Summary
Vitreous fluorophotometry was performed on pigmented male rats (Piebald strain) 2 weeks after induction of diabetes by streptozotocin. In vivo fluorophotometry data were compared with measurements obtained by direct extraction of the vitreous 60 min after an intravenous injection of sodium fluorescein. In addition, the rate of fluorescein disappearance from blood plasma, plasma protein binding of fluorescein and the effect of insulin treatment of diabetic animals were investigated. Age-matched nondiabetic animals served as controls. In vivo fluorophotometric measurements showed a good correlation with fluorescein determinations after direct extraction of the vitreous. Vitreous fluorescein concentrations were similar in diabetic and normal rats and were strongly related to the dye plasma levels within each group of animals. In the diabetic rats, however, the elimination of plasma fluorescein was accelerated and the percentage of free fluorescein, as determined by ultrafiltration and equilibrium dialysis, was consistently higher (130–150% of controls). The ratios of vitreous to total or free plasma fluorescein levels were elevated in diabetic rats. Experimental data indicate that plasma concentration of free fluorescein is crucial for vitreous dye accumulation. Insulin treatment of diabetic rats markedly improved their metabolic state and normalized the plasma fluorescein elimination and the vitreous to plasma fluorescein concentration ratios. It is concluded that vitreous fluorophotometry can be adequately applied to pigmented rats, provided that plasma fluorescein elimination rate and protein binding are considered in the interpretation of the results, since both influence the vitreous fluorescein accumulation and both may be altered by disease and drug treatment.
Article PDF
Similar content being viewed by others
References
Cunha-Vaz J, Abren JF, Campos AJ, Figo GM (1975) Early breakdown of the blood-retinal barrier in diabetes. Brit J Ophthalmol 59: 649–656
Waltman SR, Krupin T, Kilo C, Becker B (1979) Vitreous fluorophotometry in adult-onset diabetes mellitus. Am J Ophthalmol 88: 342–345
Krupin T, Waltman SR, Oestrich C, Santiago J, Ratzan S, Kilo C, Becker B (1978) Vitreous fluorophotometry in juvenile-onset diabetes mellitus. Arch Ophthalmol 96: 812–814
White NH, Waltman SR, Krupin T, Santiago JU (1982) Reversal of abnormalities in ocular fluorophotometry in insulin-dependent diabetes after five to nine months of improved metabolic control. Diabetes 21: 80–85
Prager TC, Chu HH, Garcia CA, Anderson RE, Field JB, Orzeck EA, Comstock JP (1983) The use of vitreous fluorophotometry to distinguish between diabetics with and without observable retinopathy: effect of vitreous abnormalities on the measurement. Invest Ophthalmol Vis Sci 24: 57–65
Kjaergaard JJ, Ohrt V (1983) Ocular fluorophotometry in insulintreated diabetic patients with and without retinopathy. Int J Microcirc Clin Exp 2: 207–213
Waltman SR, Krupin T, Hanish S, Oestrich C, Becker B (1978) Alteration of the blood retinal barrier in experimental diabetes mellitus. Arch Ophthalmol 96: 878–879
Tso MO, Cunha-Vaz JG, Shih CY, Jones CW (1980) Clinicopathologic study of blood-retinal barrier in experimental diabetes mellitus. Arch Ophthalmol 98: 2032–2040
Kernell A, Arngvist H (1983) Effect of insulin treatment on the blood retinal barrier in rats with streptozotocin induced diabetes. Arch Ophthalmol 101: 968–970
Krupin T, Waltman SR, Sharp DW, Oestrich C, Feldman SD, Becker B, Ballinger WF, Lacy PE (1979) Ocular fluorophotometry in streptozotocin diabetes mellitus in the rat: Effect of pancreatic islet isografts. Invest Ophthalmol Vis Sci 18: 1185–1190
Klein R, Wallow IH, Ernest JT (1980) Fluorophotometry. III. Streptozotocin-treated rats and rats with pancreatectomy. Arch Ophthalmol 98: 2235–2237
Smith SS, Frank S, Ashburn JR, Pilkerton AR, Recant L (1982) Vitreous fluorophotometry in three models of experimental diabetes mellitus. Retina 2: 121–125
Klein R, Ernest JT, Engerman RL (1980) Fluorophotometry: I. Technique. Arch Ophthalmol 98: 2231–2232
Prager TC, Wilson DJ, Avery GD, Merit JH, Garcia CA, Hoper G, Andeson RE (1981) Vitreous fluorophotometry: identification of sources of variability. Invest Ophthalmol Vis Sci 21: 854–864
Kjaergaard JJ, Dideriksen K, Mourits-Andersen T (1983) Some aspects of the pharmacokinetics of fluorescein in normal and diabetic subjects. Int J Microcirc Clin Exp 2: 191–197
Kjaergaard JJ (1983) Ocular fluorophotometry in normal subjects. Int J Microcirc Clin Exp 2: 199–205
Lorch E (1969) Extraction of free fatty acids from plasma or serum in a continuous flow system. Anal Biochem 28: 307–312
Jensen PK, Sandahl Christiansen J, Steven K, Parving HH (1981) Renal function in streptozotocin diabetic rats. Diabetologia 21: 409–414
Jusko WJ, Gretch M (1976) Plasma and tissue protein binding of drugs in pharmacokinetics. Drug Metab Rev 5: 43–140
Webb JM, Fonda M, Broner EA (1962) Metabolism and excretion patterns of fluorescein and some halogenated fluorescein dyes in rats. J Pharmacol Exp Ther 137: 141–147
Araie M, Sawa M, Nagataki S, Mishima S (1980) Aqueous humor dynamics in man as studied by oral fluorescein. Jap J Ophthalmol 24: 346–362
Rockey JH, Weihe L (1982) Binding of fluorescein and carboxyfluorescein by normal and glycosylated human serum proteins. Ophthalmic Res 14: 416–427
Chahal PS, Neal MJ, Kohner EM (1985) Metabolism of fluorescein after intravenous administration. Invest Ophthalmol Vis Sci 26: 764–768
Maepea O, Karlsson C, Alm A (1984) Blood-ocular and bloodbrain barrier function in streptozotocin-induced diabetes in rats. Arch Ophthalmol 102: 1366–1369
Kirber WM, Nichols CU, Grimes PA, Winegrad AI, Laties AM (1980) A permeability defect of the retinal pigment epithelium. Occurrence in early streptozotocin diabetes. Arch Ophthalmol 98: 725–728
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kaufmann, F., Lacoste, C. Vitreous fluorescein accumulation determined by in vivo fluorophotometry and by vitreous extraction in normal and diabetic rats. Diabetologia 29, 175–180 (1986). https://doi.org/10.1007/BF02427089
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02427089