Ultrastructural Changes in the Retina during the Process of Paclitaxel-Induced Retinotoxicity Correction using Antioxidant Drug
Journal Title: Український журнал медицини, біології та спорту - Year 2017, Vol 7, Issue 5
Abstract
Paclitaxel is widely used in the antiblastic treatment schemes, although with side effects observed. Last ones can include vision defects, whose pathogenesis is determined by a few factors: the structural changes of the pigmental epithelium; the rods and cones termination, oxidation caused damage, mitochondrial dysfunction. From our point of view, such states’ treatment or correction can be conducted by means of antioxidants. The purpose of the research is to study the ultrastructural changes in the retina during the Paclitaxel-induced retinotoxicity correction using Armadin. Materials and methods. 80 white rats received intraperitoneal injections of Paclitaxel (Actavis, Romania) dosed 2 mg/kg of body weight, 4 times every 24 hours were examined. The total dosage equaled 8 mg/kg. 48 animals were injected with Armadin at the dosage of 10 mg/kg of body weight (the control group of 32 animals received intraperitoneal injections of water). Pieces of retina were taken to be studied using the electronic microscope. Results. One day after the last Armadin injection the rods and cones layer showed the unequal thickness of rods as well as dystrophic and destructive changes in the inner segment of rods; the connecting cilium was often destroyed. We could observe swelling, outer segments deformation, disorganization of the membranous discs of rods and their vacuolization. Between the outer segment discs separate melanosomes and their groups could be defined. In the neuron perikaryons the neuroplasm was swollen, the organelles were hard to recognize, the processes of photoreceptor and bipolar cells were of different sizes, and the components of the spherule became more recognizable. In bipolar neurons the neuroplasm contained mitochondria with shortened cristae; there were vacuoles and enlarged cisternae of the smooth endoplasmic reticulum. In the ganglion neurons the neuroplasm was swollen. In the retina capillaries the endothelial layer was thin. On the 7th and 15th days the pigment cells became active; they contained numerous melanosomes, their apical processes have become shorter than those in the control group. The membranous discs of the rods had outstanding contours, there were no big vacuoles. The neuroplasm volume in the perikaryons of photoreceptor cells increased, the mitochondria have well distinguished membranes and cristae. The plasma membrane of the spherules was also distinct. In the cytoplasm of bipolar neurons all organelles were easily identified. In the endothelial cells’ cytoplasm capillaries micropinocytotic vesicles were concentrated along the luminal plasma membrane. On the 21st and 27th days the basal complex state improved. The invaginations of the basal plasma membrane of pigment cells became deeper, and the processes of the apical membrane became shorter, the melanosomes became less numerous. The vacuoles were rare to see, and the cavities of the discs were enlarged. The neuron nuclei were within the frames of norm. The spherules contained mitochondria and were tightly placed alongside the plasma membrane of the horizontal neurons and created numerous synaptic contacts with them. Between the spherules and the horizontal neurons areas of radial glial cells were located. The ultramicroscopic structure of bipolar and ganglion neurons as well as the structures of inner plexiform and neuron fiber layers have been normalized. Within a 60 day term the main plate of capillaries and pigmental epithelium in the main complex (Bruch’s membrane) were expanded. The invaginations of plasma membrane have been deepened; there were lots of mitochondria with thick and tightly packed cristae. Approaching the apical pole we could observe a lot of melanosomes and long processes. The outer segments of photoreceptor cells had the uneven width and contained vacuoles, the intersegmental spaces have been expanded. The synaptic contacts of neurons were less distinct comparing to the previous period. In the endothelial cells of the retina capillaries the cytoplasm was thinned. The neuron processes were deformed and their membranes were not very distinct. In 90 days the pigment cells contained swollen mitochondria in their cytoplasm; Golgi bodies had enlarged vesicles and tubules, the melanosomes were on different stages of development, autofagic vesicles appeared, too. The outer segments of rods and cones continued being deformed. Melanosomes destroyed the nearby membranous discs. The neuron dendrites were swollen and deformed. The synaptic contacts had ambiguous pre- and postsynaptic membranes. The capillaries were characterized by the uneven thickening of the basal membrane. The endothelial cells on the luminal surface acquired sail-shaped processes. In the next period of the experiment (120 days) the ultramicroscopic structure of retina components continued deforming. Conclusions. It has been found out, that the positive effect of Armadin in Paclitaxel-induced retinopathy manifested itself since the 7th-15th day through the activation of pigment cells, the distinct contours of membranous discs in rods and cones; the increased volume of neuron perikaryons; mitochondria had well-distinctive membranes and cristae; the synaptic contacts between the neurons and their processes in the outer plexiform layer (spherules) were well outlined. In the retina capillaries in the cytoplasm of endothelial cells, along the luminal plasma membrane micropinocytotic vesicles were concentrated. On the 21st-27th day the state of the basal complex, of bipolar and ganglion neurons, of inner plexiform and neuron fiber layers improved. Starting from the 60th day the first signs of Armadin lack appeared. On the 90th-120th day the destabilization of cell membranes kept developing, the mitochondria manifested the inner membrane damages; the radial glial cells became more active.
Authors and Affiliations
N. Dovga
Keywords
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