RNA-seq transcriptomic profiling of TGF-ß2-exposed human trabecular meshwork explants: Advancing insights beyond conventional cell culture models.

Primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss, is closely linked to increased intraocular pressure (IOP), with the trabecular meshwork (TM) playing a critical role in its regulation. The TM, located at the iridocorneal angle, acts as a sieve, filtering the aqueous humor from the eye into the collecting ducts, thus maintaining proper IOP levels. The transforming growth factor-beta 2 (TGF-ß2) signaling pathway has been implicated in the pathophysiology of primary open-angle glaucoma POAG particularly, in the dysfunction of the TM. This study utilizes human TM explants to closely mimic in vivo conditions, thereby minimizing transcriptional changes that could arise from cell culture enabling an exploration of the transcriptomic impacts of TGF-ß2. Through bulk RNA sequencing and immunohistological analysis, we identified distinct gene expression patterns and morphological changes induced by TGF-ß2 exposure (5 ng/ml for 48 h). Bulk RNA sequencing identified significant upregulation in genes linked to extracellular matrix (ECM) regulation and fibrotic signaling. Immunohistological analysis further elucidated the morphological alterations, including cytoskeletal rearrangements and ECM deposition, providing a visual confirmation of the transcriptomic data. Notably, the enrichment analysis unveils TGF-ß2's influence on both bone morphogenic protein (BMP) and Wnt signaling pathways, suggesting a complex interplay of molecular mechanisms contributing to TM dysfunction in glaucoma. This characterization of the transcriptomic modifications on an explant model of TM obtained under the effect of this profibrotic cytokine involved in glaucoma is crucial in order to develop and test new molecules that can block their signaling pathways.

[Glaucoma surgeries: Long-term results - A review]. / Les principales chirurgies du glaucome : résultats à long terme ­ une revue de la littérature.

The surgical treatment of glaucoma has been and is still based on filtering surgeries, commonly used for about half a century. The safety and efficacy of these techniques have been well described, as it has also been done for cyclophotocoagulation and valves or tubes, indicated in France mostly for refractory glaucoma. Minimally invasive glaucoma surgeries have emerged in recent decades, increasing the number of therapeutic options, and allowing treatment decisions to be as patient-centered as possible. Most of these techniques have now been studied for more than five years. Since glaucoma is a chronic, progressive optic neuropathy, the sustainability of each surgery's results is essential. The amount of available data concerning long-term efficacy and safety of glaucoma surgeries is increasing, so we have decided to describe it through this review of the literature.

One year efficacy and safety of inferior implantation of Xen 45® Gel Stent in refractory glaucoma.

PURPOSE: The goal of this study was to assess the efficacy and safety of inferior implantation of the Xen Gel 45® Stent in a cohort of refractory glaucoma patients who had undergone multiple failed procedures and lacked healthy superior conjunctiva. PATIENTS AND METHODS: We retrospectively included individuals with refractory glaucoma who underwent implantation of a Xen 45® in the inferior quadrants of the conjunctiva. At the 12-month mark, two success criteria were assessed: "Complete" success, defined as an intraocular pressure (IOP)≤21mmHg with a≥20% reduction in IOP without additional IOP-lowering medications, the absence of a requirement for additional filtering surgery, and the absence of chronic hypotony; and "Qualified" success, which consisted of patients meeting the same criteria but requiring glaucoma medications postoperatively. Safety was also monitored throughout the 12-month follow-up. RESULTS: A total of 35 patients who underwent inferior Xen implantation were assessed. After 12months, 20 patients (57.1%) achieved qualified success, with twelve patients (34.3%) attaining complete success. Excluding five patients who underwent additional filtering surgery during follow-up, the mean IOP decreased significantly from 30.73±9.7mmHg to 16.49±7.9mmHg, representing a mean decrease of 14.24±12.13mmHg (46.5%; P<0.0001). The mean number of medications at 12months decreased from 3.43±1.6 to 1.53±1.52 (-55.4%; P<0.0001). The mean number of needlings was 1.29±1.2. Implant exposure was observed in two patients during the first postoperative month. CONCLUSIONS: Inferior placement of Xen appears to be a viable treatment option for patients with refractory glaucoma and a history of multiple failed glaucoma procedures. It demonstrates both significant efficacy and acceptable safety.

[Hyperbaric oxygen therapy and eye disease: Review of the literature]. / Oxygénothérapie hyperbare et maladies oculaires : une revue de la littérature.

Hyperbaric oxygen therapy consists of breathing 100% oxygen continuously or intermittently in a chamber at a pressure equal to or greater than 1.4 absolute atmospheres. Indicated for the emergency treatment of carbon monoxide poisoning and other medical-surgical pathologies such as gas embolism or necrotizing soft-tissue infections, various studies have shown a beneficial effect of hyperbaric oxygen therapy in certain ocular pathologies, notably of microcirculatory origin, such as central retinal artery occlusion or macular edema linked to retinal vein occlusions. In addition, hyperbaric oxygen might represent an alternative treatment for ocular quinine toxicity and might also be useful as an adjuvant to surgery and antibiotics in cases of periorbital necrotizing fasciitis. On the other hand, oxygen in high concentrations has toxic ocular effects due to the production of reactive oxygen derivatives.

[Primary open angle glaucoma and sleep apnea syndrome: A review of the literature]. / Glaucome primitif à angle ouvert et syndrome d'apnée du sommeil : une revue de la littérature.

The relationship between glaucoma and Obstructive Sleep Apnea Syndrome (OSAS) has long been discussed, with conflicting study findings. OSAS appears in the most recent studies to be more of an aggravating factor than an independent risk factor for glaucoma. Patients with OSAS may develop a more rapid progression of primary open-angle glaucoma (POAG). OSAS may damage the optic nerve not only by increasing the intraocular pressure (IOP) but also by altering the blood supply to the optic nerve as shown by more recent work with OCT-Angiography. Although the systemic benefits of Continuous Positive Airway Pressure (CPAP) have been demonstrated, few studies have evaluated its effect on the optic nerve. CPAP might act on glaucomatous neuropathy by improving the blood supply to the optic nerve. The study of this mechanism of action might provide new insights into the relationship between OSAS and glaucoma.

[Biomechanics of the lamina cribrosa: A determining factor in glaucomatous neuropathy. A review of the literature]. / Biomécanique de la lame criblée : un facteur déterminant de la neuropathie glaucomateuse. Une revue de la littérature.

Glaucoma is a chronic optic neuropathy characterized by progressive sclero-laminar remodeling. The main factor at the origin of these deformations is the intraocular pressure (IOP), the effect of which varies according to the biomechanical properties of the individual lamina cribrosa (LC). In this environment, the LC represents a malleable zone of weakness within a rigid corneoscleral shell. It is a dynamic structure whose movements play a key role in the pathogenesis of glaucoma: displacing it posteriorly, in addition to contributing to the characteristic appearance of glaucomatous cupping, would increase constriction on the nerve fibers and the laminar capillaries. Often incorrectly considered permanent in adults, these deformations have a certain degree of reversibility, which is currently better characterized thanks to progress in imaging techniques. The occurrence of anterior displacement and laminar thickening following a reduction in IOP could thus constitute a good prognostic factor by reducing mechanical stress on this region. These changes would tend to reduce laminar pore tortuosity and shear forces, which are probably key mechanisms of axonal loss in glaucoma.

[Role of the lamina cribrosa in the pathogenesis of glaucoma. A review of the literature]. / Rôle de la lame criblée dans la pathogenèse du glaucome. Une revue de la littérature.

Located within the scleral canal, the lamina cribrosa is a sieve-like structure separating the intraocular and retrobulbar portions of the optic nerve. Identified as the main site of axonal damage in glaucomatous optic neuropathy, the study of the lamina cribrosa has been of great interest for many years. Numerous studies have explored the histological and morphological characteristics of the laminar region in healthy subjects as well as glaucoma patients. More recently, the development of adaptive optics systems and new generations of OCT has allowed great progress in the understanding of the pathogenesis of glaucoma and has opened new perspectives for the improvement of diagnostic procedures.