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Lisa A Ostrin, Christine Wildsoet; Guinea pig optic nerve head. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3612.
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The guinea pig is becoming an increasingly popular model of human myopia. The goal of this study was to characterize and compare the optic nerve head (ONH) and sclera of the guinea pig with other animal models of human myopia and glaucoma. Myopia carries an increased risk of glaucoma. The lamina cribrosa (LC) of the ONH has been implicated as a site of axon damage in glaucoma and in many species, is continuous with the sclera. It is plausible that it is also abnormal in myopia.
Pigmented and albino guinea pig eyes (n=18, ages 2-3 months) were enucleated and the ONH and surrounding sclera dissected. After formalin fixation , four eyes were paraffin embedded for hematoxylin and eosin (H&E) staining. Four eyes were cryoprotected and frozen for immunostaining. Primary antibodies included collagen types I-V, elastin, fibronectin and glial fibrillary acidic protein (GFAP). Remaining eyes were fixed in 2% gluteraldehyde. Two ONHs were stained with osmium tetroxide (OsO4) and embedded in resin for transmission electron microscopy (TEM). Eight ONHs underwent alkali maceration with 10% NaOH to remove cellular tissue, before staining with OsO4 and dehydration for scanning electron microscopy (SEM) to evaluate the fiber organization.
H&E-stained sections showed retinal ganglion cell axons organizing into fascicles in the prelaminar and laminar region. Immunostained sections revealed collagen types I, III, IV and V in the ONH, as well as elastin, GFAP and fibronectin. SEM revealed the scleral canal to have a well-defined LC with radially-oriented collagen beams, with spaces between presumably occupied by ganglion cell axons and other support cells in the intact ONH. TEM images confirmed the latter, revealing collagen fibrils surrounding non-myelinated nerve bundles in the LC region, with myelination and decreased collagen posterior to the LC. Adjacent sclera was composed of crimped collagen fibers in a crisscross arrangement. The sclera and LC were qualitatively similar in structure in pigmented and albino guinea pigs.
Unlike mice, another rodent model for myopia and glaucoma, the ONH of guinea pig includes a radially-organized, collagen-based LC, similar to that of the tree shrew, but different from primates in which organization is a porous collagenous meshwork. Nonetheless, the overall structural similarity of the LC suggests that the guinea pig is a suitable model for investigating the relationship between myopia and glaucoma.
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