Distortion of axonal cytoskeleton: An early sign of glaucomatous damage

XiangRun Huang, Wei Kong, Ye Zhou, Giovanni Gregori

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

PURPOSE. Glaucoma damages the retinal nerve fiber layer (RNFL). The purpose of this study was to investigate the distribution of major cytoskeleton components, F-actin, microtubules (MTs), and neurofilaments (NFs), in the RNFL during the development of glaucoma. METHODS. Intraocular hypertension was induced in a rat model by laser photocoagulation of the trabecular meshwork. Retinas were obtained after 2 to 3.5 weeks of treatment. Multiple fluorescent stains were used to identify F-actin, MTs, NFs, and nuclei simultaneously in the same tissue. Distribution of these components in a whole-mounted retina was examined by confocal microscopy. Fluorescent stain was quantitatively described. RESULTS. In normal RNFL F-actin, MTs, and NFs were intensely stained. Along the bundles, F-actin and MTs were strongly colocalized, but alternating strands of F-actin and NFs were apparent. Normal RNFL lacked nuclei. In glaucomatous retinas, irregular staining of F-actin, MTs, and NFs was found within the bundles. A strong network of F-actin appeared on the RNFL surface and between the bundles. In severely damaged retinal regions total loss of F-actin and MTs was found, whereas residual strands of NFs were evident. Before the decrease in RNFL thickness, irregularity of F-actin stain and density of nuclei in the RNFL significantly increased. CONCLUSIONS. The results suggest that F-actin, MTs, and NFs are rich and approximately uniformly distributed in the normal RNFL. Glaucoma causes alteration of the cytoskeleton in the RNFL. F-actin is the most sensitive component in its response to stress on the retina. An increase in the number of nuclei in the RNFL may be an early sign of glaucomatous damage.

Original languageEnglish
Pages (from-to)2879-2888
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number6
DOIs
StatePublished - May 1 2011

Fingerprint

Cytoskeleton
Nerve Fibers
Actins
Intermediate Filaments
Microtubules
Retina
Glaucoma
Coloring Agents
Trabecular Meshwork
Light Coagulation
Confocal Microscopy
Lasers
Staining and Labeling
Hypertension

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Distortion of axonal cytoskeleton : An early sign of glaucomatous damage. / Huang, XiangRun; Kong, Wei; Zhou, Ye; Gregori, Giovanni.

In: Investigative Ophthalmology and Visual Science, Vol. 52, No. 6, 01.05.2011, p. 2879-2888.

Research output: Contribution to journalArticle

@article{728524c2b8e5406c92ec1e93d0998d0a,
title = "Distortion of axonal cytoskeleton: An early sign of glaucomatous damage",
abstract = "PURPOSE. Glaucoma damages the retinal nerve fiber layer (RNFL). The purpose of this study was to investigate the distribution of major cytoskeleton components, F-actin, microtubules (MTs), and neurofilaments (NFs), in the RNFL during the development of glaucoma. METHODS. Intraocular hypertension was induced in a rat model by laser photocoagulation of the trabecular meshwork. Retinas were obtained after 2 to 3.5 weeks of treatment. Multiple fluorescent stains were used to identify F-actin, MTs, NFs, and nuclei simultaneously in the same tissue. Distribution of these components in a whole-mounted retina was examined by confocal microscopy. Fluorescent stain was quantitatively described. RESULTS. In normal RNFL F-actin, MTs, and NFs were intensely stained. Along the bundles, F-actin and MTs were strongly colocalized, but alternating strands of F-actin and NFs were apparent. Normal RNFL lacked nuclei. In glaucomatous retinas, irregular staining of F-actin, MTs, and NFs was found within the bundles. A strong network of F-actin appeared on the RNFL surface and between the bundles. In severely damaged retinal regions total loss of F-actin and MTs was found, whereas residual strands of NFs were evident. Before the decrease in RNFL thickness, irregularity of F-actin stain and density of nuclei in the RNFL significantly increased. CONCLUSIONS. The results suggest that F-actin, MTs, and NFs are rich and approximately uniformly distributed in the normal RNFL. Glaucoma causes alteration of the cytoskeleton in the RNFL. F-actin is the most sensitive component in its response to stress on the retina. An increase in the number of nuclei in the RNFL may be an early sign of glaucomatous damage.",
author = "XiangRun Huang and Wei Kong and Ye Zhou and Giovanni Gregori",
year = "2011",
month = "5",
day = "1",
doi = "10.1167/iovs.10-5929",
language = "English",
volume = "52",
pages = "2879--2888",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "6",

}

TY - JOUR

T1 - Distortion of axonal cytoskeleton

T2 - An early sign of glaucomatous damage

AU - Huang, XiangRun

AU - Kong, Wei

AU - Zhou, Ye

AU - Gregori, Giovanni

PY - 2011/5/1

Y1 - 2011/5/1

N2 - PURPOSE. Glaucoma damages the retinal nerve fiber layer (RNFL). The purpose of this study was to investigate the distribution of major cytoskeleton components, F-actin, microtubules (MTs), and neurofilaments (NFs), in the RNFL during the development of glaucoma. METHODS. Intraocular hypertension was induced in a rat model by laser photocoagulation of the trabecular meshwork. Retinas were obtained after 2 to 3.5 weeks of treatment. Multiple fluorescent stains were used to identify F-actin, MTs, NFs, and nuclei simultaneously in the same tissue. Distribution of these components in a whole-mounted retina was examined by confocal microscopy. Fluorescent stain was quantitatively described. RESULTS. In normal RNFL F-actin, MTs, and NFs were intensely stained. Along the bundles, F-actin and MTs were strongly colocalized, but alternating strands of F-actin and NFs were apparent. Normal RNFL lacked nuclei. In glaucomatous retinas, irregular staining of F-actin, MTs, and NFs was found within the bundles. A strong network of F-actin appeared on the RNFL surface and between the bundles. In severely damaged retinal regions total loss of F-actin and MTs was found, whereas residual strands of NFs were evident. Before the decrease in RNFL thickness, irregularity of F-actin stain and density of nuclei in the RNFL significantly increased. CONCLUSIONS. The results suggest that F-actin, MTs, and NFs are rich and approximately uniformly distributed in the normal RNFL. Glaucoma causes alteration of the cytoskeleton in the RNFL. F-actin is the most sensitive component in its response to stress on the retina. An increase in the number of nuclei in the RNFL may be an early sign of glaucomatous damage.

AB - PURPOSE. Glaucoma damages the retinal nerve fiber layer (RNFL). The purpose of this study was to investigate the distribution of major cytoskeleton components, F-actin, microtubules (MTs), and neurofilaments (NFs), in the RNFL during the development of glaucoma. METHODS. Intraocular hypertension was induced in a rat model by laser photocoagulation of the trabecular meshwork. Retinas were obtained after 2 to 3.5 weeks of treatment. Multiple fluorescent stains were used to identify F-actin, MTs, NFs, and nuclei simultaneously in the same tissue. Distribution of these components in a whole-mounted retina was examined by confocal microscopy. Fluorescent stain was quantitatively described. RESULTS. In normal RNFL F-actin, MTs, and NFs were intensely stained. Along the bundles, F-actin and MTs were strongly colocalized, but alternating strands of F-actin and NFs were apparent. Normal RNFL lacked nuclei. In glaucomatous retinas, irregular staining of F-actin, MTs, and NFs was found within the bundles. A strong network of F-actin appeared on the RNFL surface and between the bundles. In severely damaged retinal regions total loss of F-actin and MTs was found, whereas residual strands of NFs were evident. Before the decrease in RNFL thickness, irregularity of F-actin stain and density of nuclei in the RNFL significantly increased. CONCLUSIONS. The results suggest that F-actin, MTs, and NFs are rich and approximately uniformly distributed in the normal RNFL. Glaucoma causes alteration of the cytoskeleton in the RNFL. F-actin is the most sensitive component in its response to stress on the retina. An increase in the number of nuclei in the RNFL may be an early sign of glaucomatous damage.

UR - http://www.scopus.com/inward/record.url?scp=79955947169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955947169&partnerID=8YFLogxK

U2 - 10.1167/iovs.10-5929

DO - 10.1167/iovs.10-5929

M3 - Article

C2 - 21245391

AN - SCOPUS:79955947169

VL - 52

SP - 2879

EP - 2888

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 6

ER -