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W. Kong, X.-R. Huang; Change of Axonal Cytoskeleton in Glaucomatous Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2789.
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© ARVO (1962-2015); The Authors (2016-present)
The retinal nerve fiber layer (RNFL), which consists of axons of retinal ganglion cells, is damaged in glaucoma. Cytoskeletal components of axons are expected to change in the disease. Axonal cytoskeleton is made up of three kinds of protein filaments: microtubules (MTs), actin filaments (F-actin) and neurofilaments (NFs). F-actin and MTs closely coordinate in both functional and structural organization. The purpose of this study was to determine change of F-actin and MTs in retinas with glaucomatous damage.
High intraocular pressure (IOP) was induced unilaterally by laser photocoagulation of trabecular meshwork. Distribution of F-actin around the ONH was studied by confocal imaging of phalloidin labelled F-actin and MTs were evaluated by measuring retardance of the RNFL. First, RNFL retardance was measured by means of imaging polarimetry. The retina was then stained with phalloidin to label F-actin. F-actin distribution in the flat-mounted retina was examined by confocal laser scanning microscopy. Images of retardance measurements and F-actin staining were aligned to compare F-actin and MT distribution of the same bundles across the retina.
In normal retinas, confocal images showed uniform staining of F-actin within bundles. In glaucomatous eyes, distortion of F-actin staining was first found in the dorsal region; the changes started near the ONH and propagated peripherally along bundles. In normal retinas, RNFL retardance varied along a circular path around the ONH. Along bundles retardance increased monotonically toward the ONH (Fig.), suggesting more MTs near the ONH. In glaucomatous retinas, retardance decreased in bundles with F-actin distortion and was near zero in regions with total loss of F-actin.
Elevation of IOP causes non-uniform alteration of both F-actin and MTs across the retina. The degree of F-actin change varies from distortion of F-actin staining to the total disappearance of the structure. MTs decrease in the same region with F-actin alteration. The result suggests interaction of F-actin and MTs accompanies glaucomatous damage.
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