elastin and Optic-Nerve-Diseases

To analyze the vasculature and extracellular matrix changes in the prelaminar region (PreLR) of the optic nerve head (ONH) and in the peripapillary sclera of eyes with primary open-angle glaucoma (POAG) and age-matched control eyes.. In histologic sagittal sections of 46 eyes with POAG and 45 control eyes (donor ages, 20-96 years), the peripapillary sclera and penetrating vessels were investigated ultrastructurally and with antibodies against elastin, podocalyxin, and α-actin. Within the PreLR, the number and density of capillaries and the thickness of their connective tissue sheaths (CTSs) were quantified. The composition of the CTS was analyzed by using antibodies against collagen types I, III, IV, and VI, and elastin. Areas within the PreLR containing capillaries with thick or thin CTSs were determined.. There were no glaucomatous changes in the peripapillary elastic fibers and in the arterial capillaries in the periphery of the PreLR. In the center of the PreLR, the capillaries gained a CTS that was significantly thicker in POAG eyes than in control eyes, and the area containing capillaries with thick CTSs was significantly larger. These data did not correlate with axon counts.. Lack of glaucomatous changes in elastic fibers of the scleral suspension of the ONH seems to prevent occlusion of penetrating vessels. In the PreLR, thickening of the capillary CTS and enlargement of the area containing capillaries with thickened CTS could increase diffusion time and may impair nutrition of the neuronal tissue.

Topics: Actins; Adult; Aged; Aged, 80 and over; Arterioles; Capillaries; Ciliary Arteries; Connective Tissue; Elastic Tissue; Elastin; Extracellular Matrix; Female; Fluorescent Antibody Technique, Indirect; Glaucoma, Open-Angle; Humans; Male; Microscopy, Fluorescence; Middle Aged; Optic Disk; Optic Nerve Diseases; Sclera; Sialoglycoproteins; Young Adult

Elastin is a major component of the extracellular matrix (ECM) of the lamina cribrosa in the optic nerve head in humans and nonhuman primates. The lamina cribrosa appears to be the site of damage to the retinal ganglion cell axons in glaucomatous optic neuropathy, characterized in many patients by elevated intraocular pressure (IOP). Type 1B astrocytes are the major cell type in the lamina, synthesize elastic fibers during development, express increased elastin mRNA, and synthesize abnormal elastin in glaucoma. In this study, we determined the effect of elevated hydrostatic pressure on the synthesis of elastin by type 1B astrocytes in culture. Type 1B astrocytes were exposed to gradients of hydrostatic pressure and tested for proliferation, morphology, synthesis, and deposition of elastin. Trichloroacetic acid (TCA) and immunoprecipitation of radiolabeled protein determined total new protein and elastin synthesis. Proteins from the conditioned media were analyzed by Western blot. Levels of elastin mRNA were determined by in situ hybridization. Cell proliferation increased approximately 2-fold after exposure to pressure for one day, approximately 5-fold after 3 and 5 days of exposure to pressure. Confocal and electron microscopic cytochemistry showed a marked increase in intracellular elastin in astrocytes exposed to pressure, as compared with controls. Intracellular elastin was associated with the RER-Golgi region and with the cytoskeleton. Total protein and elastin synthesis increased significantly (P < 0.05) at 3- and 5-day exposure to pressure, as well as the level of elastin mRNA. Elastin protein in the media increased with the level of pressure. These results indicate that hydrostatic pressure stimulates type 1B astrocytes to synthesize and secrete soluble elastin into the media. In glaucoma, type 1B astrocytes may respond to IOP-related stress with increased expression of elastin and formation of elastotic fibers leading to loss of elasticity and tissue remodeling.

Topics: Adolescent; Adult; Astrocytes; Cell Division; Cell Size; Cells, Cultured; Child; Culture Media, Conditioned; Elastin; Extracellular Matrix; Glaucoma, Open-Angle; Glial Fibrillary Acidic Protein; Humans; Hydrostatic Pressure; Middle Aged; Optic Disk; Optic Nerve Diseases; RNA, Messenger; Stress, Mechanical

The purpose of this study was to determine whether elastotic degeneration of the elastin component of the lamina cribrosa occurs in optic neuropathy associated with different types of glaucoma. Human optic nerve heads with primary open-angle, neovascular, chronic angle closure and pseudoexfoliation glaucoma, and with varying duration of disease were compared with age-matched normal eyes, using electron microscopy and immunogold labeling of elastin. The percent area occupied by immunogold-labeled elastin material was determined using a digital image analysis system. In all eyes with a history of glaucoma, elastosis was found in the lamina cribrosa and there was a significantly greater percentage of area occupied by elastin compared with age-matched control eyes (P<0.0001). Among the glaucomatous eyes, pseudoexfoliation glaucoma had the largest area of elastosis, followed by primary open-angle and secondary glaucoma (neovascular and chronic angle closure). In all glaucoma samples, large, confluent elastin aggregates of irregular and varied shapes (elastosis) were observed in the lamina cribrosa and insertion region. These results demonstrate that glaucomatous optic neuropathy is associated with elastosis of the lamina cribrosa, which may contribute to the changes in compliance of the optic nerve heads of glaucomatous eyes.

Topics: Aged; Aged, 80 and over; Connective Tissue Diseases; Elastic Tissue; Elastin; Female; Glaucoma; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Optic Disk; Optic Nerve Diseases; Sclera