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Adenosine triphosphate-induced photoreceptor death and retinal remodeling in rats.

Vessey KA, Greferath U, Aplin FP, Jobling AI, Phipps JA, Ho T, De Iongh RU, Fletcher EL - J. Comp. Neurol. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, 3010, Australia.

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Rod bipolar cell morphology following ATP-induced photoreceptor degeneration and in P23H rat retinae. Sections of retinae from saline- and ATP-treated rat eyes and a 2-year-old P23H rat retina for comparison were labeled for rod bipolar cells (PKCα, green), photoreceptor and bipolar cell terminals (VGLUT1, red), and cell nuclei (DAPI, blue). A–C: ATP-treated rat retinae at 3 months (A: saline; B,C: ATP). D–F: ATP-treated rat retinae at six months (D: saline; E,F: ATP). For each time point for ATP-treated retinae, two example regions are presented. G: Light microscopic image of ATP-treated rat retina at 6 months. H: Two-year-old P23H rat retina. Arrowheads in F,H indicate extreme remodeling event of VGLUT1/PKCα-positive synapses displaced into the choroid in 6 month ATP retina (F) and 2-year-old P23H rat retina (H). ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer. Scale bars = 20 μm.
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fig05: Rod bipolar cell morphology following ATP-induced photoreceptor degeneration and in P23H rat retinae. Sections of retinae from saline- and ATP-treated rat eyes and a 2-year-old P23H rat retina for comparison were labeled for rod bipolar cells (PKCα, green), photoreceptor and bipolar cell terminals (VGLUT1, red), and cell nuclei (DAPI, blue). A–C: ATP-treated rat retinae at 3 months (A: saline; B,C: ATP). D–F: ATP-treated rat retinae at six months (D: saline; E,F: ATP). For each time point for ATP-treated retinae, two example regions are presented. G: Light microscopic image of ATP-treated rat retina at 6 months. H: Two-year-old P23H rat retina. Arrowheads in F,H indicate extreme remodeling event of VGLUT1/PKCα-positive synapses displaced into the choroid in 6 month ATP retina (F) and 2-year-old P23H rat retina (H). ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer. Scale bars = 20 μm.

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.


Adenosine triphosphate-induced photoreceptor death and retinal remodeling in rats.

Vessey KA, Greferath U, Aplin FP, Jobling AI, Phipps JA, Ho T, De Iongh RU, Fletcher EL - J. Comp. Neurol. (2014)

Rod bipolar cell morphology following ATP-induced photoreceptor degeneration and in P23H rat retinae. Sections of retinae from saline- and ATP-treated rat eyes and a 2-year-old P23H rat retina for comparison were labeled for rod bipolar cells (PKCα, green), photoreceptor and bipolar cell terminals (VGLUT1, red), and cell nuclei (DAPI, blue). A–C: ATP-treated rat retinae at 3 months (A: saline; B,C: ATP). D–F: ATP-treated rat retinae at six months (D: saline; E,F: ATP). For each time point for ATP-treated retinae, two example regions are presented. G: Light microscopic image of ATP-treated rat retina at 6 months. H: Two-year-old P23H rat retina. Arrowheads in F,H indicate extreme remodeling event of VGLUT1/PKCα-positive synapses displaced into the choroid in 6 month ATP retina (F) and 2-year-old P23H rat retina (H). ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer. Scale bars = 20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4265795&req=5

fig05: Rod bipolar cell morphology following ATP-induced photoreceptor degeneration and in P23H rat retinae. Sections of retinae from saline- and ATP-treated rat eyes and a 2-year-old P23H rat retina for comparison were labeled for rod bipolar cells (PKCα, green), photoreceptor and bipolar cell terminals (VGLUT1, red), and cell nuclei (DAPI, blue). A–C: ATP-treated rat retinae at 3 months (A: saline; B,C: ATP). D–F: ATP-treated rat retinae at six months (D: saline; E,F: ATP). For each time point for ATP-treated retinae, two example regions are presented. G: Light microscopic image of ATP-treated rat retina at 6 months. H: Two-year-old P23H rat retina. Arrowheads in F,H indicate extreme remodeling event of VGLUT1/PKCα-positive synapses displaced into the choroid in 6 month ATP retina (F) and 2-year-old P23H rat retina (H). ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer. Scale bars = 20 μm.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, 3010, Australia.

Show MeSH
Related in: MedlinePlus