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Selective inner retinal dysfunction precedes ganglion cell loss in a mouse glaucoma model.
Br J Ophthalmol. 2008 May; 92(5):683-8.BJ

Abstract

BACKGROUND/AIMS

To correlate ganglion cell function with defined parameters of the elevated intraocular pressure profile (IOP) in a mouse glaucoma model and to determine the temporal relationship of these functional changes with ganglion cell death.

METHODS

Unilateral chronic ocular hypertension was induced in C57BL6/J mice by laser ablation of the limbal episcleral veins. Scotopic flash electroretinograms were recorded after 5, 10, 20, and 40 days to isolate specific outer and inner retinal responses. Inner retinal function was correlated with the pressure differential between treated and non-treated eyes at the time of electroretinographic recording, and with the cumulative IOP insult (the integral of the IOP.time profile). Peripheral and central ganglion cell densities were quantified by Brn-3 immunohistochemistry.

RESULTS

Elevated IOP induced a preferential deficit in inner retinal function. The positive scotopic threshold response (pSTR) was suppressed by 68% on day 5, by 50% on day 10, by 54% on day 20 and by 46% on day 40 after laser treatment. Inhibition of the STR correlated with the pressure differential between treated and non-treated eyes but not with the IOP.time integral. Inner retinal dysfunction preceded the progressive death of ganglion cells. Ganglion cell loss occurred preferentially in peripheral retina and correlated with the cumulative IOP insult.

CONCLUSION

We have demonstrated specific inner retinal dysfunction in an inducible mouse glaucoma model. STRs are sensitive to elevated IOP per se, and their early suppression reflects ganglion cell dysfunction rather than cell death. The correlation between IOP elevation and suppression of inner retinal function, in the context of the temporal progression of ganglion cell death, suggests that a portion of the IOP-mediated ganglion cell dysfunction may be reversible.

Authors+Show Affiliations

School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18296504

Citation

Holcombe, D J., et al. "Selective Inner Retinal Dysfunction Precedes Ganglion Cell Loss in a Mouse Glaucoma Model." The British Journal of Ophthalmology, vol. 92, no. 5, 2008, pp. 683-8.
Holcombe DJ, Lengefeld N, Gole GA, et al. Selective inner retinal dysfunction precedes ganglion cell loss in a mouse glaucoma model. Br J Ophthalmol. 2008;92(5):683-8.
Holcombe, D. J., Lengefeld, N., Gole, G. A., & Barnett, N. L. (2008). Selective inner retinal dysfunction precedes ganglion cell loss in a mouse glaucoma model. The British Journal of Ophthalmology, 92(5), 683-8. https://doi.org/10.1136/bjo.2007.133223
Holcombe DJ, et al. Selective Inner Retinal Dysfunction Precedes Ganglion Cell Loss in a Mouse Glaucoma Model. Br J Ophthalmol. 2008;92(5):683-8. PubMed PMID: 18296504.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective inner retinal dysfunction precedes ganglion cell loss in a mouse glaucoma model. AU - Holcombe,D J, AU - Lengefeld,N, AU - Gole,G A, AU - Barnett,N L, Y1 - 2008/02/22/ PY - 2008/2/26/pubmed PY - 2008/5/23/medline PY - 2008/2/26/entrez SP - 683 EP - 8 JF - The British journal of ophthalmology JO - Br J Ophthalmol VL - 92 IS - 5 N2 - BACKGROUND/AIMS: To correlate ganglion cell function with defined parameters of the elevated intraocular pressure profile (IOP) in a mouse glaucoma model and to determine the temporal relationship of these functional changes with ganglion cell death. METHODS: Unilateral chronic ocular hypertension was induced in C57BL6/J mice by laser ablation of the limbal episcleral veins. Scotopic flash electroretinograms were recorded after 5, 10, 20, and 40 days to isolate specific outer and inner retinal responses. Inner retinal function was correlated with the pressure differential between treated and non-treated eyes at the time of electroretinographic recording, and with the cumulative IOP insult (the integral of the IOP.time profile). Peripheral and central ganglion cell densities were quantified by Brn-3 immunohistochemistry. RESULTS: Elevated IOP induced a preferential deficit in inner retinal function. The positive scotopic threshold response (pSTR) was suppressed by 68% on day 5, by 50% on day 10, by 54% on day 20 and by 46% on day 40 after laser treatment. Inhibition of the STR correlated with the pressure differential between treated and non-treated eyes but not with the IOP.time integral. Inner retinal dysfunction preceded the progressive death of ganglion cells. Ganglion cell loss occurred preferentially in peripheral retina and correlated with the cumulative IOP insult. CONCLUSION: We have demonstrated specific inner retinal dysfunction in an inducible mouse glaucoma model. STRs are sensitive to elevated IOP per se, and their early suppression reflects ganglion cell dysfunction rather than cell death. The correlation between IOP elevation and suppression of inner retinal function, in the context of the temporal progression of ganglion cell death, suggests that a portion of the IOP-mediated ganglion cell dysfunction may be reversible. SN - 1468-2079 UR - https://www.unboundmedicine.com/medline/citation/18296504/Selective_inner_retinal_dysfunction_precedes_ganglion_cell_loss_in_a_mouse_glaucoma_model_ L2 - https://bjo.bmj.com/lookup/pmidlookup?view=long&pmid=18296504 DB - PRIME DP - Unbound Medicine ER -