Distinct Role of Lycium barbarum L. Polysaccharides in Oxidative Stress-Related Ocular Diseases

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 215 - 215

Published: Jan. 31, 2023

Oxidative stress is an imbalance between the increased production of reactive species and reduced antioxidant activity, which can cause a variety disturbances including ocular diseases. Lycium barbarum polysaccharides (LBPs) are complex isolated from fruit L. barbarum, showing distinct roles in antioxidants. Moreover, it relatively safe non-toxic. In recent years, activities LBPs have attracted remarkable attention. order to illustrate its significance underlying therapeutic value for vision, we comprehensively review progress on mechanisms LBP potential applications diseases, diabetic retinopathy, hypertensive neuroretinopathy, age-related macular degeneration, retinitis pigmentosa, retinal ischemia/reperfusion injury, glaucoma, dry eye syndrome, cataract.

Language: Английский

---

The Influence of Mitochondrial Dynamics and Function on Retinal Ganglion Cell Susceptibility in Optic Nerve Disease

Cells, Journal Year: 2021, Volume and Issue: 10(7), P. 1593 - 1593

Published: June 25, 2021

The important roles of mitochondrial function and dysfunction in the process neurodegeneration are widely acknowledged. Retinal ganglion cells (RGCs) appear to be a highly vulnerable neuronal cell type central nervous system with respect but actual reasons for this still incompletely understood. These have unique circumstance where unmyelinated axons must bend nearly 90° exit eye then cross translaminar pressure gradient before becoming myelinated optic nerve. This region, nerve head, contains some highest density mitochondria present these cells. Glaucoma represents perfect storm events occurring at location, combination changes reassignment metabolic support functions supporting glia, which appears apply increased stress RGC leading failure axonal transport mechanisms. However, RGCs themselves also extremely sensitive genetic mutations, particularly genes affecting dynamics clearance. systemically affect every cell, often lead an neuropathy as sole pathologic defect affected patients. review summarizes knowledge structure function, known energy demands neurons general, places context normal pathological characteristics attributed RGCs.

Language: Английский

---

Bax Contributes to Retinal Ganglion Cell Dendritic Degeneration During Glaucoma

Molecular Neurobiology, Journal Year: 2022, Volume and Issue: 59(3), P. 1366 - 1380

Published: Jan. 5, 2022

The BCL-2 (B-cell lymphoma-2) family of proteins contributes to mitochondrial-based apoptosis in models neurodegeneration, including glaucomatous optic neuropathy (glaucoma), which degrades the retinal ganglion cell (RGC) axonal projection visual brain. Glaucoma is commonly associated with increased sensitivity intraocular pressure (IOP) and involves a proximal program that leads RGC dendritic pruning distal underlies axonopathy projection. While genetic deletion Bcl2-associated X protein (Bax-/-) prolongs body survival glaucoma nerve trauma, persists, thus raising question whether dendrites light response are protected. Here, we used an inducible model Bax-/- mice determine if Bax degeneration. We performed whole-cell recordings dye filling RGCs signaling onset (αON-Sustained) offset (αOFF-Sustained). recovered morphologies by confocal microscopy analyzed arbor complexity size. Additionally, assessed axon function measuring anterograde transport cholera toxin subunit B superior colliculus behavioral spatial frequency threshold (i.e., acuity). found 1 month IOP elevation did not cause significant death either WT or retinas. However, reduced αON-Sustained αOFF-Sustained RGCs. In absence Bax, αON- arbors remained intact following elevation. addition dendrites, neuroprotection generalized αON-and light- current-evoked responses. Both acuity declined during mice. Collectively, our results indicate degeneration distinguishes neurodegenerative programs involved progression glaucoma.

Language: Английский

---

Signalling pathways and cell death mechanisms in glaucoma: Insights into the molecular pathophysiology

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 94, P. 101216 - 101216

Published: Oct. 17, 2023

Glaucoma is a complex multifactorial eye disease manifesting in retinal ganglion cell (RGC) death and optic nerve degeneration, ultimately causing irreversible vision loss. Research recent years has significantly enhanced our understanding of RGC degenerative mechanisms glaucoma. It evident that high intraocular pressure (IOP) not the only contributing factor to glaucoma pathogenesis. The equilibrium pro-survival pro-death signalling pathways retina strongly influences function survival RGCs axons Molecular evidence from human tissue analysis range experimental models have contributed unravelling these mechanisms. Accumulating reveals wide molecular can operate -either alone or via intricate networks - induce neurodegeneration. roles several molecules, including neurotrophins, interplay intracellular kinases phosphates, caveolae adapter proteins, serine proteases their inhibitors, nuclear receptors, amyloid beta tau, how dysfunction affects neurons are discussed this review. We further underscore anatomical alterations various animal exhibiting degeneration susceptibility glaucoma-related neuronal damage helped characterise In addition, we also present different regulated play critical role

Language: Английский

---

Retinal astrocyte morphology predicts integration of vascular and neuronal architecture

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Aug. 9, 2023

Astrocytes are important regulators of blood flow and play a key role in the response to injury disease central nervous system (CNS). Despite having an understanding that structural changes these cells have consequences for local neurovascular physiology, individual astrocyte morphology remains largely unexplored retina. Here, we used MORF3 mice capture full membranous over fifteen hundred astrocytes mouse retina, highly metabolically active component CNS. We demonstrate retinal been misrepresented as stellate due marker use like GFAP S100β which underestimates cell complexity. also find contain recurring morphological motifs predictive underlying architecture inner retina suggestive function. These predict fine sampling integration ganglion electrical activity with regulation. Additionally, our data shows participate interactions much greater degree than currently reported. 100% contact vasculature through one three mutually exclusive classes connections. Similarly, some neuronal element, be it RGC axon or soma. Finally, report depends on eccentricity, appearing compressed near nerve head periphery. results reveal large complexity informs their contribution coupling

Language: Английский

---

Utilizing extracellular vesicles as a drug delivery system in glaucoma and RGC degeneration

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 372, P. 209 - 220

Published: June 22, 2024

Retinal diseases are the leading cause of blindness, resulting in irreversible degeneration and death retinal neurons. One such cell type, ganglion (RGC), is responsible for connecting retina to rest brain through its axons that make up optic nerve primary lost glaucoma traumatic neuropathy. To date, different therapeutic strategies have been investigated protect RGCs from preserve vision, yet currently available restricted treating neuron loss by reducing intraocular pressure. A major barrier identified these studies drug delivery RGCs, which large part due stability, short duration time at target, low efficiency, undesired off-target effects. Therefore, a system deal with problems needed ensure maximum benefit candidate material. Extracellular vesicles (EV), nanocarriers released all cells, lipid membranes encapsulating RNAs, proteins, lipids. As they naturally shuttle encapsulated compounds between cells communicative purposes, may be exploitable offer opportunities overcome hurdles delivery, including molecular weight, barriers retina, adverse Here, we summarize potential an EV system, discussing their superiorities application target RGCs.

Language: Английский

---

Self‐Assembly Hypoxic and ROS Dual Response Nano Prodrug as a New Therapeutic Approach for Glaucoma Treatments

Advanced Science, Journal Year: 2024, Volume and Issue: 11(41)

Published: Sept. 4, 2024

Abstract Glaucoma is an irreversible blinding eye disease characterized by retinal ganglion cell (RGC) death.Previous studies have demonstrated that protecting mitochondria and activating the CaMKII/CREB signaling pathway can effectively protect RGC axon. However, currently treatments are often unsatisfactory, pathogenesis of glaucoma requires further elucidation. In this study, a ROS‐responsive dual drug conjugate (OLN monomer) first designed simultaneously bonds nicotinamide oleic acid. The self‐assembled into nanoparticles (uhOLN‐NPs) through aggregation multiple micelles possesses ROS scavenging capability. Then, polymer with hypoxic response function designed, which encapsulates uhOLN‐NPs to form responses (HOLN‐NPs). Under hypoxia in RGCs, azo bond HOLN‐NPs breaks releases uhOLN‐NPs. Meanwhile, under high conditions, thioketone broke, leading dissociation nano‐prodrug. released acid co‐scavenge activate pathway, RGCs. exhibit significantly superior protective effect on R28 cells glutamate models glaucoma. accumulation RGCs lead significant inhibition apoptosis axonal damage vivo. Notably, provide new therapeutic approach for patients neurodegenerative disease.

Language: Английский

---

Biodistribution of intravitreal lenadogene nolparvovec gene therapy in nonhuman primates

Molecular Therapy — Methods & Clinical Development, Journal Year: 2021, Volume and Issue: 23, P. 307 - 318

Published: Oct. 1, 2021

Lenadogene nolparvovec (Lumevoq) gene therapy was developed to treat Leber hereditary optic neuropathy (LHON) caused by the m.11778G > A in MT-ND4 that affects complex I of mitochondrial respiratory chain. is a replication-defective, single-stranded DNA recombinant adeno-associated virus vector 2 serotype 2, containing codon-optimized complementary encoding human wild-type subunit protein. administered unilateral intravitreal injection LHON patients two randomized, double-masked, and sham-controlled phase III clinical trials (REVERSE RESCUE), resulting bilateral improvement visual acuity. These other earlier results suggest lenadogene may travel from treated untreated eye. To investigate this possibility further, unilaterally injected into vitreous body right eye healthy, nonhuman primates. Viral quantifiable all nerve tissues detected at lower levels some contralateral, noninjected eye, projections, 3 6 months after injection. The transfers thus providing potential explanation for function observed patients.

Language: Английский

---

Retinal ganglion cells adapt to ionic stress in experimental glaucoma

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 27, 2023

Identification of early adaptive and maladaptive neuronal stress responses is an important step in developing targeted neuroprotective therapies for degenerative disease. In glaucoma, retinal ganglion cells (RGCs) their axons undergo progressive degeneration resulting from driven by sensitivity to intraocular pressure (IOP). Despite that can effectively manage IOP many patients progress vision loss, necessitating development neuronal-based therapies. Evidence experimental models glaucoma indicates the disease RGCs experience altered excitability are challenged with dysregulated potassium (K+) homeostasis. Previously we demonstrated certain RGC types have distinct profiles thresholds depolarization block, which associated extracellular K+. Here, used our inducible mouse model investigate how K+ changes exposure elevated IOP. controls, conditions increased enhanced membrane depolarization, reduced action potential generation, widened potentials. Consistent previous work, 4 weeks elevation diminished light-and current-evoked responses. Compared found effects on block threshold, IOP-exposed maintaining greater excitability. Finally, did not alter axon initial segment dimensions, suggesting structural plasticity alone cannot explain decreased sensitivity. Thus, response prolonged process reduces while diminishing These experiments give insight into lay groundwork mechanistic investigation targets therapy.

Language: Английский

---

Metabolic dysregulation in glaucoma

Clinical and Experimental Optometry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 7

Published: Feb. 12, 2025

Glaucoma is a multifactorial neurodegenerative disorder characterised by the progressive loss of retinal ganglion cells, ultimately leading to irreversible blindness worldwide. Recent research highlights metabolic dysregulation as crucial factor in pathophysiology glaucoma. This review examines intricate relationship between processes and glaucoma, with focus on key mechanisms such mitochondrial dysfunction, lipid metabolism, glucose roles specific metabolites. Mitochondrial dysfunction commonly observed impaired energy production that compromises cellular viability. Alterations including changes fatty acid profiles peroxidation, contribute injury apoptosis cells. Moreover, disturbances reduced glycolytic activity, affect availability neurotrophic support are vital for cells survival. The also explores metabolites, lactate glutamate, context health, how their may exacerbate glaucomatous damage. Additionally, interplay elevated intraocular pressure analysed, particularly regard its impact ocular blood flow health. Understanding these essential identifying potential therapeutic strategies. By deepening our understanding foundations new avenues effective treatments arise, addressing nature this complex disease improving patient outcomes.

Language: Английский

---