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
Y1 - 2011/5
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.
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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 -