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Abstract #116977 Published in IGR 24-4
IOP and glaucoma damage: The essential role of optic nerve head and retinal mechanosensors
Pitha I; Du L; Nguyen TD; Quigley HProgress in Retinal and Eye Research 2024; 99: 101232
There are many unanswered questions on the relation of intraocular pressure to glaucoma development and progression. IOP itself cannot be distilled to a single, unifying value, because IOP level varies over time, differs depending on ocular location, and can be affected by method of measurement. Ultimately, IOP level creates mechanical strain that affects axonal function at the optic nerve head which causes local extracellular matrix remodeling and retinal ganglion cell death - hallmarks of glaucoma and the cause of glaucomatous vision loss. Extracellular tissue strain at the ONH and lamina cribrosa is regionally variable and differs in magnitude and location between healthy and glaucomatous eyes. The ultimate targets of IOP-induced tissue strain in glaucoma are retinal ganglion cell axons at the optic nerve head and the cells that support axonal function (astrocytes, the neurovascular unit, microglia, and fibroblasts). These cells sense tissue strain through a series of signals that originate at the cell membrane and alter cytoskeletal organization, migration, differentiation, gene transcription, and proliferation. The proteins that translate mechanical stimuli into molecular signals act as band-pass filters - sensing some stimuli while ignoring others - and cellular responses to stimuli can differ based on cell type and differentiation state. Therefore, to fully understand the IOP signals that are relevant to glaucoma, it is necessary to understand the ultimate cellular targets of IOP-induced mechanical stimuli and their ability to sense, ignore, and translate these signals into cellular actions.
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Nanomedicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Glaucoma Center of Excellence, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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