Search Results (173)

The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation remains a standard and effective intervention for severe corneal dysfunction, limitations in donor tissue availability and the risk of immunogenic graft rejection necessitate alternative therapeutic strategies. Furthermore, for cases of isolated epithelial disfunction, a full-thickness cornea graft may not be required or effective. This review examines the potential of corneal epithelial constructs derived from autologous stem cells with functional barrier properties for corneal reconstruction and in vitro pharmacotoxicity testing. In this review, we delineate the current limitations of corneal transplantation, the advantages of stem cell-based approaches, and recent advances in generating engineered corneal epithelium. Finally, we address remaining technical challenges and propose future research directions aimed at clinical translation. Full article

Background: Post-traumatic corneal wounds that require suturing are quite common; they reduce corneal transparency and cause corneal distortion, leading to corneal astigmatism and higher-order aberrations. Excimer laser treatment can be a potentially beneficial intervention for such wounds. The observation aimed to evaluate the effectiveness of topography-guided custom ablation treatment (TCAT) in patients with corneal injuries. Methods: This observation included three patients with corneal penetrating trauma (full-thickness corneal scar) and one patient with corneal blunt trauma, i.e., a non-penetrating injury with corneal laceration (partial-thickness corneal scar). This cohort study was conducted from July 2021 to August 2023. After first-stage treatment (stabilization of the post-traumatic visual defect confirmed by refraction and topography examination, corneal healing, and improvement of the corneal scar), the patients underwent the second-stage treatment, i.e., TCAT with a 20 to 45 s application of mitomycin C solution to avoid haze induction. After TCAT, the uncorrected distance visual acuity (UDVA) and best-corrected distance visual acuity (BCVA) were measured. Refractive astigmatism was assessed using autorefractometry. Topographic astigmatism was analyzed using corneal topography and pachymetry. The root mean square (RMS) of the higher-order aberration was calculated using Zernike coefficients. The patients’ corneal healing and refractive changes were monitored. Results: All patients were monitored for corneal healing and refractive changes and underwent the same second-stage treatment, which utilized TCAT to regularize the corneal surface and reduce higher-order aberrations (HOAs). The UDVA of patients 1, 2, 3 and 4 improved by 3, 7.5, 4 and 6 rows (Snellen chart), respectively. The resultant UDVA was 1.0, 0.9, 0.7 and 1.2, while BCVA was 1.0, 1.2, 1.0, and 1.5, respectively. Conclusions: TCAT regularized the patients’ corneal surfaces and reduced HOAs. We, therefore, conclude that TCAT may be a beneficial second-stage treatment for corneal trauma-induced astigmatism. Full article

We previously showed that selective suppression of CD44 in the corneal epithelium leads to structural abnormalities in the mouse cornea. Our comparative studies of young and aged ocular biopsies revealed that CD44 expression is downregulated in aged corneas, while leucine-rich repeats and immunoglobulin-like domain 1 (Lrig1+) stem cells remain preserved in the peripheral limbus. These findings suggest an age-related shift in the corneal stem cell compartmentalization, characterized by impaired CD44 expression in the central cornea and preservation of Lrig1+ stem cells in the limbus, which become the main stem cells in the senescent cornea. To investigate this further, we performed topical tamoxifen-inducible, diphtheria toxin-mediated ablation of Lrig1+ stem cells in mouse corneas. We then assessed both activated and non-activated beta-catenin expression in wild-type (WT) and CD44 knockout (CD44KO) mice, given that CD44 modulates the Wingless-related integration site (Wnt) pathway. Our results indicate that two distinct stem cell populations operate in the mouse cornea: Lrig1-derived stem cells and Wnt-activity/CD44-dependent stem cells. The Lrig1-derived cells act as a reservoir of quiescent stem cells that regenerate the cornea upon injury, whereas under homeostatic conditions, the Wnt-activity/CD44-dependent stem cells are primarily responsible for corneal renewal. In the aged cornea, the loss of CD44 expression leads to reduced Wnt signaling, making the tissue increasingly dependent on Lrig1+ stem cells for regeneration. In mice, Lrig1+ stem cells are capable of sustaining permanent corneal renewal, even in the absence of CD44. Full article

The therapeutic potential of exosomes (Exos), a subpopulation of extracellular vesicles (EVs) secreted by various cell types, has been broadly emphasized. Exos are endosome-derived membrane-bound vesicles 50–150 nm in size. Exos can be general or cell type-specific. Their contents enable them to function as multi-signaling and vectorized vehicles. Exos are important for maintaining cellular homeostasis. They are released into extracellular spaces, leading to uptake by neighboring or distant cells and delivering their contents to modulate cell signaling. Exos influence tissue responses to injury, infection, and disease by fusion with the target cells and transferring their cargo, including cytokines, growth and angiogenic factors, signaling molecules, lipids, DNA, mRNAs, and non-coding RNAs. They are implicated in various physiological and pathological conditions, including ocular surface events, such as corneal scarring, wound healing, and inflammation. Their biocompatibility, stability, low immunogenicity, and easy detectability in bodily fluids (blood, tears, saliva, and urine) make them promising tools for diagnosing and treating ocular diseases. The potential to engineer specific Exo cargos makes them outstanding therapeutic delivery vehicles. The objective of this review is to provide novel insights into the functions of Exo cargos and their applications as biomarkers and therapeutics, or targets in the cornea. Full article

Purpose: Pickleball, the fastest-growing sport in the United States, has seen a rapid increase in participation across all age groups, particularly among older adults. However, the sport introduces specific risks for ocular injuries due to the unique dynamics of gameplay and the physical properties of the pickleball. This study aims to explore the mechanisms of pickleball-related eye injuries, utilizing finite element modeling (FEM) to simulate ocular trauma and better understand injury mechanisms. Methods: A multi-modal approach was employed to investigate pickleball-related ocular injuries. Finite element modeling (FEM) was used to simulate blunt trauma to the eye caused by a pickleball. The FEM incorporated detailed anatomical models of the periorbital structures, cornea, sclera, and vitreous body, using hyperelastic material properties derived from experimental data. The simulations evaluated various impact scenarios, including changes in ball velocity, angle of impact, and material stiffness, to determine the stress distribution, peak strain, and deformation in ocular structures. The FEM outputs were correlated with clinical findings to validate the injury mechanisms. Results: The FE analysis revealed that the rigid, hard-plastic construction of a pickleball results in concentrated stress and strain transfer to ocular structures upon impact. At velocities exceeding 30 mph, simulations showed significant corneal deformation, with peak stresses localized at the limbus and anterior sclera. Moreover, our results show a significant stress applied to lens zonules (as high as 0.35 MPa), leading to potential lens dislocation. Posterior segment deformation was also observed, with high strain levels in the retina and vitreous, consistent with clinical observations of retinal tears and vitreous hemorrhage. Validation against reported injuries confirmed the model’s accuracy in predicting both mild injuries (e.g., corneal abrasions) and severe outcomes (e.g., hyphema, globe rupture). Conclusions: Finite element analysis provides critical insights into the biomechanical mechanisms underlying pickleball-related ocular injuries. The findings underscore the need for preventive measures, particularly among older adults, who exhibit age-related vulnerabilities. Education on the importance of wearing protective eyewear and optimizing game rules to minimize high-risk scenarios, such as close-range volleys, is essential. Further refinement of the FEM, including parametric studies and integration of protective eyewear, can guide the development of safety standards and reduce the socio-economic burden of these injuries. Full article

Background/Objective: A clinical need exists for more effective therapeutics and sustained drug delivery systems to promote ocular surface healing. This study tested the hypothesis that a novel biodegradable, thermoresponsive hydrogel loaded with the human recombinant (rh)MG53 protein, which we have demonstrated to promote corneal healing without fibrosis, would exhibit safety and biocompatibility in vitro and in vivo. Methods: Hydrogel optimization was performed based on varying concentrations of poloxamer 407, poloxamer 188, and hydroxypropyl methylcellulose. Hydrogels were characterized and potential toxicity was evaluated in vitro in cultured corneal epithelium, fibroblasts, and endothelium. In vivo safety and tolerability were assessed in mice and hydrogels were used to evaluate corneal healing following alkali injury. Results: The optimized hydrogel formulation did not result in any detrimental changes to the corneal cells and released functional rhMG53 protein for at least 24 h. In vivo rhMG53-loaded hydrogels improved re-epithelialization, reduced stromal opacification and vascularization, and promoted corneal nerve density. Mechanistically, rhMG53 reduced vascular endothelial cell migration and tube formation by inhibiting pSTAT3 signaling. Conclusions: Taken together, our poloxamer-based thermoresponsive hydrogel effectively released rhMG53 protein and enhanced multiple corneal healing outcomes. Full article

Human space exploration presents an unparalleled opportunity to study life in extreme environments—but it also exposes astronauts to physiological stressors that jeopardize key systems like vision. Corneal health, essential for maintaining precise visual acuity, is threatened by microgravity-induced fluid shifts, cosmic radiation, and the confined nature of spacecraft living environments. These conditions elevate the risk of corneal abrasions, infections, and structural damage. In addition, Spaceflight-Associated Neuro-Ocular Syndrome (SANS)—while primarily affecting the posterior segment—has also been potentially linked to anterior segment alterations such as corneal edema and tear film instability. This review examines these ocular challenges and assesses current mitigation strategies. Traditional approaches, such as terrestrial eye banking and corneal transplantation, are impractical for spaceflight due to the limited viability of preserved tissues, surgical complexities, anesthetic risks, infection potential, and logistical constraints. The paper explores emerging technologies like 3D bioprinting and stem cell-based tissue engineering, which offer promising solutions by enabling the on-demand production of personalized corneal constructs. Complementary advancements, including adaptive protective eyewear, bioengineered tear substitutes, telemedicine, and AI-driven diagnostic tools, also show potential in autonomously managing ocular health during long-duration missions. By addressing the complex interplay of environmental stressors and biological vulnerabilities, these innovations not only safeguard astronaut vision and mission performance but also catalyze new pathways for regenerative medicine on Earth. The evolution of space-based ophthalmic care underscores the dual impact of space medicine investments across planetary exploration and terrestrial health systems. Full article

Persistent corneal epithelial defects (PCEDs) are a challenging ocular condition characterized by the failure of complete corneal epithelial healing after an insult or injury, even after 14 days of standard care. There is a lack of therapeutics that target this condition and encourage re-epithelialization of the corneal surface in a timely and efficient manner. This review aims to provide an overview of current standards of management for PCEDs, highlighting novel, emerging treatments in this field. While many of the current non-surgical treatments aim to provide lubrication and mechanical support, novel non-surgical approaches are undergoing development to harness the proliferative and healing properties of human mesenchymal stem cells, platelets, lufepirsen, hyaluronic acid, thymosin ß4, p-derived peptide, and insulin-like growth factor for the treatment of PCEDs. Novel surgical treatments focus on corneal neurotization and limbal cell reconstruction using novel scaffold materials and cell-sources. This review provides insights into future PCED treatments that build upon current management guidelines. Full article

Cornea vascularisation is a significant cause of ocular morbidity. Disease or injury often triggers the development of new blood vessels in the cornea, compromising its clarity and impairing vision. Common causes of corneal neovascularisation include infections, chemical burns, and local and systemic inflammatory disorders. Topical corticosteroid eye drops remain the standard therapy; however, extended use of corticosteroids has been known to cause side-effects including cataracts and raised intraocular pressure. As such, an alternative therapy has been actively sought. Vascular endothelial growth factor (VEGF) is a major angiogenic factor implicated in neovascularisation. The success of anti-VEGF agents in managing leaking blood vessels in neovascular age-related macular degeneration provides an opportunity to explore its use in the treatment of corneal neovascularisation. The therapeutic potential of anti-VEGF agents has been evaluated in experimental models of corneal neovascularisation and clinical trials with variable results. Here, we review the study results and discuss the development of new strategies that may improve treatment outcomes for corneal neovascularisation. Full article

Background/Objectives: Clinically inactive corneal scars have repeatedly been shown to exhibit histological inflammation. This study aimed to evaluate the degree of histological inflammation in clinically inactive corneal scars of different origins and its correlation with graft rejection and failure following penetrating keratoplasty. Methods: The study included 205 primary corneal explants with clinically inactive central scars resulting from herpes simplex virus keratitis (HSV, n = 55), keratoconus (n = 39), mechanical trauma (n = 27), scrophulosa (n = 22) or other/unknown causes (n = 62). Central histological sections were categorized by the degree of inflammation, and an overall inflammation score (IS) was calculated. Results: HSV-associated scars exhibited a trend towards more graft rejection with higher IS (p = 0.074). Keratoconus-associated scars showed no IS-dependent differences in graft rejection or failure. The rejection rate in this group was 13/39. Scars resulting from mechanical trauma, such as perforating injuries, demonstrated a trend towards higher graft rejection (p = 0.15) and failure rates (p = 0.089) with increasing IS. The rejection rate in this group was 11/27. Scrophulosa-associated scars had significantly higher graft rejection rates (p = 0.041) at a lower cut-off of 0.06 compared to the cut-off of 0.36 for the other groups. Scars of other or unknown causes showed no IS-dependent differences in graft rejection or failure. Conclusions: Histological inflammation in HSV scars and scars resulting from mechanical trauma appeared to contribute to graft rejection. Despite low IS, the rejection rate in keratoconus scars and scars following mechanical trauma was unexpectedly high, indicating the presence of other influencing factors. While some correlations did not reach statistical significance due to small sample sizes in the subgroups, the observed trends should be considered clinically relevant. The study may have been “underpowered”, as histopathologically inflamed specimens with clinically inactive corneal scars are relatively rare. Full article

Background: Macrophomina phaseolina is an important phytopathogenic fungus affecting over 500 plant species worldwide. However, this fungus rarely causes disease in humans. Methods: We reported the first case of endophthalmitis due to M. phaseolina, describing microbiological diagnostic approaches. Also, we performed a systematic review of human infections by this plant pathogen in literature. We searched PubMed, Scopus, and Web of Science databases from inception to 31 December 2024. Results: Our case involved a male patient who presented with photophobia and pain in his right eye. His recent medical history revealed a superficial corneal injury caused by a metal burr three months prior, managed unsuccessfully by topical treatment and subsequent conjunctival flap surgery two months later. Ophthalmological and microbiological investigations, including microscopic examination, cultures, and DNA sequencing of ocular specimens, revealed M. phaseolina endophthalmitis. Despite intravenous and intravitreal antifungal therapy, the patient’s condition continued to worsen, eventually leading to enucleation. Regarding the literature review, we identified 12 additional cases of M. phaseolina human infections previously reported in literature. Overall, M. phaseolina was primarily associated with ocular infections (76.9% of cases), followed by skin infections and combined skin–joint infections. The majority of patients with M. phaseolina infection (63.6%) had no known immunosuppressive factors. Clinical outcomes were unfavorable in 46.15% of cases. Conclusions: M. phaseolina is an emerging cause of human infections, even in immunocompetent hosts, with a predilection for ocular infections. Further research is warranted to elucidate the pathogenesis of fungal infections caused by plant pathogens in humans. Full article

Corneal injury is prevalent in ophthalmology, with mild cases impacting vision and severe cases potentially resulting in permanent blindness. In clinical practice, standard treatments for corneal injury involve transplantation surgery combined with pharmacological therapy. However, surgical sutures exhibit several limitations, which can be overcome using tissue adhesives. With recent advances in biomedical materials, the use of ophthalmic tissue adhesives has expanded beyond wound closure, including tissue filling and drug delivery. Furthermore, the use of tissue adhesives has demonstrated promising outcomes in drug delivery, ophthalmic disease diagnosis, and biological scaffolds. This study briefly introduces common adhesion mechanisms and their applications in ophthalmology, aiming to increase interest in tissue adhesives and clinical ophthalmic treatment. Full article

Background/Objectives: The objective of the present study was to examine the unidentified effects that RHO-associated coiled-coil-containing protein kinase 1 and 2 antagonists exert on the transforming growth factor beta2-induced epithelial–mesenchymal transition of the human corneal stroma. Methods: In the presence or absence of pan-RHO-associated coiled-coil-containing protein kinase inhibitors, ripasudil or Y27632 and RHO-associated coiled-coil-containing protein kinase 2 inhibitor, KD025, we analyzed the following: (1) planar proliferation caused by trans-endothelial electrical resistance and the cellular metabolic characteristics of the two-dimensional cultures of human corneal stroma fibroblasts; (2) the physical properties of a three-dimensional human corneal stroma fibroblasts spheroid; and (3) the gene expressions and their regulators in the extracellular matrix, along with the tissue inhibitors of metalloproteinases and matrix metalloproteinases and the endoplasmic reticulum stress-related factors of the two-dimensional and three-dimensional cultures in human corneal stroma fibroblasts. Results: Exposure to 5 nM of the transforming growth factor beta2 markedly increased the trans-endothelial electrical resistance values as well as the metabolic function in two-dimensional cultures of human corneal stroma fibroblasts. With an increase in stiffening, this exposure also reduced the size of three-dimensional human corneal stroma fibroblast spheroids, which are typical cellular phenotypes of the epithelial–mesenchymal transition. Both pan-RHO-associated coiled-coil-containing protein kinase inhibitors and RHO-associated coiled-coil-containing protein kinase 2 inhibitors substantially modulated these transforming growth factor beta2-induced effects, albeit in a different manner. Gene expression analysis supported such biological alterations via either with transforming growth factor beta2 alone or with the RHO-associated coiled-coil-containing protein kinase inhibitors variants with the noted exception being the transforming growth factor beta2-induced effects toward the three-dimensional human corneal stroma fibroblast spheroid. Conclusions: The findings presented herein suggest the following: (1) the epithelial–mesenchymal transition could be spontaneously evoked in the three-dimensional human corneal stroma fibroblast spheroid, and, therefore, the epithelial–mesenchymal transition induced by transforming growth factor beta2 could differ between two-dimensional and three-dimensional cultured HCSF cells; and (2) the inhibition of ROCK1 and 2 significantly modulates the transforming growth factor beta2-induced an epithelial–mesenchymal transition in both two-dimensionally and three-dimensionally cultured human corneal stroma fibroblasts, albeit in a different manner. Full article

Mustard gas keratopathy (MGK), a complication of exposure to sulfur mustard, is a blinding ocular surface disease involving key cellular pathways, including apoptosis, oxidative stress, and inflammation. Recent studies indicate that cellular senescence contributes to the pathophysiology of mustard gas toxicity. This study aimed to assess senescence and stress-related pathways—particularly mitogen-activated protein kinase (MAPK) signaling—in nitrogen mustard (NM)-induced corneal injury. In vitro, primary human corneal epithelial (P-HCECs), primary human corneal mesenchymal stromal cells (hcMSCs), and human corneal–limbal epithelial cell (HCLE) lines were exposed to varying concentrations of NM. The results demonstrated a dose-dependent increase in cellular senescence, characterized by reduced Ki67 expression, elevated p16, and p21 mRNA levels, as well as activation of the MAPK pathway activation. Treatment with a selective p38-MAPK inhibitor significantly reduced senescence markers and improved cell proliferation following exposure to NM. Overall, these studies indicate that NM exposure triggers cellular senescence and stress-related MAPK signaling, while p38-MAPK inhibition mitigates these effects, suggesting a potential therapeutic strategy. Full article

Endothelial–mesenchymal transition (EnMT) is the transversion of endothelial cells to mesenchymal cells under certain physiological or pathological conditions. When EnMT occurs in the corneal endothelium, corneal endothelial cells (CECs) lose their normal function and thus cannot maintain corneal clarity. Studies have shown that the mechanism of EnMT in CECs involves the transforming growth factor-β (TGF-β) signaling pathway, and one of the important inhibitors of the TGF-β/Smad2/3 pathway is sirtuin-1 (SIRT1). In this study, we used a rat model of corneal endothelium injury and TGF-β1-treated human CECs to induce EnMT, aiming to explore whether SIRT1 activation inhibits corneal EnMT in vivo and in vitro. SIRT1 was activated and suppressed using resveratrol (RSV) and EX527, respectively. The endothelial markers and mesenchymal markers were measured by immunofluorescence and Western blot assays. Co-immunoprecipitation was used to detect the interaction between SIRT1 and Smad2/3. The results showed that after mechanical injury, the group treated with RSV-activated SIRT1 regained corneal transparency and recovered from edema faster than the control group. Moreover, RSV-activated SIRT1 downregulated the expression levels of alpha smooth muscle actin (α-SMA), vimentin, and Snail and upregulated the expression levels of E-cadherin and Na⁺/K⁺-ATPase both in vivo and in vitro, but these effects were reversed when SIRT1 was inhibited by EX527. SIRT1 also upregulated the expression levels of TGF-β receptor 1 and phosphorylated Smad2/3. The interaction between SIRT1 and Smad2/3 in vitro was confirmed by co-immunoprecipitation. Overall, our results indicate that SIRT1 activation inhibits corneal EnMT via the TGF-β/Smad2/3 pathway, which may be a potential therapeutic target for corneal endothelium dysfunction. Full article