Brn3a as a Marker of Retinal Ganglion Cells: Qualitative and Quantitative Time Course Studies in Naïve and Optic Nerve–Injured Retinas
Open accessAbstract
PURPOSE: To characterize Brn3a expression in adult albino rat retinal ganglion cells (RGCs) in naïve animals and in animals subjected to complete intraorbital optic nerve transection (IONT) or crush (IONC). METHODS: Rats were divided into three groups, naïve, IONT, and IONC. Two-, 5-, 9-, or 14-day postlesion (dpl) retinas were examined for immunoreactivity for Brn3a. Before the injury, the RGCs were labeled with Fluorogold (FG; Fluorochrome, Corp. Denver, CO). Brn3a retinal expression was also determined by Western blot analysis. The proportion of RGCs double labeled with Brn3a and FG was determined in radial sections. The temporal course of reduction in Brn3a(+) RGCs and FG(+) RGCs induced by IONC or IONT was assessed by quantifying, in the same wholemounts, the number of surviving FG-labeled RGCs and Brn3a(+)RGCs at the mentioned time points. The total number of FG(+)RGCs was automatically counted in naïve and injured retinas (2 and 5 dpl) or estimated by manual quantification in retinas processed at 9 and 14 dpl. All Brn3a immunopositive RGCs were counted using an automatic routine specifically developed for this purpose. This protocol allowed, as well, the investigation of the spatial distribution of these neurons. RESULTS: Brn3a(+) cells were only present in the ganglion cell layer and showed a spatial distribution comparable to that of FG(+) cells. In the naïve retinal wholemounts the mean (mean +/- SEM; n = 14) total number of FG(+)RGCs and Brn3a(+)RGCs was 80,251 +/- 2,210 and 83,449 +/- 4,541, respectively. Whereas in the radial sections, 92.2% of the FG(+)RGCs were also Brn3a(+), 4.4% of the RGCs were Brn3a(+)FG(-) and 3.4% were FG(+)Brn3a(-). Brn3a expression pattern was maintained in injured RGCs. The temporal course of Brn3a(+)RGC and FG(+)RGC loss induced by IONC or IONT followed a similar trend, but Brn3a(+)RGCs loss was detected earlier than that of FG(+)RGCs. Independent of the marker used to detect the RGCs, it was observed that their loss was quicker and more severe after IONT than after IONC. CONCLUSIONS: Brn3a can be used as a reliable, efficient ex vivo marker to identify and quantify RGCs in control and optic nerve-injured retinas.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Brn3a is an RGC-specific marker.
“including RGC visualized with the cell-specific marker Brn3a (brain-specific homeobox/POU domain protein 3A) [41]”
From AMPK hyperactivation promotes dendrite retraction, synaptic loss, and neuronal dysfunction in glaucoma (2021) · cites this paper as [41]
RBPMS is a selective marker for RGC.
“co-localization of anti-pAMPKThr172 with the RGC-specific markers Brn3a or RBPMS [41, 42].”
From AMPK hyperactivation promotes dendrite retraction, synaptic loss, and neuronal dysfunction in glaucoma (2021) · cites this paper as [41]
Cites
Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP
Feng, G., Mellor, R. H., Bernstein, M., Keller-Peck, C., Nguyen, Q. T., Wallace, M., Nerbonne, J. M., Lichtman, J. W., & Sanes, J. R. (2000) · Neuron · doi:10.1016/s0896-6273(00)00084-2 · Cited by 3,042 · see citing works
The Major Cell Populations of the Mouse Retina
Jeon, C.-J., Strettoi, E., & Masland, R. H. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-21-08936.1998 · Cited by 1,429 · see citing works
Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats
Berkelaar, M., Clarke, D., Wang, Y., Bray, G., & Aguayo, A. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-07-04368.1994 · Cited by 814 · see citing works
Mansour-Robaey, S., Clarke, D. B., Wang, Y. C., Bray, G. M., & Aguayo, A. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.5.1632 · Cited by 731 · see citing works
Vidal‐Sanz, M., Bray, G., Villegas‐Pérez, M. P., et al. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-09-02894.1987 · Cited by 588 · see citing works
Self-citationVillegas‐Pérez, M., Vidal‐Sanz, M., Rasminsky, M., Bray, G. M., & Aguayo, A. J. (1993) · Journal of Neurobiology · doi:10.1002/neu.480240103 · Cited by 455 · see citing works
Self-citationPostnatal changes in retinal ganglion cell and optic axon populations in the pigmented rat
Perry, V. H., Henderson, Z., & Linden, R. (1983) · The Journal of Comparative Neurology · doi:10.1002/cne.902190309 · Cited by 438 · see citing works
Current concepts in neuroanatomical tracing
Köbbert, C., Apps, R., Bechmann, I., Lanciego, J. L., Mey, J., & Thanos, S. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00019-8 · Cited by 419 · see citing works
Progressive Ganglion Cell Degeneration Precedes Neuronal Loss in a Mouse Model of Glaucoma
Buckingham, B. P., Inman, D. M., Lambert, W. S., Oglesby, E., Calkins, D. J., Steele, M. R., Vetter, M. L., Marsh‐Armstrong, N., & Horner, P. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4443-07.2008 · Cited by 415 · see citing works
Villegas‐Pérez, M. P., Vidal‐Sanz, M., Bray, G., & Aguayo, A. (1988) · Journal of Neuroscience · doi:10.1523/jneurosci.08-01-00265.1988 · Cited by 403 · see citing works
Self-citationRamon, P. P., Salvador, M., Villegas-Pérez, M. P., & Vidal‐Sanz, M. (1996) · PubMed · Cited by 399 · see citing works
Self-citationEvidence for an amacrine cell system in the ganglion cell layer of the rat retina
Perry, V. H. (1981) · Neuroscience · doi:10.1016/0306-4522(81)90174-3 · Cited by 396 · see citing works
Xiang, M., Zhou, L., Macke, J. P., Yoshioka, T., Hendry, S., Eddy, R. L., Shows, T. B., & Nathans, J. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-07-04762.1995 · Cited by 394 · see citing works
Thy-1 antigen: A ganglion cell specific marker in rodent retina
Barnstable, C. J., & Dräger, U. C. (1984) · Neuroscience · doi:10.1016/0306-4522(84)90195-7 · Cited by 309 · see citing works
Ganglion cell distribution in the retina of the mouse.
Dräger, U. C., & Olsen, J. F. (1981) · PubMed · Cited by 262 · see citing works
Levkovitch-Verbin, H., Quigley, H. A., Martin, K. R. G., Zack, D. J., Pease, M. E., & Valenta, D. F. (2003) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.02-0646 · Cited by 189 · see citing works
Salinas‐Navarro, M., Mayor-Torroglosa, S., Jiménez-López, M., Avilés‐Trigueros, M., Holmes, T. M., Lund, R. D., Villegas‐Pérez, M. P., & Vidal‐Sanz, M. (2008) · Vision Research · doi:10.1016/j.visres.2008.09.029 · Cited by 181 · see citing works
Self-citationPersistent retrograde labeling of adult rat retinal ganglion cells with the carbocyanine dye diI
Vidal‐Sanz, M., Villegas‐Pérez, M. P., Bray, G. M., et al. (1988) · Experimental Neurology · doi:10.1016/0014-4886(88)90081-7 · Cited by 179 · see citing works
Self-citationChanges in Thy1 gene expression associated with damaged retinal ganglion cells.
Schlamp, C. L., Johnson, E. C., Li, Y., et al. (2001) · PubMed · Cited by 178 · see citing works
Quina, L. A., Pak, W., Lanier, J., Banwait, P., Gratwick, K., Liu, Y., Velasquez, T., O’Leary, D. D. M., Goulding, M., & Turner, E. E. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2837-05.2005 · Cited by 170 · see citing works
Salinas‐Navarro, M., Jiménez-López, M., Valiente‐Soriano, F. J., Alarcón-Martínez, L., Avilés‐Trigueros, M., Mayor, S., Holmes, T. M., Lund, R. D., Villegas-Pérez, M. P., & Vidal‐Sanz, M. (2009) · Vision Research · doi:10.1016/j.visres.2009.01.010 · Cited by 155 · see citing works
Self-citationKo, M., Hu, D., Ritch, R. H., Sharma, S. C., & Chen, C. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)01830-4 · Cited by 151 · see citing works
Johnson, T. V., & Martin, K. R. G. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.07-1601 · Cited by 144 · see citing works
Lafuente, M. P., Villegas‐Pérez, M. P., Sellés-Navarro, I., et al. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00458-4 · Cited by 142 · see citing works
Bray, G. M., Villegas‐Pérez, M. P., Vidal‐Sanz, M., & Aguayo, A. J. (1987) · Journal of Experimental Biology · doi:10.1242/jeb.132.1.5 · Cited by 138 · see citing works
Self-citationAntibodies to heavy neurofilament subunit detect a subpopulation of damaged ganglion cells in retina
Dräger, U. C., & Hofbauer, A. (1984) · Nature · doi:10.1038/309624a0 · Cited by 134 · see citing works
Wang, S. W., Mu, X., Bowers, W. J., Kim, D.-S., Plas, D. T., Crair, M. C., Federoff, H. J., Gan, L., & Klein, W. H. (2002) · Development · doi:10.1242/dev.129.2.467 · Cited by 134 · see citing works
Canola, K., Angénieux, B., Tekaya, M., Quiambao, A. B., Naash, M. I., Munier, F. L., Schorderet, D. F., & Arsenijévic, Y. (2006) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0190 · Cited by 114 · see citing works
Agudo‐Barriuso, M., Pérez-Marín, M. C., Lönngren, U., Sobrado, P., Conesa, A., Cánovas, I., Salinas‐Navarro, M., Miralles-Imperial, J., Hallböök, F., & Vidal‐Sanz, M. (2008) · PubMed Central · Cited by 112 · see citing works
Self-citationGamma-synuclein as a marker of retinal ganglion cells.
Surgucheva, I. G., Weisman, A., Goldberg, J. L., Shnyra, A. A., & Surguchov, A. P. (2008) · PubMed Central · Cited by 108 · see citing works
Downregulation of Thy1 in Retinal Ganglion Cells in Experimental Glaucoma
Huang, W. C., Fileta, J. B., Guo, Y. P., et al. (2006) · Current Eye Research · doi:10.1080/02713680500545671 · Cited by 108 · see citing works
Lafuente, M. P., Villegas‐Pérez, M. P., Sobrado‐Calvo, P., et al. (2001) · PubMed · Cited by 92 · see citing works
Self-citationRetinal Ganglion Cell Death Induced by Retinal Ischemia
Vidal‐Sanz, M., Lafuente, M. P., Mayor, S., et al. (2001) · Survey of Ophthalmology · doi:10.1016/s0039-6257(01)00205-3 · Cited by 90 · see citing works
Self-citationIs Thy-1 expressed only by ganglion cells and their axons in the retina and optic nerve?
Perry, V. H., Morris, R. J., & Raisman, G. (1984) · Journal of Neurocytology · doi:10.1007/bf01148495 · Cited by 84 · see citing works
Raymond, I., Vila, A., Huynh, U.-C. N., & Brecha, N. C. (2008) · PubMed Central · Cited by 82 · see citing works
Agudo‐Barriuso, M., Pérez-Marín, M. C., Sobrado‐Calvo, P., ̈nngren, U. L., Salinas‐Navarro, M., Cánovas, I., Nadal-Nicolás, F. M., Miralles-Imperial, J., Hallböök, F., & Vidal‐Sanz, M. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-2404 · Cited by 81 · see citing works
Self-citationProgressive optic axon dystrophy and vacuslar changes in rd mice.
Wang, S., Villegas‐Pérez, M. P., Vidal‐Sanz, M., & Lund, R. D. (2000) · PubMed · Cited by 79 · see citing works
Self-citationCharacterization of retinal damage in the episcleral vein cauterization rat glaucoma model
Danias, J., Shen, F., Kavalarakis, M., et al. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2005.06.013 · Cited by 78 · see citing works
Lafuente, M. P., Villegas‐Pérez, M. P., Mayor, S., et al. (2002) · Experimental Eye Research · doi:10.1006/exer.2001.1122 · Cited by 76 · see citing works
Death and neuroprotection of retinal ganglion cells after different types of injury
Vidal‐Sanz, M., Lafuente, M. P., Sobrado‐Calvo, P., et al. (2000) · Neurotoxicity Research · doi:10.1007/bf03033795 · Cited by 75 · see citing works
Self-citationMeasurement of retinal injury in the rat after optic nerve transection: an RT-PCR study.
Chidlow, G., Casson, R. J., Sobrado‐Calvo, P., et al. (2005) · PubMed · Cited by 72 · see citing works
Self-citationHudson, C. D., Morris, P. J., Latchman, D. S., & Budhram-Mahadeo, V. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408679200 · Cited by 68 · see citing works
Mechanism of retinal ganglion cell loss in inherited retinal dystrophy
Villegas‐Pérez, M. P., Vidal‐Sanz, M., & Lund, R. D. (1996) · Neuroreport · doi:10.1097/00001756-199608120-00028 · Cited by 65 · see citing works
Self-citationThanos, S., Vidal‐Sanz, M., & Aguayo, A. J. (1987) · Brain Research · doi:10.1016/0006-8993(87)90799-2 · Cited by 55 · see citing works
Self-citationBudhram-Mahadeo, V. S., Morris, P. J., & Latchman, D. S. (2002) · Oncogene · doi:10.1038/sj.onc.1205842 · Cited by 53 · see citing works
Total Retinal Nitric Oxide Production is Increased in Intraocular Pressure-elevated Rats
Siu, A. L. (2002) · Experimental Eye Research · doi:10.1016/s0014-4835(02)92029-4 · Cited by 49 · see citing works
Rat retinal müller cells express Thy‐1 following neuronal cell death
Dabin, I., & Barnstable, C. J. (1995) · Glia · doi:10.1002/glia.440140105 · Cited by 41 · see citing works
The Brn-3a transcription factor
Latchman, D. S. (1998) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(98)00090-9 · Cited by 38 · see citing works
Analysis of optic nerve stroke by retinal Bex expression.
Bernstein, S. L., Koo, J. H., Slater, B. J., et al. (2006) · PubMed · Cited by 35 · see citing works
Efficient estimation of retinal ganglion cell number: A stereological approach
Fileta, J. B., Huang, W. C., Kwon, G. P., Filippopoulos, T., Ben, Y., Dobberfuhl, A., & Grosskreutz, C. L. (2007) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2007.12.008 · Cited by 33 · see citing works
Neuroprotection of retinal ganglion cell function and their central nervous system targets
Vidal‐Sanz, M., de la Villa, P., Avilés‐Trigueros, M., et al. (2007) · Eye · doi:10.1038/sj.eye.6702888 · Cited by 25 · see citing works
Self-citationRegulation of Hsp27 expression and cell survival by the POU transcription factor Brn3a
Farooqui-Kabir, S., Budhram-Mahadeo, V. S., Lewis, H., et al. (2004) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401478 · Cited by 24 · see citing works
Microtubule-associated protein 1A (MAP 1A) is a ganglion cell marker in adult rat retina
McKerracher, L. J., Vallee, R. B., & Aguayo, A. J. (1989) · Visual Neuroscience · doi:10.1017/s0952523800002157 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The RNA binding protein RBPMS is a selective marker of ganglion cells in the mammalian retina
Rodriguez, A. R., de Sevilla Müller, L. P., & Brecha, N. C. (2014) · Journal of Comparative Neurology · doi:10.1002/cne.23521 · Cited by 483 · see citing works
Sterling, J. K., Adetunji, M. O., Guttha, S., Bargoud, A. R., Uyhazi, K. E., Ross, A. G., Dunaief, J. L., & Cui, Q. N. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108271 · Cited by 148 · see citing works
Sayyad, Z., Sirohi, K., Radha, V., & Swarup, G. (2017) · Scientific Reports · doi:10.1038/s41598-017-17241-0 · Cited by 96 · see citing works
Cwerman-Thibault, H., Augustin, S., Lechauve, C., Ayache, J., Ellouze, S., Sahel, J.-A., & Corral-Debrinski, M. (2015) · Molecular Therapy - Methods & Clinical Development · doi:10.1038/mtm.2015.3 · Cited by 86 · see citing works
Madeira, M. H., Boia, R., Elvas, F., Martins, T., Cunha, R. A., Ambrósio, A. F., & Santiago, A. R. (2016) · Translational Research · doi:10.1016/j.trsl.2015.11.005 · Cited by 83 · see citing works
Hwang, C. K., Chaurasia, S. S., Jackson, C. R., Chan, G. C.-K., Storm, D. R., & Iuvone, P. M. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2039-13.2013 · Cited by 81 · see citing works
Belforte, N., Agostinone, J., Alarcon-Martinez, L., Villafranca-Baughman, D., Dotigny, F., Cueva Vargas, J. L., & Di Polo, A. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00466-z · Cited by 67 · see citing works
“Robust mTORC1 activity, visualized through co-labeling of pS6Ser240/244 and RBPMS, was found in non-injured RGC (Fig.”
BackgroundMethodInfluentialSaidha, S., Green, A. J., Leocani, L., Vidal-Jordana, A., Kenney, R. C., Bsteh, G., Outteryck, O., Thompson, A., Montalban, X., Coetzee, T., et al. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(25)00275-3 · Cited by 66 · see citing works
REDD2-mediated inhibition of mTOR promotes dendrite retraction induced by axonal injury
Morquette, B., Morquette, P., Agostinone, J., Feinstein, E., McKinney, R. A., Kolta, A., & Di Polo, A. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.149 · Cited by 60 · see citing works
ERG changes in albino and pigmented mice after optic nerve transection
Alarcón-Martínez, L., Avilés-Trigueros, M., Galindo-Romero, C., Valiente-Soriano, J., Agudo-Barriuso, M., Villa, P. D. L., Villegas-Pérez, M. P., & Vidal-Sanz, M. (2010) · Vision Research · doi:10.1016/j.visres.2010.08.014 · Cited by 61 · see citing works
Self-citationA novel retinal ganglion cell promoter for utility in AAV vectors
Hanlon, K. S., Chadderton, N., Palfi, A., Blanco Fernandez, A., Humphries, P., Kenna, P. F., Millington-Ward, S., & Farrar, G. J. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00521 · Cited by 34 · see citing works
Sarrazin, N., Chavret-Reculon, E., Bachelin, C., Felfli, M., Arab, R., Gilardeau, S., Brazhnikova, E., Dubus, E., Yahia Cherif, L., Lorenceau, J., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2115973119 · Cited by 15 · see citing works
- Authors
- Nadal-Nicola´s, F. M., Jime´nez-Lo´pez, M., Sobrado-Calvo, P., Nieto-Lo´pez, L., Ca´novas-Marti´nez, I., Salinas-Navarro, M., Vidal-Sanz, M., & Agudo, M.
- Affiliations
- From Departamento de Oftalmologi´a, Facultad de Medicina, Campus Espinardo, Universidad de Murcia, Murcia, Spain;2Servicio Murciano de Salud. Hospital Universitario Virgen de la Arrixaca, Fundacio´n para la Formacio´n e Investigacio´n Sanitarias de la Reg
- From Departamento de Oftalmologi´a, Facultad de Medicina, Campus Espinardo, Universidad de Murcia, Murcia, Spain;
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2009-08-01
- Volume
- 50
- Issue
- 8
- Pages
- 3860
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2039127036
- Cited by
- 541
- References
- 53
- Citations by year
- 2026: 18 · 2025: 28 · 2024: 30 · 2023: 28 · 2022: 36 · 2021: 34 · 2020: 37 · 2019: 36 · 2018: 36 · 2017: 29 · 2016: 40 · 2015: 41 · 2014: 42 · 2013: 31 · 2012: 23
- FWCI
- 25.41
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc-nd
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- Hispana (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- retinal ganglion cells, optic nerve injury, optic nerve transection, optic nerve crush, ganglion cell survival, retinal ganglion cell layer, retinal wholemounts, retinal gene expression, axon regeneration, retinal degeneration
- MeSH terms
- Animals, Cell Count, Female, Fluorescent Dyes, Microscopy, Fluorescence, Nerve Crush, Retina, Retinal Ganglion Cells, Stilbamidines, Time Factors, Blotting, Western, Biomarkers, Rats, Sprague-Dawley, Fluorescent Antibody Technique, Indirect, Optic Nerve Injuries, Transcription Factor Brn-3A, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
