey. Lab Invest 51:193–198
Jones CW, Cunha-Vaz JG, Zeimer RC, Rusin MM, Langenberg PW, Vygantas CM, Tso MOM, Jonasson O (1986) Ocular fluorophotometry in the normal and diabetic monkey. Exp Eye Res 42:467–477
Kador PF, Takahashi Y, Wyman M, Ferris F III (1995) Diabetes-like proliferative retinal changes in galactosefed dogs. Arch Ophthalmol 113:352–354
Kaga N, Tso MOM, Jampol LM, Setogawa T, Rednam KRV (1982) Talc retinopathy in primates. A model of ischemic retinopathy. II. A histopathologic study. Arch Ophthalmol 100:1644–1648
Kaga N, Tso MOM, Jampol LM (1982) Talc retinopathy in primates. A model of ischemic retinopathy. III. An electron microscopic study. Arch Ophthalmol 100:1649–1657
Keyes JEL, Goldblatt H (1938) Experimental hypertension. VIII. Vascular changes in the eyes. Arch Ophthalmol 20:812–828
Kimura T (1965) Studies on fine structure of retinal blood vessels in arteriolar sclerosis of the human retina (report I). Nippon Ganka Gakkai Zasshi 69:1140–1157
Kimura T (1966) Studies on fine structure of retinal blood vessels in arteriolar sclerosis of the human retina (report II). Nippon Ganka Gakkai Zasshi 70:1442–1454
Kishi S, Tso MOM, Hayreh SS (1985) Fundus lesions in malignant hypertension. I. A pathologic study of experimental hypertensive choroidopathy. Arch Ophthalmol 103:1189–1197
Klein R, Klein BE, Moss SE, Davis MD, DeMets DL (1989) Is blood pressure a predictor of the incidence or progression of diabetic retinopathy? Arch Intern Med 149:2427–2432
Leuenberger PM, Beauchemin ML, Babel J (1974) Experimental diabetic retinopathy. Arch Ophtalmol (Paris) 34:289–302
Marshall G, Garg SK, Jackson WE, Holmes DL, Chase HP (1993) Factors influencing the onset and progression of diabetic retinopathy in subjects with insulin-dependent diabetes mellitus. Ophthalmology 100:1133–1139
Mimatsu T (1963) A histological study of the retinal blood vessels in hypertension. Nippon Ganka Gakkai Zasshi 67:1463–1480
Papachristodoulou D, Heath H (1977) Ultrastructural alterations during the development of retinopathy in sucrose-fed and Streptozotocin-diabetic rats. Exp Eye Res 25:371–384
Speiser P, Gittelsohn AM, Patz A (1968) Studies on diabetic retinopathy. III. Influence of diabetes on intramural pericytes. Arch Ophthalmol 80:332–337
Szabo AJ, Stewart AG, Joron GE (1967) Factors associated with increased prevalence of diabetic retinopathy. Can Med Assoc J 97:286–292
Takahashi Y, Wyman M, Ferris R, III, Kador PF (1992) Diabetes-like preproliferative retinal changes in galactose-fed dogs. Arch Ophthalmol 110:1295–1302
Tilton RG, LaRose LS, Kilo C, Williamson JR (1986) Absence of degenerative changes in retinal and uveal capillary pericytes in diabetic rats. Invest Ophthalmol Vis Sci 27:716–721
Tso MOM (1982) Pathology of cystoid macular edema. Ophthalmology 89:902–915
Tso MOM (1984) Animal modeling of cystoid macular edema. Surv Ophthalmol 28 [Suppl]:512–519
Tso MOM, Shih CY, McLean IW (1975) Is there a blood-brain barrier at the optic nerve head? Arch Ophthalmol 93:815–825
Tso MOM, Kurosawa A, Benhamou E, Bauman A, Jeffrey J, Jonasson O (1988) Microangiopathic retinopathy in experimental diabetic monkeys. Trans Am Ophthalmol Soc 86:389–421
Wallow IH, Engerman RL (1977) Permeability and patency of retinal blood vessels in experimental diabetes. Invest Ophthalmol Vis Sci 16:447–461
West KM (1978) Epidemiology of diabetes and its vascular lesions. Elsevier-North Holland, New York, p 425
Williams JM, de Juan E, Machemer R (1988) Ultrastructural characteristics of new vessels in proliferative diabetic retinopathy. Arch Ophthalmol 105:491–499
Williamson JR, Tilton RG, Chang K, Kilo C (1988) Basement membrane abnormalities in diabetes mellitus: relationship to clinical microangiopathy. Diabetes Metab Rev 4:339–370
Yanoff M (1966) Diabetic retinopathy. N Engl J Med 274:1344–1349
Yanoff M, Fine BS (1989) Retina. In: Yanoff M, Fine B (eds) Ocular pathology, 3rd edn. JB Lippincott, Philadelphia, pp 377–465
Yoshimoto H, Murata M (1977) Permeability of retinal blood vessels in spontaneously hypertensive rats. Jpn J Ophthalmol 21:143–156
Yoshimoto H, Takahashi S (1977) Retinal arterioles in the spontaneously hypertensive and other experimental hypertensive rats. Jpn J Ophthalmol 21:157–175
Yoshimoto H, Matsuyama S (1987) A histopathological study of late-phase severe retinochoroidopathy in experimental renovascular hypertensive rats. Nippon Ganka Gakkai Zasshi 91:756–770
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Büchi, E.R., Kurosawa, A. & Tso, M.O.M. Retinopathy in diabetic hypertensive monkeys: a pathologic study. Graefe's Arch Clin Exp Ophthalmol 234, 388–398 (1996). https://doi.org/10.1007/BF00190716
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00190716