UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS

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2024-11-23 18:03

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Conference: Bucharest University Faculty of Physics 2016 Meeting


Section: Biophysics; Medical Physics


Title:
A Histopathological and Ultrastructural Assessment of the Retinal Changes Caused by Exposure to Hydroxychloroquine


Authors:
Aida GEAMANU (1), Ancuta Elena BACIU (2), Claudia Gabriela CHILOM (3), Constantin D. GEAMANU (4), Alina POPA-CHERECHEANU (1)


Affiliation:
1) Medical and Pharmacy University "Carol Davila" Bucharest, Romania

2) National Institute of Endocrinology "C. I. Parhon", Bucharest, Romania

3) University of Bucharest, Faculty of Physics, P.O. Box MG-11, Măgurele, Romania

4) Foisor” Traumatology and Orthopedics Clinical Hospital, Bucharest, Romania



E-mail
ancutaelenabaciu@yahoo.com


Keywords:
Hydroxychloroquine sulfate, rat, retinal toxicity hydroxychloroquine, histopathology


Abstract:
Hydroxychloroquine sulfate (HCQ) is a lysosomotropic agent administered in the treatment of systemic lupus erythematosus and rheumatoid arthritis, having toxic effects much lower than in the administration of chloroquine. However, there is a possible toxicity at the retinal level that may be caused by this substance. In this study, we followed the structural changes in the retina of rats caused by a prolonged exposure to HCQ and tried to elucidate some less studied aspects regarding retinal changes both in histopathological and ultrastructural levels. For this study there were available 96 albino Wistar male rats. The animals were distributed in 4 equal groups꞉ the members of three groups were treated with increasing doses of HCQ (50, 100, 200 mg/kg HCQ, injected intraperitoneally, in a single dose) and the control group (n = 24) in which saline was administered in the same way, a volume of 0.4 mL, known as control. Treated groups received HCQ for periods of 1, 2, 3 and 4 months after which they were sacrificed in groups of n = 6. The ocular globes were harvested, dissected, and processed for examination by optical microscopy (left eyeball) and electron microscopy (right eyeball). Structural inspection of the retina was performed both with an optical microscope and with transmission electron microscope, and the analysis of retina morphophotometry was achieved with a dedicated and statistical analysis. Both at structural and ultrastructural levels, it was observed that a high-dose was causing long-lasting and destructive effects on retina, due to the chronic administration of HCQ. In the meantime, it was observed that not the same linear relationship has been found between a lower dose, longer lasting time, and destructive retinal lesions. It is obvious that the morphological attributes of retinotoxicity of HCQ is due to the accumulation of HCQ in lysosomes that are found in the ganglion cells and, apparently, in the lower cell layer (inner nuclear and photoreceptor cells) most evident in the group receiving intraperitoneally high dose (100 mg/kg) for a longer period. This study was able to capture the histopathological and ultrastructural changes induced by the chronic administration of HCQ, dose management, and different time periods as compared to the control group.