Tags

Type your tag names separated by a space and hit enter

BDNF Rescues RGCs But Not Intrinsically Photosensitive RGCs in Ocular Hypertensive Albino Rat Retinas.
Invest Ophthalmol Vis Sci. 2015 Feb 26; 56(3):1924-36.IO

Abstract

PURPOSE

To study the responses of the general population of retinal ganglion cells (Brn3a(+)RGCs) versus the intrinsically photosensitive RGCs (melanopsin-expressing RGCs [m(+)RGCs]) to ocular hypertension (OHT), the effects of brain-derived neurotrophic factor (BDNF) on the survival of axonally intact and axonally nonintact RGCs, and the correlation of vascular integrity with sectorial RGC loss.

METHODS

In Sprague-Dawley rats, 5 μg BDNF or vehicle was intravitreally injected into the left eye followed by laser photocoagulation of the limbal tissues. To identify RGCs with an active retrograde axonal transport, Fluorogold was applied to both superior colliculi 1 week before euthanasia (FG(+)RGCs). Retinas were dissected 12 or 15 days after lasering and immunoreacted against Brn3a (to identify all RGCs except m(+)RGCs), melanopsin, or RECA1 (inner retinal vasculature).

RESULTS

Ocular hypertension resulted at 12 to 15 days in sectorial loss of FG(+)RGCs (78%-84%, respectively) while Brn3a(+)RGCs were significantly greater, indicating that a substantial proportion (approximately 21%-26%) of RGCs with their retrograde axonal transport impaired survive in the retina. Brain-derived neurotrophic factor increased the survival of Brn3a(+)RGCs to 81% to 67% at 12 to 15 days, respectively. The inner retinal vasculature showed no abnormalities that could account for the sectorial loss of RGCs. At 12 to 15 days, m(+)RGCs decreased to approximately 50% to 51%, but this loss was diffuse across the retina and was not prevented by BDNF.

CONCLUSIONS

The responses of m(+)RGCs against OHT-induced retinal degeneration and neuroprotection differ from those of Brn3a(+)RGCs; while OHT induces similar loss of Brn3a(+)RGCs and m(+)RGCs, Brn3a(+)RGCs are lost in sectors and can be rescued with BDNF, but m(+)RGCs do not respond to BDNF and their loss is diffuse.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Valiente-Soriano FJ
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Nadal-Nicolás FM
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Salinas-Navarro M
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Jiménez-López M
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Bernal-Garro JM
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Villegas-Pérez MP
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Agudo-Barriuso M
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.
Vidal-Sanz M
Departamento de Oftalmología, Facultad de Medicina, Universidad de Murcia, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), Murcia, Spain.

MeSH

AnimalsBrain-Derived Neurotrophic FactorCell DeathDisease Models, AnimalFemaleIntraocular PressureIntravitreal InjectionsLasersOcular HypertensionPhotoreceptor Cells, VertebrateRatsRats, Sprague-DawleyRetinaRetinal Ganglion CellsRod OpsinsTranscription Factor Brn-3A

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25722208

Citation

Valiente-Soriano, Francisco J., et al. "BDNF Rescues RGCs but Not Intrinsically Photosensitive RGCs in Ocular Hypertensive Albino Rat Retinas." Investigative Ophthalmology & Visual Science, vol. 56, no. 3, 2015, pp. 1924-36.
Valiente-Soriano FJ, Nadal-Nicolás FM, Salinas-Navarro M, et al. BDNF Rescues RGCs But Not Intrinsically Photosensitive RGCs in Ocular Hypertensive Albino Rat Retinas. Invest Ophthalmol Vis Sci. 2015;56(3):1924-36.
Valiente-Soriano, F. J., Nadal-Nicolás, F. M., Salinas-Navarro, M., Jiménez-López, M., Bernal-Garro, J. M., Villegas-Pérez, M. P., Agudo-Barriuso, M., & Vidal-Sanz, M. (2015). BDNF Rescues RGCs But Not Intrinsically Photosensitive RGCs in Ocular Hypertensive Albino Rat Retinas. Investigative Ophthalmology & Visual Science, 56(3), 1924-36. https://doi.org/10.1167/iovs.15-16454
Valiente-Soriano FJ, et al. BDNF Rescues RGCs but Not Intrinsically Photosensitive RGCs in Ocular Hypertensive Albino Rat Retinas. Invest Ophthalmol Vis Sci. 2015 Feb 26;56(3):1924-36. PubMed PMID: 25722208.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BDNF Rescues RGCs But Not Intrinsically Photosensitive RGCs in Ocular Hypertensive Albino Rat Retinas. AU - Valiente-Soriano,Francisco J, AU - Nadal-Nicolás,Francisco M, AU - Salinas-Navarro,Manuel, AU - Jiménez-López,Manuel, AU - Bernal-Garro,Jose M, AU - Villegas-Pérez,Maria P, AU - Agudo-Barriuso,Marta, AU - Vidal-Sanz,Manuel, Y1 - 2015/02/26/ PY - 2015/2/28/entrez PY - 2015/2/28/pubmed PY - 2015/8/26/medline KW - BDNF neuroprotection KW - Brn3a KW - Fluorogold KW - adult albino rats KW - axonal transport KW - experimental glaucoma KW - intrinsically photosensitive RGCs KW - laser-induced ocular hypertension KW - melanopsin KW - melanopsin retinal ganglion cells KW - ocular hypertension KW - spatial distribution SP - 1924 EP - 36 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 56 IS - 3 N2 - PURPOSE: To study the responses of the general population of retinal ganglion cells (Brn3a(+)RGCs) versus the intrinsically photosensitive RGCs (melanopsin-expressing RGCs [m(+)RGCs]) to ocular hypertension (OHT), the effects of brain-derived neurotrophic factor (BDNF) on the survival of axonally intact and axonally nonintact RGCs, and the correlation of vascular integrity with sectorial RGC loss. METHODS: In Sprague-Dawley rats, 5 μg BDNF or vehicle was intravitreally injected into the left eye followed by laser photocoagulation of the limbal tissues. To identify RGCs with an active retrograde axonal transport, Fluorogold was applied to both superior colliculi 1 week before euthanasia (FG(+)RGCs). Retinas were dissected 12 or 15 days after lasering and immunoreacted against Brn3a (to identify all RGCs except m(+)RGCs), melanopsin, or RECA1 (inner retinal vasculature). RESULTS: Ocular hypertension resulted at 12 to 15 days in sectorial loss of FG(+)RGCs (78%-84%, respectively) while Brn3a(+)RGCs were significantly greater, indicating that a substantial proportion (approximately 21%-26%) of RGCs with their retrograde axonal transport impaired survive in the retina. Brain-derived neurotrophic factor increased the survival of Brn3a(+)RGCs to 81% to 67% at 12 to 15 days, respectively. The inner retinal vasculature showed no abnormalities that could account for the sectorial loss of RGCs. At 12 to 15 days, m(+)RGCs decreased to approximately 50% to 51%, but this loss was diffuse across the retina and was not prevented by BDNF. CONCLUSIONS: The responses of m(+)RGCs against OHT-induced retinal degeneration and neuroprotection differ from those of Brn3a(+)RGCs; while OHT induces similar loss of Brn3a(+)RGCs and m(+)RGCs, Brn3a(+)RGCs are lost in sectors and can be rescued with BDNF, but m(+)RGCs do not respond to BDNF and their loss is diffuse. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/25722208/BDNF_Rescues_RGCs_But_Not_Intrinsically_Photosensitive_RGCs_in_Ocular_Hypertensive_Albino_Rat_Retinas_ DB - PRIME DP - Unbound Medicine ER -