glaucoma Stem cell

Glaucoma, characterized by a degenerative loss of retinal ganglion cells, is the second leading cause of blindness worldwide. There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury. Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases. In this review, we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture, including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes...

Glaucoma is a neurodegenerative eye disease that causes permanent vision impairment. The main pathological characteristics of glaucoma are retinal ganglion cell (RGC) loss and optic nerve degeneration. Glaucoma can be caused by elevated intraocular pressure (IOP), although some cases are congenital or occur in patients with normal IOP. Current glaucoma treatments rely on medicine and surgery to lower IOP, which only delays disease progression. First-line glaucoma medicines are supported by pharmacotherapy advancements such as Rho kinase inhibitors and innovative drug delivery systems...

Glaucoma is a multifactorial, irreversible blinding eye disease characterized by a large number of retinal ganglion cell (RGC) deaths. Müller cell-derived retinal stem cells (RSCs) can be induced to differentiate into RGCs under certain conditions. This study aimed to explore the regulatory effect and mechanism of TRIM9 on the differentiation of Müller cell-derived stem cells into RGCs. First, episcleral vein cauterization was used to induce high intraocular pressure (IOP) rat model. Next, Müller cells were isolated from rat retina, identified and induced to dedifferentiate into RSCs...

In optic neuropathies, including glaucoma, retinal ganglion cells (RGCs) die. Cell transplantation and endogenous regeneration offer strategies for retinal repair, however, developmental programs required for this to succeed are incompletely understood. To address this, we explored cellular reprogramming with transcription factor (TF) regulators of RGC development which were integrated into human pluripotent stem cells (PSCs) as inducible gene cassettes. When the pioneer factor NEUROG2 was combined with RGC-expressed TFs (ATOH7, ISL1, and POU4F2) some conversion was observed and when pre-patterned by BMP inhibition, RGC-like induced neurons (RGC-iNs) were generated with high efficiency in just under a week...

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation...

The endoplasmic reticulum (ER) functions as a quality-control organelle for protein homeostasis, or "proteostasis". The protein quality control systems involve ER-associated degradation, protein chaperons, and autophagy. ER stress is activated when proteostasis is broken with an accumulation of misfolded and unfolded proteins in the ER. ER stress activates an adaptive unfolded protein response to restore proteostasis by initiating protein kinase R-like ER kinase, activating transcription factor 6, and inositol requiring enzyme 1...

Maintenance of the visual function is the desired outcome of ophthalmologic therapies. The shortcomings of the current treatment options, like partial recovery, post-operation failure, rigorous post-operative care, complications, etc., which are usually encountered with the conventional treatment options has warranted newer treatment options that may eliminate the root cause of diseases and minimize the side effects. Cell therapies, a class of regenerative medicines, have emerged as cutting-edge treatment option...

Research has shown that the therapeutic effect of mesenchymal stem cells (MSCs) is partially due to its secreted factors as opposed to the implantation of the cells into the treated tissue or tissue replacement. MSC secretome, especially in the form of conditioned medium (MSC-CM) is now being explored as an alternative to MSCs transplantation. Despite the observed benefits of MSC-CM, only a few clinical trials have evaluated it and other secretome components in the treatment of eye diseases. This review provides insight into the potential therapeutic use of MSC-CM in eye conditions, such as corneal diseases, dry eye, glaucoma, retinal diseases and uveitis...

The human eye plays a critical role in vision perception, but various retinal degenerative diseases such as retinitis pigmentosa (RP), glaucoma, and age-related macular degeneration (AMD) can lead to vision loss or blindness. Although progress has been made in understanding retinal development and in clinical research, current treatments remain inadequate for curing or reversing these degenerative conditions. Animal models have limited relevance to humans, and obtaining human eye tissue samples is challenging due to ethical and legal considerations...

Retinal degenerative diseases cause blindness characterized by a progressive decline in the number and function of retinal pigment epithelium (RPE), photoreceptor cells, and ganglion cells. Such diseases include retinitis pigmentosa (RP), glaucomatous optic neuropathy, age-related macular degeneration and diabetic optic neuropathy. Recent studies have demonstrated that Müller glial cells (MGCs), an endogenous alternative source of retinal neurons, are important glial cells involved in retinal development, damage, and regeneration, making it an excellent target for retinal nerve regeneration...

BACKGROUND AND OBJECTIVE: Based on basic knowledge and prior research on nitric oxide (NO), the potential of NO for treating eye diseases is reviewed, and the possibility of NO-based eye drops in clinical practice and the future potential of NO in ophthalmology are discussed. METHODS: A PubMed search was performed for English-language original reports and reviews using the following key words: nitric oxide, eye, ocular, and drug. KEY CONTENT AND FINDINGS: NO is synthesized in the human body by NO synthase (NOS) from L-arginine or through enzyme-dependent reduction of dietary nitrate...

AIM: The study aimed to evaluate the differentiation ability of intravitreally injected rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) to retinal ganglion-like cells in a polystyrene microsphere induced rat glaucoma model. MATERIALS AND METHODS: The glaucoma rat model was generated via intracameral injection of 7 microliter polystyrene microspheres. Green fluorescence protein-labeled (GFP) rBM-MSCs were transplanted intravitreally at or after induction of ocular hypertension (OHT), depending on the groups...

Glaucoma, an age-related neurodegenerative disease, is characterized by the death of retinal ganglion cells (RGCs) and the corresponding loss of visual fields. This disease is the leading cause of irreversible blindness worldwide, making early diagnosis and effective treatment paramount. The pathophysiology of primary open-angle glaucoma (POAG), the most common form of the disease, remains poorly understood. Current available treatments, which target elevated intraocular pressure (IOP), are not effective at slowing disease progression in approximately 30% of patients...

Retinal ganglion cells (RGCs) connect the retina with the higher centers in the brain for visual perception. Their degeneration leads to irreversible vision loss in glaucoma patients. Since human RGCs (hRGCs) are born during fetal development and connections with the central targets are established before birth, the mechanism underlying their axon growth and guidance remains poorly understood. Here, using RGCs directly generated from human embryonic stem cells, we demonstrate that hRGCs express a battery of guidance receptors...

Retinal ganglion cells (RGCs) are essential for vision perception. In glaucoma and other optic neuropathies, RGCs and their optic axons undergo degenerative change and cell death; this can result in irreversible vision loss. Here we developed a rapid protocol for directly inducing RGC differentiation from human induced pluripotent stem cells (hiPSCs) by the overexpression of ATOH7, BRN3B, and SOX4. The hiPSC-derived RGC-like cells (iRGCs) show robust expression of various RGC-specific markers by whole transcriptome profiling...

Since the discovery of the mechanosensitive Piezo1 channel in 2010, there has been a significant amount of research conducted to explore its regulatory role in the physiology and pathology of various organ systems. Recently, a growing body of compelling evidence has emerged linking the activity of the mechanosensitive Piezo1 channel to health and disease of the central nervous system. However, the exact mechanisms underlying these associations remain inadequately comprehended. This review systematically summarizes the current research on the mechanosensitive Piezo1 channel and its implications for central nervous system mechanobiology, retrospects the results demonstrating the regulatory role of the mechanosensitive Piezo1 channel on various cell types within the central nervous system, including neural stem cells, neurons, oligodendrocytes, microglia, astrocytes, and brain endothelial cells...

The selective degeneration of retinal ganglion cells (RGCs) is a common feature in glaucoma, a complex group of diseases, leading to irreversible vision loss. Stem cell-based glaucoma disease modeling, cell replacement, and axon regeneration are viable approaches to understand mechanisms underlying glaucomatous degeneration for neuroprotection, ex vivo stem cell therapy, and therapeutic regeneration. These approaches require direct and facile generation of human RGCs (hRGCs) from pluripotent stem cells. Here, we demonstrate a method for rapid generation of hRGCs from banked human pluripotent stem cell-derived retinal progenitor cells (hRPCs) by recapitulating the developmental mechanism...

The trabecular meshwork (TM) of the eye serves as an essential tissue in controlling aqueous humor (AH) outflow and intraocular pressure (IOP) homeostasis. However, dysfunctional TM cells and/or decreased TM cellularity is become a critical pathogenic cause for primary open-angle glaucoma (POAG). Consequently, it is particularly valuable to investigate TM characteristics, which, in turn, facilitates the development of new treatments for POAG. Since 2006, the advancement in induced pluripotent stem cells (iPSCs) provides a new tool to (1) model the TM in vitro and (2) regenerate degenerative TM in POAG...

Glaucomatous optic neuropathy (GON) is the major cause of irreversible visual loss worldwide and can result from a range of disease etiologies. The defining features of GON are retinal ganglion cell (RGC) degeneration and characteristic cupping of the optic nerve head (ONH) due to tissue remodeling, while intraocular pressure remains the only modifiable GON risk factor currently targeted by approved clinical treatment strategies. Efforts to understand the mechanisms that allow species such as the zebrafish to regenerate their retinal cells have greatly increased our understanding of regenerative signaling pathways...

Glaucoma is the leading cause of irreversible blindness worldwide and its most prevalent subtype is primary open angle glaucoma (POAG). One pathological change in POAG is loss of cells in the trabecular meshwork (TM), which is thought to contribute to ocular hypertension and has thus motivated development of cell-based therapies to refunctionalize the TM. TM cell therapy has shown promise in intraocular pressure (IOP) control, but existing cell delivery techniques suffer from poor delivery efficiency. We employed a novel magnetic delivery technique to reduce the unwanted side effects of off-target cell delivery...