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A rat model for sickle cell-mediated vaso-occlusion in retina.
Microvasc Res 1996; 52(3):270-80MR

Abstract

Occlusions of the retinal vasculature are the initiating event in sickle cell retinopathy. In order to understand the mechanism(s) of sickle cell-mediated occlusion, a rat model was developed. Red blood cells (RBCs) from patients homozygous for hemoglobin (Hb) S (SS) or double heterozygous for Hb S and Hb C (SC) were separated on Percoll-Larex continuous density gradients, labeled with fluorescein isothiocyanate (FITC), and delivered via the left ventricle to anesthetized, ventilated rats. Blood gas levels were altered by changing inspired gas and monitored via a femoral arterial catheter. After the RBCs circulated for 5 min, animals were perfused with heparinized saline, the eyes enucleated, and the retinas removed and processed by our ADPase flatmount technique. The retinal vasculature was visualized under dark-field illumination and the FITC-RBCs visualized by fluorescence microscopy. Greater numbers of high-density SS cells (SS4, which consist of dense, dehydrated discocytes and irreversible sickled cells) were retained in the normal rat retinal vasculature than normal-density SS cells (SS2, which have the same density as normal AA cells, but consist of reticulocytes and young cells). Retention of SS4 cells was inversely dependent on the arterial oxygen tension. Most SS4s were retained in capillaries, but a few were observed within precapillary arterioles. The retained RBCs occupied the full lumenal diameter of vessels in most cases. In contrast, very few RBCs from SC donors (normal or high density) were retained in the normal retinal vasculature and retention did not increase significantly with hypoxia. This model demonstrates that high-density SS cells, which include irreversibly sickled cells, are retained in normal rat retinal vessels and that the number retained is oxygen dependent. Furthermore, it appears that trapping, not adhesion, is responsible for retention of RBCs in the normal retinal vasculature because there was preferential retention of SS4 cells, which are known to have lower adherence propensity, and the retained RBCs blocked the full diameter of the vessel. These results also demonstrate that the mechanism of vascular obstruction by SS and SC RBCs is different because low retention of SC cells was observed. The well-known propensity of SC patients to have retinal abnormalities must involve extraerythrocytic factors like increased hematocrit, induction of adhesive molecules and integrins, etc.

Authors+Show Affiliations

Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8954868

Citation

Lutty, G A., et al. "A Rat Model for Sickle Cell-mediated Vaso-occlusion in Retina." Microvascular Research, vol. 52, no. 3, 1996, pp. 270-80.
Lutty GA, Phelan A, McLeod DS, et al. A rat model for sickle cell-mediated vaso-occlusion in retina. Microvasc Res. 1996;52(3):270-80.
Lutty, G. A., Phelan, A., McLeod, D. S., Fabry, M. E., & Nagel, R. L. (1996). A rat model for sickle cell-mediated vaso-occlusion in retina. Microvascular Research, 52(3), pp. 270-80.
Lutty GA, et al. A Rat Model for Sickle Cell-mediated Vaso-occlusion in Retina. Microvasc Res. 1996;52(3):270-80. PubMed PMID: 8954868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A rat model for sickle cell-mediated vaso-occlusion in retina. AU - Lutty,G A, AU - Phelan,A, AU - McLeod,D S, AU - Fabry,M E, AU - Nagel,R L, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - 270 EP - 80 JF - Microvascular research JO - Microvasc. Res. VL - 52 IS - 3 N2 - Occlusions of the retinal vasculature are the initiating event in sickle cell retinopathy. In order to understand the mechanism(s) of sickle cell-mediated occlusion, a rat model was developed. Red blood cells (RBCs) from patients homozygous for hemoglobin (Hb) S (SS) or double heterozygous for Hb S and Hb C (SC) were separated on Percoll-Larex continuous density gradients, labeled with fluorescein isothiocyanate (FITC), and delivered via the left ventricle to anesthetized, ventilated rats. Blood gas levels were altered by changing inspired gas and monitored via a femoral arterial catheter. After the RBCs circulated for 5 min, animals were perfused with heparinized saline, the eyes enucleated, and the retinas removed and processed by our ADPase flatmount technique. The retinal vasculature was visualized under dark-field illumination and the FITC-RBCs visualized by fluorescence microscopy. Greater numbers of high-density SS cells (SS4, which consist of dense, dehydrated discocytes and irreversible sickled cells) were retained in the normal rat retinal vasculature than normal-density SS cells (SS2, which have the same density as normal AA cells, but consist of reticulocytes and young cells). Retention of SS4 cells was inversely dependent on the arterial oxygen tension. Most SS4s were retained in capillaries, but a few were observed within precapillary arterioles. The retained RBCs occupied the full lumenal diameter of vessels in most cases. In contrast, very few RBCs from SC donors (normal or high density) were retained in the normal retinal vasculature and retention did not increase significantly with hypoxia. This model demonstrates that high-density SS cells, which include irreversibly sickled cells, are retained in normal rat retinal vessels and that the number retained is oxygen dependent. Furthermore, it appears that trapping, not adhesion, is responsible for retention of RBCs in the normal retinal vasculature because there was preferential retention of SS4 cells, which are known to have lower adherence propensity, and the retained RBCs blocked the full diameter of the vessel. These results also demonstrate that the mechanism of vascular obstruction by SS and SC RBCs is different because low retention of SC cells was observed. The well-known propensity of SC patients to have retinal abnormalities must involve extraerythrocytic factors like increased hematocrit, induction of adhesive molecules and integrins, etc. SN - 0026-2862 UR - https://www.unboundmedicine.com/medline/citation/8954868/A_rat_model_for_sickle_cell_mediated_vaso_occlusion_in_retina_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0026-2862(96)90064-3 DB - PRIME DP - Unbound Medicine ER -