Tags

Type your tag names separated by a space and hit enter

Optic nerve dynein motor protein distribution changes with intraocular pressure elevation in a rat model of glaucoma.
Exp Eye Res. 2006 Aug; 83(2):255-62.EE

Abstract

Acute intraocular pressure (IOP) elevation causes accumulation of retrogradely-transported brain derived neurotrophic factor and its receptor at the optic nerve head (ONH) in rats and monkeys. Obstruction of axonal transport may therefore be involved in glaucoma pathogenesis, but it is unknown if obstruction is specific to certain transported factors or represents a generalized failure of retrograde axonal transport. The dynein motor complex mediates retrograde axonal transport in retinal ganglion cells (RGC). Our hypothesis was that elevated IOP interferes with dynein-mediated axonal transport. We studied the distribution of dynein subunits in the retina and optic nerve after acute and chronic experimental IOP elevation in the rat. IOP was elevated unilaterally in 54 rats. Dynein subunit distribution was compared in treated and control eyes by immunohistochemistry and Western blotting at 1 day (n=12), 3 days (n=4), 1 week (n=15), 2 weeks (n=12) and 4 weeks (n=11). For immunohistochemistry, sections through the ONH were probed with an anti-dynein heavy chain (HC) antibody and graded semi-quantitatively by masked observers. Other freshly enucleated eyes were microdissected for separate Western blot quantification of dynein intermediate complex (IC) in myelinated and unmyelinated optic nerve, ONH and retina. Immunohistochemistry showed accumulation of dynein HC at the ONH in IOP elevation eyes compared to controls (P<0.001, Wilcoxon paired sign-rank test, n=29). ONH dynein IC was elevated by 46.5% in chronic IOP elevation eyes compared to controls by Western blotting (P<0.001, 95% CI=25.9% to 67.8%, n=17). The maximum increase in ONH dynein IC was 78.7% after 1 week (P<0.05, n=5), but significant increases were also detected after 4 h and 4 weeks of IOP elevation (P<0.05, n=4 rats per group). Total retinal dynein IC was increased by 8.7% in chronic IOP elevation eyes compared to controls (P<0.03, 95% CI 1.4% to 16.1%, n=24). In the retina, IOP elevation particularly affected the 72 kD subunit of dynein IC, which was 100.7% higher in chronic IOP elevation eyes compared to controls (P<0.00001, 95% CI 71.0% to 130.4%, n=21). Dynein IC changes in myelinated and unmyelinated optic nerve were not significant (P>0.05). We conclude that dynein accumulates at the ONH with experimental IOP elevation in the rat, supporting the hypothesis that disrupted axonal transport in RGC may be involved in the pathogenesis of glaucoma. The effect of IOP elevation on other motor proteins deserves further investigation in the future.

Authors+Show Affiliations

Glaucoma Research Laboratory, Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA. kmartin1@doctors.org.ukNo 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

16546168

Citation

Martin, Keith R G., et al. "Optic Nerve Dynein Motor Protein Distribution Changes With Intraocular Pressure Elevation in a Rat Model of Glaucoma." Experimental Eye Research, vol. 83, no. 2, 2006, pp. 255-62.
Martin KR, Quigley HA, Valenta D, et al. Optic nerve dynein motor protein distribution changes with intraocular pressure elevation in a rat model of glaucoma. Exp Eye Res. 2006;83(2):255-62.
Martin, K. R., Quigley, H. A., Valenta, D., Kielczewski, J., & Pease, M. E. (2006). Optic nerve dynein motor protein distribution changes with intraocular pressure elevation in a rat model of glaucoma. Experimental Eye Research, 83(2), 255-62.
Martin KR, et al. Optic Nerve Dynein Motor Protein Distribution Changes With Intraocular Pressure Elevation in a Rat Model of Glaucoma. Exp Eye Res. 2006;83(2):255-62. PubMed PMID: 16546168.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Optic nerve dynein motor protein distribution changes with intraocular pressure elevation in a rat model of glaucoma. AU - Martin,Keith R G, AU - Quigley,Harry A, AU - Valenta,Danielle, AU - Kielczewski,Jennifer, AU - Pease,Mary Ellen, Y1 - 2006/03/20/ PY - 2005/01/11/received PY - 2005/06/26/revised PY - 2005/11/30/accepted PY - 2006/3/21/pubmed PY - 2006/9/16/medline PY - 2006/3/21/entrez SP - 255 EP - 62 JF - Experimental eye research JO - Exp Eye Res VL - 83 IS - 2 N2 - Acute intraocular pressure (IOP) elevation causes accumulation of retrogradely-transported brain derived neurotrophic factor and its receptor at the optic nerve head (ONH) in rats and monkeys. Obstruction of axonal transport may therefore be involved in glaucoma pathogenesis, but it is unknown if obstruction is specific to certain transported factors or represents a generalized failure of retrograde axonal transport. The dynein motor complex mediates retrograde axonal transport in retinal ganglion cells (RGC). Our hypothesis was that elevated IOP interferes with dynein-mediated axonal transport. We studied the distribution of dynein subunits in the retina and optic nerve after acute and chronic experimental IOP elevation in the rat. IOP was elevated unilaterally in 54 rats. Dynein subunit distribution was compared in treated and control eyes by immunohistochemistry and Western blotting at 1 day (n=12), 3 days (n=4), 1 week (n=15), 2 weeks (n=12) and 4 weeks (n=11). For immunohistochemistry, sections through the ONH were probed with an anti-dynein heavy chain (HC) antibody and graded semi-quantitatively by masked observers. Other freshly enucleated eyes were microdissected for separate Western blot quantification of dynein intermediate complex (IC) in myelinated and unmyelinated optic nerve, ONH and retina. Immunohistochemistry showed accumulation of dynein HC at the ONH in IOP elevation eyes compared to controls (P<0.001, Wilcoxon paired sign-rank test, n=29). ONH dynein IC was elevated by 46.5% in chronic IOP elevation eyes compared to controls by Western blotting (P<0.001, 95% CI=25.9% to 67.8%, n=17). The maximum increase in ONH dynein IC was 78.7% after 1 week (P<0.05, n=5), but significant increases were also detected after 4 h and 4 weeks of IOP elevation (P<0.05, n=4 rats per group). Total retinal dynein IC was increased by 8.7% in chronic IOP elevation eyes compared to controls (P<0.03, 95% CI 1.4% to 16.1%, n=24). In the retina, IOP elevation particularly affected the 72 kD subunit of dynein IC, which was 100.7% higher in chronic IOP elevation eyes compared to controls (P<0.00001, 95% CI 71.0% to 130.4%, n=21). Dynein IC changes in myelinated and unmyelinated optic nerve were not significant (P>0.05). We conclude that dynein accumulates at the ONH with experimental IOP elevation in the rat, supporting the hypothesis that disrupted axonal transport in RGC may be involved in the pathogenesis of glaucoma. The effect of IOP elevation on other motor proteins deserves further investigation in the future. SN - 0014-4835 UR - https://www.unboundmedicine.com/medline/citation/16546168/Optic_nerve_dynein_motor_protein_distribution_changes_with_intraocular_pressure_elevation_in_a_rat_model_of_glaucoma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(06)00127-8 DB - PRIME DP - Unbound Medicine ER -