Experimental Eye Research

Retinal diseases remain among the leading causes of visual impairment in developed countries, despite great efforts in prevention and early intervention. Due to the limited efficacy of current retinal therapies, novel therapeutic methods are urgently required. Over the past two decades, advances in next-generation sequencing technology have facilitated research on RNA modifications, which can elucidate the relevance of epigenetic mechanisms to disease. N6-methyladenosine (m6A), formed by methylation of adenosine at the N6-position, is the most widely studied RNA modification and plays an important role in RNA metabolism...

Age-related macular degeneration (AMD) is a leading blinding disease worldwide, and macular neovascularization (MNV) is a common complication encountered in the advanced stages of AMD. While the underlying causes of MNV remain elusive, aberrant multiplication of choroidal endothelial cells (CECs) and increased vascular endothelial growth factor (VEGF) are thought to play significant roles in the occurrence and development of MNV. Allograft inflammatory factor-1(AIF-1) is a crucial regulatory factor of vascular tubular structure formation and growth, involving the proliferation and migration of vascular endothelial cells and various tumor cells...

Diabetic keratopathy (DK) is a common ocular complication of diabetes in which the dendritic cells (DCs)-mediated inflammatory response plays an important role. Nerve growth factor (NGF)/Tropomyosin receptor kinase A (TrkA)-mediated inhibition of the nuclear factor kappa B (NF-κB) pathway can reduce inflammatory cytokine production. Extracellular vesicles (EVs) derived from mouse adipose-derived mesenchymal stem cells (mADSC-EVs) have been explored extensively as treatments for degenerative eye disease...

The vesicant sulfur mustard (SM) is a chemical warfare agent that causes acute and chronic injury to the cornea and proximal anterior segment structures. Despite clinical evidence of SM-exposure causing unexplained retinal deficits, there have been no animal studies conducted to examine the retinal toxicity of this vesciant. The cardinal hallmark of retinal response to stressors or injury is the activation of reactive gliosis, a cellular process largely governed by Müller glia. Previously we showed that corneal exposure to sodium hydroxide elicits rapid induction of reactive gliosis and results in retinal degeneration in a dose-related manner...

Depressed patients who medicate with selective serotonin reuptake inhibitors (SSRIs) often report ocular dryness. Epidemiological studies have found that serotonin and norepinephrine reuptake inhibitors (SNRIs) are not risk factors for dry eye in depressed patients. However, the effect of SNRIs on the ocular surface is unknown. A depression rat model was induced by chronic unpredictable mild stress (CUMS), and SNRIs or SSRIs were administered to the rats for 3 or 6 weeks. The levels of norepinephrine (NE) and serotonin in tear fluid were tested by ELISA...

The mechanical and physical properties of the cornea originate from the microstructure and composition of its extracellular matrix. It is known that collagen fibrils, with a relatively uniform diameter, are organized in a pseudo-hexagonal array. It has been suggested that proteoglycans and the interaction of their glycosaminoglycan (GAG) side chains with themselves and collagen fibrils are important for collagen fibril organization inside the cornea. There are several diseases such as keratoconus in which the regular collagen fibrillar packing becomes distorted causing corneal optical and mechanical properties to be compromised...

Transcorneal electrical stimulation (TES) is used as therapy for retinal diseases such as retinitis pigmentosa (RP) and was suggested for assessing retinal sensitivity by determining phosphene thresholds, subjective luminance impressions caused by retinal stimulation. Further applications concerned the accommodation process, revealing an improved accommodative amplitude in presbyopic eyes after TES treatment. The respective changes of the ciliary muscle (CM), the structure most important for near vision, during TES are yet unknown...

N6 -methyladenosine (m6 A) modification is one of the most common types of methylation modifications in eukaryotic mRNA. However, its role in the pathogenesis of pseudoexfoliation glaucoma (PXG) has not yet been reported. To enhance understanding in this regard, we assessed the m6 A methylome in the aqueous humor of patients with PXG. MeRIP-Seq and RNA-Seq analyses were performed to compare the m6 A methylomes and gene expression profiles of the aqueous humor of patients with PXG with those of patients with age-related cataract (ARC)...

Meibomian glands (MGs) are vital for ocular surface health. However, the roles of inflammation in the progression of meibomian gland dysfunction (MGD) are largely unknown. In this study, the roles of the inflammation factor interleukin-1β (IL-1β) via the p38 mitogen-activated protein kinases (MAPK) signaling pathway on rat meibomian gland epithelial cells (RMGECs) were explored. Eyelids from adult rat mice at 2 months and 2 years of age were stained with specific antibodies against IL-1β to identify inflammation levels...

Corneal alkali burn (AB) is a blindness-causing ocular trauma commonly seen in clinics. An excessive inflammatory reaction and stromal collagen degradation contribute to corneal pathological damage. Luteolin (LUT) has been studied for its anti-inflammatory effects. In this study, the effect of LUT on cornea stromal collagen degradation and inflammatory damage in rats with corneal alkali burn was investigated. After corneal alkali burn, rats were randomly assigned to the AB group and AB + LUT group and received an injection of saline and LUT (200 mg/kg) once daily...

Posterior capsule opacification (PCO) is a serious complication after cataract surgery. Diabetes could increase the occurrence of PCO, but the mechanism is still unclear. The purpose of this study is to investigate the role of small extracellular vesicles (sEVs) derived from diabetic aqueous humor in PCO process. Intraoperatively-derived aqueous humor sEVs from patients with diabetic related cataract (DRC) promoted the epithelial-mesenchymal transition (EMT) and metastasis of human lens epithelial cells (LECs)...

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of severe vision loss in industrialized nations. Important factors in pathogenesis are oxidative stress, inflammation, and, in the wet form of AMD, angiogenesis. Fucoidans, sulfated polysaccharides from brown algae, may have antioxidant, anti-inflammatory, and antiangiogenic effects. In this study, we established specific gene expression panels for inflammation, oxidative stress and angiogenesis in porcine retinal pigment epithelium (RPE), and investigated the effect of fucoidans on gene expression under different noxious agents...

We aimed to explore the effect of dibazol on the ophthalmic artery (OA) and ophthalmic artery smooth muscle cells (OASMCs) of C57BL/6J mice as well as the underlying mechanisms. The OA of C57BL/6J mice was isolated under a dissecting microscope for primary OASMCs culture and myogenic tests. OASMCs were identified through morphological and immunofluorescence analyses. Morphology changes in the OASMCs were examined by staining using rhodamine-phalloidin. We performed a collagen gel contraction assay to measure the contractile and relaxant activities of the OASMCs...

The polymer coated polymeric (PCP) microneedles (MNs) is a novel approach for controlled delivery of drugs (without allowing release of the excipients) to the target site. PCP MNs was explored as an approach to deliver the drug intravitreally to minimize the risks associated with conventional intravitreal injections. The core MNs was fabricated with polyvinyl pyrrolidone K30 (PVP K30) and coating was with Eudragit E100. Preformulation studies revealed that the films prepared using Eudragit E 100 exhibited excellent integrity in the physiological medium after prolonged exposure...

Vitreomacular traction syndrome results from persistent vitreoretinal adhesions in the setting of partial posterior vitreous detachment (PVD). Vitrectomy and reattachment of retina is an effective therapeutic approach. The adhesion between vitreous cortex and internal limiting membrane (ILM) of the retina is stronger in youth, which brings difficulties to induce PVD in vitrectomy. Several clinical investigations demonstrated that intravitreous injection of plasmin before vitrectomy could reduce the risk of detachment...

Sulfur mustard (SM) is a chemical warfare agent (CWA) that causes severe eye pain, photophobia, excessive lacrimation, corneal and ocular surface defects, and blindness. However, SM's effects on retinal cells are relatively meager. This study investigated the role of SM toxicity on Müller glial cells responsible for cellular architecture, inner blood-retinal barrier maintenance, neurotransmitter recycling, neuronal survival, and retinal homeostasis. Müller glial cells (MIO-M1) were exposed to SM analog, nitrogen mustard (NM), at varying concentrations (50-500 μM) for 3 h, 24 h, and 72 h...

Corneal endothelium is mostly sensitive to oxidative pressure and mitochondrial dysfunction. However, the oxidative-antioxidant mechanism of corneal endothelial cells (CECs) remains partially defined. Silent information regulator 1 (SIRT1) is a well-studied therapeutic target of oxidative damage. This study aimed to determine the SIRT1 expression in ultraviolet A (UVA)-induced corneal endothelial damage and explore potential drugs to repair corneal endothelial oxidative injury. In this study, we showed that CECs exhibited cellular apoptosis, reactive oxygen species (ROS) accumulation and decreased SIRT1 expression...

Retinitis pigmentosa (RP) is a group of devastating inherited retinal diseases that leads to visual impairment and oftentimes complete blindness. Currently no cure exists for RP thus research into prolonging vision is imperative. Sigma 1 receptor (Sig1R) is a promising small molecule target that has neuroprotective benefits in retinas of rapidly-degenerating mouse models. It is not clear whether Sig1R activation can provide similar neuroprotective benefits in more slowly-progressing RP models. Here, we examined Sig1R-mediated effects in the slowly-progressing RhoP23H/+ mouse, a model of autosomal dominant RP...

Keratoconus is a progressive disorder of the cornea and is typically considered a noninflammatory disease. However, increasing evidence indicates that immune disorders play an essential role in keratoconus progression, but the immune-related etiology remains elusive. Here, we comprehensively utilized bioinformatics approaches and experimental methods to explore the potential immunoregulatory mechanism of keratoconus progression. Transcriptomics data containing two keratoconus patient groups was derived from the public dataset GSE151631...

Nystagmus is an ocular condition characterized by bilateral involuntary ocular oscillation which can severely affect vision. When not associated with other ocular or systemic diseases, it is referred to as idiopathic or congenital motor nystagmus (CMN). Genome-wide linkage studies have previously identified several loci associated with CMN, however the genes responsible for some of these loci have yet to be identified. We have examined a large, five-generation family with autosomal dominant CMN. Our purpose was to characterize the clinical manifestations and reveal the molecular basis of the disease in this family...