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Comparative Anatomy of the Trabecular Meshwork, the Optic Nerve Head and the Inner Retina in Rodent and Primate Models Used for Glaucoma Research.

ABSTRACT: Glaucoma is a heterogeneous group of ocular disorders with a multi-faceted etiology. Although numerous studies on glaucoma using different animal models have been published, it is unwise to simply generalize the results of one model to all glaucomatous situations because of the differences in the anatomy and morphology of animal eyes in comparison with humans'. In this review, we highlight the differences in the trabecular meshwork (TM) tissue, lamina cribrosa (LC) region, optic nerve head (ONH) and the inner layer of the retina in mice, rats and monkeys. In comparison with humans, non-human primates show TM, retina and ONH that are anatomically almost identical. The rat model shows many similarities in the aqueous outflow pathway compared to humans. The mouse ONH lacks collagenous LC, and this finding is observed across different mouse strains. The tissue structure of the ONH in rodents is similar to that in humans, although the blood supply shows differences. The number of cells in the ganglion layer depends on the rodent strain. Despite some differences from humans, rodents are a good choice for studying different types of glaucoma, and the modeling method should be selected based on the experimental needs and the hypothesis being tested.

SUBMITTER: Chen L

PROVIDER: S-EPMC6848998 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundElevated intraocular pressure (IOP) is a major risk factor for the development and progression of primary open angle glaucoma and is due to trabecular meshwork (TM) damage. Here, we investigate the role of an endogenous Toll-like receptor 4 (TLR4) ligand, FN-EDA, in the development of glaucoma utilizing a transgenic mouse strain (B6.EDA+/+) that constitutively expresses only FN containing the EDA isoform.MethodsEyes from C57BL6/J (wild-type), B6.EDA+/+ (constitutively active EDA), B6.EDA-/- (EDA null) mice were processed for electron microscopy and consecutive images of the entire length of the TM and Schlemm's canal (SC) from anterior to posterior were collected and montaged into a single image. ECM accumulation, basement membrane length, and size and number of giant vacuoles were quantified by ImageJ analysis. Tlr4 and Iba1 expression in the TM and ONH cells was conducted using RNAscope in situ hybridization and immunohistochemistry protocols. IOP was measured using a rebound tonometer, ON damage assessed by PPD stain, and RGC loss quantified in RBPMS labeled retina flat mounts.ResultsUltrastructure analyses show the TM of B6.EDA+/+ mice have significantly increased accumulation of ECM between TM beams with few empty spaces compared to C57BL/6 J mice (p < 0.05). SC basement membrane is thicker and more continuous in B6.EDA+/+ mice compared to C57BL/6 J. No significant structural differences are detected in the TM of EDA null mice. Tlr4 and Iba1 expression is increased in the TM of B6.EDA+/+ mice compared to C57BL/6 J eyes (p < 0.05). IOP is significantly higher in B6.EDA+/+ mice compared to C57BL/6 J eyes (p < 0.001), and significant ON damage (p < 0.001) and RGC loss (p < 0.05) detected at 1 year of age. Tlr4 mRNA is expressed in mouse ONH cells, and is present in ganglion cell axons, microglia, and astrocytes. There is a significant increase in the area occupied by Iba-1 positive microglia cells in the ONH of B6.EDA+/+ mice compared to C57BL/6 J control eyes (p < 0.01).ConclusionsB6.EDA+/+ mice have increased ECM accumulation in the TM, elevated IOP, enhanced proinflammatory changes in the ONH, loss of RGCs, and ONH damage. These data suggest B6.EDA+/+ mice recapitulate many aspects of glaucomatous damage.

Dataset Information

Comparative Anatomy of the Trabecular Meshwork, the Optic Nerve Head and the Inner Retina in Rodent and Primate Models Used for Glaucoma Research.

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