Adenosine triphosphate-induced photoreceptor death and retinal remodeling in rats.
Bottom Line: Intravitreal administration of adenosine triphosphate (ATP) has recently been found to induce acute photoreceptor death.ATP caused significant loss of visual function within 1 day and loss of 50% of the photoreceptors within 1 week.These extreme changes were also observed in the 2-year-old P23H rhodopsin transgenic rat model of retinitis pigmentosa.
Affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, 3010, Australia.Show MeSH
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Mentions: To investigate the response of inner retinal neurons, retinae were labeled for rod bipolar cells with an antibody against PKCα (Fig. 5). At 3 months post-ATP injection, rod bipolar cell morphology was relatively well maintained in most regions of the retina (Fig. 5B) and, in general, was similar to saline-injected (Fig. 5A) or healthy retinae (Uesugi et al., 1992). In regions where photoreceptors remained, rod bipolar cell nuclei were located in the outer regions of the inner nuclear layer, their dendrites contacted remnant VGLUT1-positive photoreceptor terminals in the outer plexiform layer, and PKCα/VGLUT1-positive terminals were laminated in the inner most region of the inner nuclear layer (Fig. 5B). However, in regions devoid of photoreceptors, rod bipolar cell morphology was more irregular (Fig. 5C). By 6 months after ATP injection, PKCα-positive rod bipolar cells were still present, although they appeared reduced in number, their overall morphology was abnormal, and they laminated irregularly in the inner plexiform layer (Fig. 5E,F). In addition, there were instances of extreme remodeling events with rod bipolar cell dendrites exiting the neural retina and forming VGLUT1-positive contacts in the choroid (Fig. 5F, arrowhead). These instances of neural retina emigration into the choroid were also observed at the light microscopic level (Fig. 5G, arrowheads). Given the unusual nature of this neuronal remodeling, it was of interest to determine whether this change was representative of heritable retinal degenerations. Two-year-old P23H rat retinae were compared (Fig. 5H). The P23H rat had no outer nuclear layer, regions of reduced and remodeled inner nuclear layer, and an abnormal distribution of VGLUT1-positive synapses. In particular, there were distinct regions of PKCα-positive/VGLUT1-positive synapses in the choroid (Fig. 5H, arrow), similar to those seen in the ATP-treated retina at 6 months.
Affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, 3010, Australia.