Limits...
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.

Show MeSH

Related in: MedlinePlus

Cone and rod photoreceptors degenerate following ATP treatment. Sections of retinae from saline- and ATP-treated eyes were labeled for cone photoreceptors (PNA, green), photoreceptor and bipolar cell terminals (VGLUT1, red), and cell nuclei (DAPI, blue) at 3 months (A: saline; B,C: ATP) and 6 months (D: saline; E,F: ATP) post-injection. For each time point, two example regions of ATP-treated retinae are presented. Arrowhead in B indicates an abnormal clump of VGLUT1-positive photoreceptor terminals displaced in the ONL. Asterisks in E indicate RPE cell migration and/or vacuole structures in the retina. 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

License
getmorefigures.php?uid=PMC4265795&req=5

fig04: Cone and rod photoreceptors degenerate following ATP treatment. Sections of retinae from saline- and ATP-treated eyes were labeled for cone photoreceptors (PNA, green), photoreceptor and bipolar cell terminals (VGLUT1, red), and cell nuclei (DAPI, blue) at 3 months (A: saline; B,C: ATP) and 6 months (D: saline; E,F: ATP) post-injection. For each time point, two example regions of ATP-treated retinae are presented. Arrowhead in B indicates an abnormal clump of VGLUT1-positive photoreceptor terminals displaced in the ONL. Asterisks in E indicate RPE cell migration and/or vacuole structures in the retina. 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 further the time course of changes following ATP treatment, various retinal cell markers were used to probe the neurodegenerative process. Retinae from saline- and ATP-treated eyes were labeled for cone photoreceptors (PNA, green), photoreceptor and bipolar cell terminals (VGLUT1, red), and cell nuclei (DAPI, blue) at 3 months (Fig. 4A–C) and 6 months (Fig. 4D-E) post-injection. In the saline-treated eyes, PNA-labeled cone photoreceptor inner/outer segments and terminals were apparent across the outer retina and outer plexiform layers at 3 months (Fig. 4A) and 6 months (Fig. 4D), respectively. Cone terminals were found to colocalize with VGLUT1-labeled synapses in the outer plexiform layer in a manner consistent with healthy retinal tissue (Sherry et al., 2003). In ATP-treated eyes, although there were still regions of photoreceptor nuclei at 3 months (Fig. 4B), PNA-labeled cone inner/outer segments were absent, and cone photoreceptor terminals were displaced or absent from the outer plexiform layer. In addition, VGLUT1-labeled photoreceptor terminals were displaced into the outer nuclear layer (Fig. 4B, arrowhead). In other regions where photoreceptor nuclei were absent, a few, sparse VGLUT1-positive photoreceptor terminals remained (Fig. 4C). By 6 months after ATP administration, evidence of PNA-labeled cones and VGLUT1-positive photoreceptor terminals was negligible (Fig. 4E,F). Also, in some regions, the inner retina had begun to remodel significantly, with large holes representing pigmented cells from the RPE and/or fluid-filled vacuoles located in the inner retina (Fig. 4E, asterisk), as has been described previously (Marc and Jones, 2003), and loss of VGLUT1-positive bipolar cell terminals in the inner plexiform layer (Fig. 4F).


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)

Cone and rod photoreceptors degenerate following ATP treatment. Sections of retinae from saline- and ATP-treated eyes were labeled for cone photoreceptors (PNA, green), photoreceptor and bipolar cell terminals (VGLUT1, red), and cell nuclei (DAPI, blue) at 3 months (A: saline; B,C: ATP) and 6 months (D: saline; E,F: ATP) post-injection. For each time point, two example regions of ATP-treated retinae are presented. Arrowhead in B indicates an abnormal clump of VGLUT1-positive photoreceptor terminals displaced in the ONL. Asterisks in E indicate RPE cell migration and/or vacuole structures in the retina. 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

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

fig04: Cone and rod photoreceptors degenerate following ATP treatment. Sections of retinae from saline- and ATP-treated eyes were labeled for cone photoreceptors (PNA, green), photoreceptor and bipolar cell terminals (VGLUT1, red), and cell nuclei (DAPI, blue) at 3 months (A: saline; B,C: ATP) and 6 months (D: saline; E,F: ATP) post-injection. For each time point, two example regions of ATP-treated retinae are presented. Arrowhead in B indicates an abnormal clump of VGLUT1-positive photoreceptor terminals displaced in the ONL. Asterisks in E indicate RPE cell migration and/or vacuole structures in the retina. 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 further the time course of changes following ATP treatment, various retinal cell markers were used to probe the neurodegenerative process. Retinae from saline- and ATP-treated eyes were labeled for cone photoreceptors (PNA, green), photoreceptor and bipolar cell terminals (VGLUT1, red), and cell nuclei (DAPI, blue) at 3 months (Fig. 4A–C) and 6 months (Fig. 4D-E) post-injection. In the saline-treated eyes, PNA-labeled cone photoreceptor inner/outer segments and terminals were apparent across the outer retina and outer plexiform layers at 3 months (Fig. 4A) and 6 months (Fig. 4D), respectively. Cone terminals were found to colocalize with VGLUT1-labeled synapses in the outer plexiform layer in a manner consistent with healthy retinal tissue (Sherry et al., 2003). In ATP-treated eyes, although there were still regions of photoreceptor nuclei at 3 months (Fig. 4B), PNA-labeled cone inner/outer segments were absent, and cone photoreceptor terminals were displaced or absent from the outer plexiform layer. In addition, VGLUT1-labeled photoreceptor terminals were displaced into the outer nuclear layer (Fig. 4B, arrowhead). In other regions where photoreceptor nuclei were absent, a few, sparse VGLUT1-positive photoreceptor terminals remained (Fig. 4C). By 6 months after ATP administration, evidence of PNA-labeled cones and VGLUT1-positive photoreceptor terminals was negligible (Fig. 4E,F). Also, in some regions, the inner retina had begun to remodel significantly, with large holes representing pigmented cells from the RPE and/or fluid-filled vacuoles located in the inner retina (Fig. 4E, asterisk), as has been described previously (Marc and Jones, 2003), and loss of VGLUT1-positive bipolar cell terminals in the inner plexiform layer (Fig. 4F).

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