Retinal changes in an ATP-induced model of retinal degeneration
In rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-04-01
|
| Series: | Frontiers in Neuroanatomy |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnana.2016.00046/full |
| _version_ | 1828880377238781952 |
|---|---|
| author | Felix Peter Aplin Kirstan Anne Vessey Chi D Luu Robyn H Guymer Robert K Shepherd Erica Lucy Fletcher |
| author_facet | Felix Peter Aplin Kirstan Anne Vessey Chi D Luu Robyn H Guymer Robert K Shepherd Erica Lucy Fletcher |
| author_sort | Felix Peter Aplin |
| collection | DOAJ |
| description | In rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal sighted felines were unilaterally blinded using intravitreal ATP injections and assessed using electroretinography (ERG) and optical coherence tomography (OCT). At 30 hours (n = 3) or 12 weeks (n = 3) post-injection, the animals were euthanized and the eyes enucleated. Retinae were sectioned and labelled using immunohistochemistry for markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal degeneration was observed in the outer retina at both 30 hours and 12 weeks following unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell displacement and aberrant neurite growth were observed in the inner retina at 12 weeks post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Müller cell gliosis was observed throughout the inner and outer retina, in some parts completely enveloping and/or displacing the surviving neural tissue. Our data suggests that the ATP injected feline retina continues to undergo progressive retinal degeneration and exhibits abnormalities consistent with a description of retinal remodeling commonly seen in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration. |
| first_indexed | 2024-12-13T09:46:31Z |
| format | Article |
| id | doaj.art-9334a71c7fe24d74a8a13c630b6abb20 |
| institution | Directory Open Access Journal |
| issn | 1662-5129 |
| language | English |
| last_indexed | 2024-12-13T09:46:31Z |
| publishDate | 2016-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroanatomy |
| spelling | doaj.art-9334a71c7fe24d74a8a13c630b6abb202022-12-21T23:52:01ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292016-04-011010.3389/fnana.2016.00046189705Retinal changes in an ATP-induced model of retinal degenerationFelix Peter Aplin0Kirstan Anne Vessey1Chi D Luu2Robyn H Guymer3Robert K Shepherd4Erica Lucy Fletcher5The University of MelbourneThe University of MelbourneCentre for Eye Research AustraliaCentre for Eye Research AustraliaThe Bionics InstituteThe University of MelbourneIn rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal sighted felines were unilaterally blinded using intravitreal ATP injections and assessed using electroretinography (ERG) and optical coherence tomography (OCT). At 30 hours (n = 3) or 12 weeks (n = 3) post-injection, the animals were euthanized and the eyes enucleated. Retinae were sectioned and labelled using immunohistochemistry for markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal degeneration was observed in the outer retina at both 30 hours and 12 weeks following unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell displacement and aberrant neurite growth were observed in the inner retina at 12 weeks post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Müller cell gliosis was observed throughout the inner and outer retina, in some parts completely enveloping and/or displacing the surviving neural tissue. Our data suggests that the ATP injected feline retina continues to undergo progressive retinal degeneration and exhibits abnormalities consistent with a description of retinal remodeling commonly seen in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration.http://journal.frontiersin.org/Journal/10.3389/fnana.2016.00046/fullAdenosine TriphosphateGliosisPhotoreceptor CellsRetinaRetinal DegenerationRetinitis Pigmentosa |
| spellingShingle | Felix Peter Aplin Kirstan Anne Vessey Chi D Luu Robyn H Guymer Robert K Shepherd Erica Lucy Fletcher Retinal changes in an ATP-induced model of retinal degeneration Frontiers in Neuroanatomy Adenosine Triphosphate Gliosis Photoreceptor Cells Retina Retinal Degeneration Retinitis Pigmentosa |
| title | Retinal changes in an ATP-induced model of retinal degeneration |
| title_full | Retinal changes in an ATP-induced model of retinal degeneration |
| title_fullStr | Retinal changes in an ATP-induced model of retinal degeneration |
| title_full_unstemmed | Retinal changes in an ATP-induced model of retinal degeneration |
| title_short | Retinal changes in an ATP-induced model of retinal degeneration |
| title_sort | retinal changes in an atp induced model of retinal degeneration |
| topic | Adenosine Triphosphate Gliosis Photoreceptor Cells Retina Retinal Degeneration Retinitis Pigmentosa |
| url | http://journal.frontiersin.org/Journal/10.3389/fnana.2016.00046/full |
| work_keys_str_mv | AT felixpeteraplin retinalchangesinanatpinducedmodelofretinaldegeneration AT kirstanannevessey retinalchangesinanatpinducedmodelofretinaldegeneration AT chidluu retinalchangesinanatpinducedmodelofretinaldegeneration AT robynhguymer retinalchangesinanatpinducedmodelofretinaldegeneration AT robertkshepherd retinalchangesinanatpinducedmodelofretinaldegeneration AT ericalucyfletcher retinalchangesinanatpinducedmodelofretinaldegeneration |