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Retinal ganglion cell loss in a rat ocular hypertension model is sectorial and involves early optic nerve axon loss.
Invest Ophthalmol Vis Sci. 2011 Jan; 52(1):434-41.IO

Abstract

PURPOSE

Previous analyses of the DBA/2J mouse glaucoma model show a sectorial degeneration pattern suggestive of an optic nerve head insult. In addition, there are large numbers of retinal ganglion cells (RGCs) that cannot be retrogradely labeled but maintain RGC gene expression, and many of these have somatic phosphorylated neurofilament labeling. Here the authors further elucidate these features of glaucomatous degeneration in a rat ocular hypertension model.

METHODS

IOP was elevated in Wistar rats by translimbal laser photocoagulation. Retina whole mounts were analyzed for Sncg mRNA in situ hybridization, fluorogold (FG) retrograde labeling, and immunohistochemistry for phosphorylated neurofilaments (pNF) at 10 and 29 days after IOP increase. A novel automatic method was used to estimate axon numbers in plastic sections of optic nerves.

RESULTS

Sncg mRNA was confirmed as a specific marker for RGCs in rat. Loss of RGCs after IOP elevation occurred in sectorial patterns. Sectors amid degeneration contained RGCs that were likely disconnected because these had pNF in their somas and dendrites, were not labeled by FG, and were associated with reactive plasticity within the retina. Most of the axon loss within the optic nerve already occurred by 10 days after the onset of IOP elevation.

CONCLUSIONS

These data demonstrate that the pattern of RGC loss after laser-induced ocular hypertension in rats is similar to that previously reported in DBA/2J mice. The results support the view that in glaucoma RGC axons are damaged at the optic nerve head and degenerate within the optic nerve before there is loss of RGC somas.

Authors+Show Affiliations

Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20811062

Citation

Soto, Ileana, et al. "Retinal Ganglion Cell Loss in a Rat Ocular Hypertension Model Is Sectorial and Involves Early Optic Nerve Axon Loss." Investigative Ophthalmology & Visual Science, vol. 52, no. 1, 2011, pp. 434-41.
Soto I, Pease ME, Son JL, et al. Retinal ganglion cell loss in a rat ocular hypertension model is sectorial and involves early optic nerve axon loss. Invest Ophthalmol Vis Sci. 2011;52(1):434-41.
Soto, I., Pease, M. E., Son, J. L., Shi, X., Quigley, H. A., & Marsh-Armstrong, N. (2011). Retinal ganglion cell loss in a rat ocular hypertension model is sectorial and involves early optic nerve axon loss. Investigative Ophthalmology & Visual Science, 52(1), 434-41. https://doi.org/10.1167/iovs.10-5856
Soto I, et al. Retinal Ganglion Cell Loss in a Rat Ocular Hypertension Model Is Sectorial and Involves Early Optic Nerve Axon Loss. Invest Ophthalmol Vis Sci. 2011;52(1):434-41. PubMed PMID: 20811062.
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TY - JOUR T1 - Retinal ganglion cell loss in a rat ocular hypertension model is sectorial and involves early optic nerve axon loss. AU - Soto,Ileana, AU - Pease,Mary E, AU - Son,Janice L, AU - Shi,Xiaohai, AU - Quigley,Harry A, AU - Marsh-Armstrong,Nicholas, Y1 - 2011/01/21/ PY - 2010/9/3/entrez PY - 2010/9/3/pubmed PY - 2011/2/26/medline SP - 434 EP - 41 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 52 IS - 1 N2 - PURPOSE: Previous analyses of the DBA/2J mouse glaucoma model show a sectorial degeneration pattern suggestive of an optic nerve head insult. In addition, there are large numbers of retinal ganglion cells (RGCs) that cannot be retrogradely labeled but maintain RGC gene expression, and many of these have somatic phosphorylated neurofilament labeling. Here the authors further elucidate these features of glaucomatous degeneration in a rat ocular hypertension model. METHODS: IOP was elevated in Wistar rats by translimbal laser photocoagulation. Retina whole mounts were analyzed for Sncg mRNA in situ hybridization, fluorogold (FG) retrograde labeling, and immunohistochemistry for phosphorylated neurofilaments (pNF) at 10 and 29 days after IOP increase. A novel automatic method was used to estimate axon numbers in plastic sections of optic nerves. RESULTS: Sncg mRNA was confirmed as a specific marker for RGCs in rat. Loss of RGCs after IOP elevation occurred in sectorial patterns. Sectors amid degeneration contained RGCs that were likely disconnected because these had pNF in their somas and dendrites, were not labeled by FG, and were associated with reactive plasticity within the retina. Most of the axon loss within the optic nerve already occurred by 10 days after the onset of IOP elevation. CONCLUSIONS: These data demonstrate that the pattern of RGC loss after laser-induced ocular hypertension in rats is similar to that previously reported in DBA/2J mice. The results support the view that in glaucoma RGC axons are damaged at the optic nerve head and degenerate within the optic nerve before there is loss of RGC somas. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/20811062/Retinal_ganglion_cell_loss_in_a_rat_ocular_hypertension_model_is_sectorial_and_involves_early_optic_nerve_axon_loss_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.10-5856 DB - PRIME DP - Unbound Medicine ER -