Abstract
Primary Open-Angle Glaucoma (POAG) is a neurodegenerative disease, and its clinical outcomes lead to visual field constriction and blindness. POAG’s etiology is very complex and its pathogenesis is mainly explained through both mechanical and vascular theories. The trabecular meshwork (TM), the most sensitive tissue of the eye anterior segment to oxidative stress (OS), is the main tissue involved in early-stage POAG, characterized by an increase in pressure. Preclinical assessments of neuroprotective drugs on animal models have not always shown correspondence with human clinical studies. In addition, intra-ocular pressure management after a glaucoma diagnosis does not always prevent blindness. Recently, we have been developing an innovative in vitro 3Dadvanced human trabecular cell model on a millifluidicplatform as a tool to improve glaucoma studies. Herein, we analyze the effects of prolonged increased pressure alone and, in association with OS, on such in vitro platform. Moreover, we verify whethersuch damaged TM triggers apoptosis on neuron-like cells. The preliminary results show that TM cells are less sensitive to pressure elevation than OS, and OS-damaging effects were worsened by the pressure increase. The stressed TM releases harmful signals, which increase apoptosis stimuli on neuron-like cells, suggesting its pivotal role in the glaucoma cascade.
Highlights
Glaucoma comprises a group of progressive neurodegenerative eye diseases characterized by a selective loss of retinal ganglion cells (RGCs) and their axons, the cupping of the optic nerve head, as well as the loss of vision [1,2].Primary open-angle glaucoma (POAG), the most common form of glaucoma, is anatomically characterized by an open-iridocorneal angle, as well as by an increase in the intraocular pressure (IOP) [3]
The neuronal phenotype of retinoic acid (RA)-SH-SY5Ycells was further confirmed by labeling cells with an antibody for neuron-specific βIII tubulin, which is considered a marker of neurogenesis, axon guidance and maintenance
This study reports a novel in vitro approach used to deepen the knowledge of both trabecular meshwork (TM)
Summary
70%), is anatomically characterized by an open-iridocorneal angle, as well as (but not always) by an increase in the intraocular pressure (IOP) [3]. In HTG, both the progressive morphofunctional decay of trabecular meshwork (TM) (e.g., TM stiffening) and the reduction in its cell number are responsible for IOP elevation [5,6], it is reasonable to ask whether such changes are responsible for the molecular signals thatare capable of triggering RGC apoptosis [7]. Glaucoma therapy is mainly focused on lowering the IOP, with the aim ofslowing down disease progression. This therapeutic approach, in some cases, does not necessarily stop RGC loss, and can still lead to progressive blindness [1,8]. The explanation for why lowering the IOP does not always provide a satisfactory outcome may well be related to a variety of molecular signals involved in glaucoma pathogenesis, including oxidative stress, mitochondrial damage, apoptotic signals arising from different ocular areas, glutamate excitotoxicity, pro-inflammatory cytokines and the disruption of the integrity of the blood–retinal barrier [9,10]
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