Integrins in the optic nerve head: potential roles in glaucomatous optic neuropathy (an American Ophthalmological Society thesis).
OBJECTIVE
To demonstrate that specific distributions of integrin-based focal mechanoreceptors exist in primate optic nerve heads, suitable for translating stress and strain into the cellular responses of glaucomatous optic neuropathy.


METHODS
Normal human (N = 20) and rhesus monkey (N = 14) optic nerve heads and 32 glaucomatous optic nerve heads were processed for immunohistochemistry to determine the structural distribution of integrin subunits alpha1, alpha2, alpha3, alpha4, alpha5, alpha6, alphav, beta1, beta2, beta3, and beta4. Labeling patterns in glaucoma specimens were compared with those of normal eyes.


RESULTS
In all specimens, cells within collagenous laminar beams and sclera failed to label with any integrin antibodies. In normal eyes, alpha2, alpha3, alpha6, beta1, and beta4 antibodies localized to astrocytes along the margins of laminar beams and within glial columns. alpha3, alpha5, alpha6, alphav, beta1, and beta4 labeled vascular endothelial cells. In severely damaged glaucoma specimens, cells anterior to the compressed lamina cribrosa displayed persistent label for alpha2, alpha3, beta1, and beta4, whereas label for alpha4 increased and alpha6 was decreased.


CONCLUSIONS
Integrins alpha2beta1, alpha3beta1, alpha6beta1, and alpha6beta4 may provide attachment for astrocytes to basement membranes via laminin, providing opportunities to sense changes in stress and strain within and anterior to the lamina cribrosa. Vascular endothelial cell stress may be mediated by integrins alpha3beta1, alpha6beta1, and alpha6beta4, along with alpha5beta1 and alphavbeta1. In advanced damage, reduced alpha6 label and variable label for betabeta 4 anterior to the lamina cribrosa suggests astrocyte migration. Increased label for alpha4 subunits suggests activation of microglia.
Morrison
John C
JC
Oregon Health and Science University, Casey Eye Institute, Portland, Oregon, USA.
D000368:Aged; D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005901:Glaucoma / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D039001:Integrin alpha Chains / Q000378:metabolism*; D039641:Integrin beta Chains / Q000378:metabolism*; D008253:Macaca mulatta; D008465:Mechanoreceptors / Q000378:metabolism; D009898:Optic Disk / Q000378:metabolism*; D009901:Optic Nerve Diseases / Q000378:metabolism*
D053674:Aggrecans; D024042:Collagen Type I; D024141:Collagen Type IV; D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D039001:Integrin alpha Chains; D039641:Integrin beta Chains