INVESTIGADORES
TORBIDONI Ana vanesa
congresos y reuniones científicas
Título:
Endothelin and Endothelin Receptors in Retinal Neuroinflammation.
Autor/es:
M IRIBARNE, V TORBIDONI, AM SUBURO.
Lugar:
Florida, United States.
Reunión:
Congreso; Association for Research in Vision and Ophthalmology Annual meeting; 2006
Institución organizadora:
Association for Research in Vision and Ophthalmology
Resumen:
Purpose: Damage of central nervous system induced by sepsis is a consequence of endothelial dysfunction leading to neural damage. Endothelin1 (ET1), a small peptide released during shock and sepsis, has been involved in the control of bloodbrain barrier. Therefore, we investigated the role of ET1 and its receptors, ETA and ETB, in retinal neuroinflammatory responses induced by endotoxin injection.
Methods: Endotoxemia was induced by ip injection of LPS (5 mg/kg) to male BALBc mice. Samples were obtained after 24 h of LPS injection. Endothelinergic receptors were blocked with 2 doses of tezosentan (T, 10 mg/kg, sc), 1 hour before LPS and 1 hour before euthanasia, respectively. Since saline solution (S) replaced LPS and/or T in control animals, 4 experimental groups: SS, ST, LPSS and LPST were compared. Vascular permeability was examined with Evans Blue. Glial fibrillary acidic protein (GFAP), ET1, ETA and ETB were examined immunohistochemically in retinal wholemounts and cryosections. GFAP was also evaluated in Western blots.
Results: After LPS, retinas exhibited Evans Blue leakage around the optic nerve head, and contained obvious sites of focal dye leakage and cell extravasation along the inner retinal vascular plexus. Astrocytes showed large increases in GFAP and ETB immunoreactivities. LPS also induced a large increase of neuronal ETA immunoreactivity in the outer plexiform layer, amacrine cells and cells of the ganglion cell layer.
Vascular permeability and cell extravasation were significantly reduced in LPST mice, together with ET1 and ETB astrocytic expression. GFAP, however, remained elevated, both in wholemounts and Western blots. ETA immunoreactivity was also reduced.
In ST mice, astrocytes presented a decrease in ET1 immunoreactivity accompanied by a slight increase of ETB immunoreactivity. Neuronal ETA was decreased.
Conclusions: Our observations demonstrate that endotoxemia affects both glial and neuronal cells of the retina and that inhibition of endothelinergic receptors can reduce both glial and neuronal effects. Endothelinergic mechanisms in astrocytes would be primarily involved in the response to sepsis, as supported by the increase of astrocytic ETB and GFAP induced by LPS and the reduction of astrocytic ETB in LPST mice. These observations, together with the large decrease of astrocytic ET1 in ST mice, suggest that perivascular astrocytes might control endothelial permeability by accumulation ET1 and regulation of the extracellular levels of this peptide.