Summary
The effect of the polycations, protamine sulfate and poly-l-lysine, on the blood-retinal barrier of rat retinal vessels were studied by retrograde perfusion through the aorta or by intracarotid perfusion of the polycation followed by the protein tracer, hemoglobin. Protamine sulfate induced swelling of cytoplasmic organelles and diffuse staining of many endothelial cells by tracer molecules which subsequently entered the subendothelial and perivascular areas. Polylysine caused some diffuse staining but no leakage of tracer through the endothelial cell. Occasionally, tracer was found in the interendothelial junction after protamine perfusion. The results indicate that surface charge is important for maintaining membrane integrity of the endothelial cells and that breakdown of the blood-retinal barrier may be due to the cytotoxic effect of protamine on the endothelial cell.
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Brightman MW, Hori M, Rapoport SI, Reese TS, Westergaard E (1973) Osmotic opening of tight junctions in cerebral endothelium. J Comp Neurol 152:317–326
Essner E, Lin W-L, Gordon S (1986) Surface-associated vesicles in retinal arterioles and venules. Cell Tissue Res 245:431–437
Friedemann V (1943) Blood brain barrier. Physiol. Rev 22:125–145
Gardiner TA, Archer DB (1986) Does unidirectional vescular transport occur in retinal vessels?. Br J Ophthalmol 70:249–254
Goldfischer S, Novikoff AB, Albala A, Biempica L (1970) Hemoglobin uptake by rat hepatocytes and its breakdown within lysosomes. J Cell Biol 44:513–529
Gordon SR, Essner E (1985) Plasma membrane-associated vesicles in retinal capillaries of the rat. Am J Anat 174:161–172
Hardebo JE, Kåhrström J (1985) Endothelial negative surface charge areas and blood-brain barrier function. Acta Physiol Scand 125:495–499
Hart MN, VanDyk LF, Moore SA, Shasby DM, Cancilla PA (1987) Differential opening of the brain endothelial barrier following neutralization of the endothelial luminal anionic charge in vitro. J Neuropathol Exp Neurol 46:141–153
Houthoff HJ, Moretz RC, Rennke HG, Wisniewski HM (1984) The role of molecular charge in the extravasation and clearance of protein tracers in blood-brain barrier impairment and cerebral edema. In: Go KG, Brethmann A (eds) Recent progress in the study and therapy of brain edema. Plenum Press New York pp 67–79
Lin W-L, Essner E (1986) Diffuse cytoplasmic staining of retinal capillary endothelium. J Histochem Cytochem 34: 1325–1330
Lin W-L, Essner E (1987) Luminal vesicles in endothelial cells of retinal and iridial vessels of the rat. Curr Eye Res 6:785–792
Nag S (1984) Cerebral endothelial surface charge in hypertension. Acta Neuropathol (Berl) 63:276–281
Nagy Z, Pappius HM, Mathieson G, Huttner I (1979) Opening of tight junctions in cerebral endothelium. I. Effect of hyperosmolar mannitol infused through the internal carotid artery. J Comp Neurol 185:569–578
Nagy Z, Peters H, Huttner I (1981) Endothelial surface charge: blood-brain barrier opening to horseradish peroxidase induced by the polycation protamine sulfate. Acta Neuropathol (Berl) [Suppl]7:7–9
Nagy Z, Peters H, Huttner I (1983) Charge-related alterations of the cerebral endothelium. Lab Invest 49:662–671
Pino R (1987) Perturbation of the blood-retinal barrier after enzyme perfusion. A cytochemical study. Lab Invest 56:475–480
Pino R, Thouron C (1986) Identification of lectin-receptor monosaccharides on the endothelium of retinal capillaries. Curr Eye Res 5:625–628
Raviola G, Butler JM (1983) Unidirectional vesicular transport mechanism in retinal vessels. Invest Ophthalmol Vis Sci 24:1465–1474
Raviola G, Butler JM (1985) Morphological evidence for the transfer of anionic macromolecules from the interior of the eye to the blood stream. Curr Eye Res 4:503–516
Shakib M, Cunha-Vaz JG (1966) Studies on the permeability of the blood-retinal barrier. IV. Junctional complexes of the retinal vessels and their role in the permeability of the bloodretinal barrier. Exp Eye Res 5:229–234
Shiose Y (1970) Electron microscopic studies on blood-retinal and blood-aqueous barriers. Jpn J Ophthalmol 14:73–87
Strausbaugh LJ (1987) Intracarotid infusions of protamine sulfate disrupt the blood-brain barrier of rabbits. Brain Res 409:221–226
Tso MOM (1980) Pathology of the blood-retinal barrier. In: Cunha-Vaz JG (ed) The blood-retinal barrier. Plenum Press, New York, pp 238–239
Tso MOM (1984) Animal modeling of cystoid macular edema. Surv Ophthalmol [Suppl] 28:512–519
Vorbrodt AW, Lassmann H, Wisniewski HM, Lossinsky AS (1981) Ultracytochemical studies of the blood-meningeal barrier (BMB) in rat spinal cord. Acta Neuropathol (Berl) 55:113–123
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Supported by NIH grant EY04831 and Research to Prevent Blindness, Inc.
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Lin, W.L. Leakage of blood-retinal barrier due to damaging effect of protamine sulfate on the endothelium. Acta Neuropathol 76, 427–431 (1988). https://doi.org/10.1007/BF00686981
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DOI: https://doi.org/10.1007/BF00686981