Ocular Surface

When noise becomes signal: A study of blink rate using an eye tracker
Nagarajan K, Ravi K, Periakaruppan SP and Satgunam P
Although blink rate is considered important for digital eye strain and dry eye conditions, its assessment has been mostly manual. This study aimed at quantifying blink rate automatically using the Eyelink 1000 Plus eye tracker and comparing it with manual counting. Additionally, blink rate was correlated with reading eye movements and reading speed.
Cell Death Pathways in Dry Eye Disease: Insights into Ocular Surface Inflammation
Li J, Bao X, Guo S, Huang Y, Huang C, Hu J and Liu Z
Dry eye disease (DED) is increasingly prevalent, with inflammation playing a crucial role in its pathogenesis. Severe cases of DED result in significant ocular discomfort and visual impairment due to damage and loss of ocular surface epithelial cells. The precise mechanisms underlying the loss of these epithelial cells remain a subject of ongoing research and debate. Programmed cell death (PCD) mechanisms, including pyroptosis, apoptosis, and necroptosis, are known to be critical in maintaining ocular surface homeostasis and responding to stressors in DED. The concept of PANoptosis, which integrates elements of various PCD pathways, has been implicated in the development of numerous systemic diseases, including infections, cancer, neurodegenerative, and inflammatory conditions. It also provides novel insights into the inflammatory processes underlying DED. This review highlights the crosstalk of PCD pathways in DED, particularly the significance of PANoptosis in ocular inflammation and its potential as a therapeutic target for more effective interventions.
Readership awareness series - paper 14: The submission Dilemma - How to choose a journal?
Ali MJ and Djalilian A
Adipose-derived mesenchymal stromal cells: A study on safety and efficacy in ocular inflammation
Rusch RM, Inagaki E, Taniguchi H, Sakakura S, Tamai R, Nonaka H, Shimizu S, Sato S, Ogawa Y, Masatoshi H, Negishi K, Okano H and Shimmura S
This study explores the application of adipose-derived mesenchymal stromal cells (adMSCs) as a therapy for ocular inflammatory diseases utilizing a chronic GVHD model.
A Tribute to Dr. Alison McDermott and her Contributions to the Ocular Surface
Meibomian gland tortuosity, truncation, and dilation in paediatric dry eye disease: A multi-centre, investigator-masked, cross-sectional study
Wang MTM, Wolffsohn JS, Kim JS, Speakman S, Pritchard E, Power B and Craig JP
Big-bubble DALK: A technique in evolution
Moramarco A, Gardini L, Di Mola I, di Geronimo N, Iannetta D, Romano V, Hannush SB and Fontana L
Deep anterior lamellar keratoplasty (DALK) is considered a valuablealternative to penetrating keratoplasty (PK) for treatingcorneal disordersthat do not involve theendothelium. DALK preserves the host endothelium, eliminating the risk of endothelial rejection and reducing the risk of late graft failure due to endothelial decay. Despite its not recent introduction, DALK has been considered a difficult, lengthy, and poorly reproducible procedure, limiting its adoption worldwide. With the introduction of the big-bubble technique (BBT) the reproducibility and the time required to complete the procedure were significantly improved, encouraging many surgeons to approach DALK. With BBT air is injected into the stroma to induce separation between the layers of the cornea, facilitating the separation of the diseased or scarred stroma from the healthy endothelium; this allows the creation of a graft-host interface of pristine optical quality, granting clinical results equal to those obtained with PK.Understanding the anatomy and physics behind the big bubble (BB) formation is crucial for thesurgical success of this technique. The discovery of the pre-Descemet's layer (Dua's layer)played a significant role in understanding the principles behindBBformation, considerablyimpacting the safety and reproducibility of the technique. BB formation is influenced by preoperative pathology, trephination size, and instruments used for air injection.Continue advancements have helped to refine BBT's efficacy and reproducibility, broadening its applicability in corneal transplantation whenever the endothelium is healthy.This review provides a detailed account of the procedural steps involved in DALK using the BBT, addressing the most common challenges, highlightingtechnical innovations, and handlingthe most frequent complications.
Meibomian gland lipid alterations and ocular surface sequela in Awat2 knockout murine model of meibomian gland dysfunction and evaporative dry eye disease
Hisey EA, Wong S, Park S, Gamarra KA, Adelman SA, Knickelbein KE, Quan M, Ferneding MH, McCorkell M, Daley N, Ureno V, Le S, Ardon M, Williams L, Puentes B, Bowman M, Motta MJ, Pham HQH, Wilkerson A, Yuksel S, Jester JV, Thomasy SM, Morgan JT, Butovich IA and Leonard BC
There is an urgent need for animal models of meibomian gland dysfunction (MGD) and evaporative dry eye disease (EDED) to understand their pathophysiology and investigate novel therapeutics. This study sought to further define the acyl-CoA: wax alcohol acyltransferase 2 knockout (Awat2 KO) mouse as a model of EDED using a combination of novel clinical, biochemical, and biophysical endpoints.
Mineralocorticoid receptor expression and the effects of the mineralocorticoid receptor antagonist spironolactone in a murine model of graft-versus-host disease
Sato S, Ogawa Y, Wong CW, Le HL, Yee RW, Gombos DS, Negishi K and Hirayama M
The topical administration of spironolactone, a mineralocorticoid receptor antagonist (MRA) improves dry eye symptoms in patients with ocular graft-versus-host disease (GVHD); however, the detailed mechanism remains unclear. This study aimed to investigate the effects of spironolactone eyedrops on the ocular surface using a chronic GVHD (cGVHD) mouse model and to determine the expression of the mineralocorticoid receptor (MR).
Target specification and therapeutic potential of extracellular vesicles for regulating corneal angiogenesis, lymphangiogenesis, and nerve repair
Pedersen C, Chen VT, Herbst P, Zhang R, Elfert A, Krishan A, Azar DT, Chang JH, Hu WY, Kremsmayer TP, Jalilian E, Djalilian AR, Guaiquil VH and Rosenblatt MI
Extracellular vesicles, including exosomes, are small extracellular vesicles that range in size from 30 nm to 10 μm in diameter and have specific membrane markers. They are naturally secreted and are present in various bodily fluids, including blood, urine, and saliva, and through the variety of their internal cargo, they contribute to both normal physiological and pathological processes. These processes include immune modulation, neuronal synapse formation, cell differentiation, cancer metastasis, angiogenesis, lymphangiogenesis, progression of infectious disease, and neurodegenerative disorders like Alzheimer's and Parkinson's disease. In recent years, interest has grown in the use of exosomes as a potential drug delivery system for various diseases and injuries. Importantly, exosomes originating from a patient's own cells exhibit minimal immunogenicity and possess remarkable stability along with inherent and adjustable targeting capabilities. This review explores the roles of exosomes in angiogenesis, lymphangiogenesis, and nerve repair with a specific emphasis on these processes within the cornea. Furthermore, it examines exosomes derived from specific cell types, discusses the advantages of exosome-based therapies in modulating these processes, and presents some of the most established methods for exosome isolation. Exosome-based treatments are emerging as potential minimally invasive and non-immunogenic therapies that modulate corneal angiogenesis and lymphangiogenesis, as well as enhance and accelerate endogenous corneal nerve repair.
"En bloc" combined 270-degree keratolimbal allograft with central lamellar keratoplasty for severe limbal stem cell deficiency secondary to mustard gas exposure
Karimian F, Hassanpour K, Arzaghi M and Karjou Z
Severe limbal stem cell deficiency (LSCD) resulting from chronic and delayed-onset mustard gas keratopathy (MGK) presents substantial management challenges. This article introduces an "en bloc" surgical procedure combining a 270-degree keratolimbal allograft (KLAL) with central lamellar keratoplasty (CLK) as a novel approach to treat this condition.
Simple limbal epithelial transplantation versus cultivated limbal epithelial transplantation in ocular burns
Sharma N, Venugopal R, Mohanty S, Priyadarshini K, Nagpal R, Singhal D, Bari A, Dada T, Maharana PK, Agarwal T and Upadhyay AD
To compare the outcomes of simple limbal epithelial transplantation (SLET) with cultivated limbal epithelial transplantation (CLET) for the management of total limbal stem cell deficiency (LSCD) in eyes with unilateral ocular burns.
Preventing and treating neurotrophic keratopathy by a single intrastromal injection of AAV-mediated gene therapy
Cong L, Qi B, Ma W, Ren Z, Liang Q, Zhou Q, Zhang BN and Xie L
Neurotrophic keratopathy (NK) is a degenerative corneal condition resulting from corneal nerve injury. Current therapies, including the recombinant human nerve growth factor (rhNGF) therapy, requires continuous administration. This study aims to develop a novel and highly effective gene therapy strategy for the prevention and treatment of NK.
Cytarabine chemotherapy induces meibomian gland dysfunction
Liu R, Xue J, Han J, Tu M, Wang W, Chen Z, Qian X, Xiao B and Liang L
Cytarabine (Ara-C) chemotherapy causes symptoms resembling meibomian gland dysfunction (MGD), suggesting potential associations between Ara-C and MGD. In this study, the pathological effects of Ara-C on MGD were investigated in a rodent model.
Changes in conjunctival mononuclear phagocytes and suppressive activity of regulatory macrophages in desiccation induced dry eye
Alam J, Yaman E, de Paiva CS, Li DQ, Villalba Silva GC, Zuo Z and Pflugfelder SC
To evaluate the effects of dry eye on conjunctival immune cell number and transcriptional profiles with attention to mononuclear phagocytes.
Epidemiology and risk factors for the development of cicatrizing conjunctivitis in chronic ocular graft-versus-host disease
Kantor NB, Sepulveda-Beltran PA, Valdés-Arias D, Locatelli EVT, Mulpuri L, Gunawardene AN, Amescua G, Perez VL, Tonk R, Wang T and Galor A
To evaluate the incidence of chronic cicatrizing conjunctivitis (CCC) and its associated risk factors in the context of chronic ocular graft-vs-host disease (coGVHD).
Diagnostic performance and optimal cut-off values for tear film lipid layer grading and thickness in dry eye disease: An investigator-masked, randomised crossover study
Wang MTM, Power B, Xue AL and Craig JP
Development of human amniotic epithelial cell-derived extracellular vesicles as cell-free therapy for dry eye disease
Yi S, Kim J, Kim MJ, Yae CG, Kim KH and Kim HK
This study aimed to investigate the therapeutic potential of extracellular vesicles (EVs) derived from human amniotic epithelial cells (hAEC-EVs) for Dry Eye Disease (DED) treatment.
BMAL1 deficiency provokes dry mouth and eyes by down-regulating ITPR2/3
Zhang X, Chen G, He Y, Tang Q, Yin Y and Jie Y
Secretory glands, responsible for tears and saliva production, play essential roles in maintaining ocular and oral well-being. Disruptions in gland secretion can arise from various factors, including rhythm disturbances associated with sleep disorders. However, the underlying mechanisms governing these disruptions remain largely unexplored. We demonstrate that BMAL1, a core component of the circadian system, plays a critical role in regulating secretory gland secretion. Loss of BMAL1 induces vacuolation and atrophy phenotypes in acinar cells, subsequently leading to cell apoptosis and gland hypofunction, but does not cause Sjogren's syndrome, which is characterized by localized inflammatory cell infiltration. Mechanically, BMAL1 directly modulates the transcription of ITPR2 and ITPR3, thereby altering the secretion of Lactoferrin and Lysozyme. Restoration of ITPR2 and ITPR3 expression in Bmal1-deficient rats effectively alleviated the symptoms of lacrimal and parotid glands secretory dysfunction and significantly reduced dry mouth and dry eye conditions in rhythm-disordered rats. These findings highlight the essential role of BMAL1 in regulating salivary and lacrimal gland secretion and suggest a novel therapeutic approach for treating dry mouth and dry eyes associated with rhythm disorders.
Metabolomics of basal tears in amyotrophic lateral sclerosis: A cross-sectional study
Khanna RK, Catanese S, Mortemousque G, Dupuy C, Lefevre A, Emond P, Beltran S, Gissot V, Pisella PJ, Blasco H and Corcia P
Amyotrophic lateral sclerosis (ALS) clinical variability, along with the lack of conclusive diagnostic instruments, result in average diagnosis delays of 9 months. This study aimed to assess whether metabolomic profiling of basal tears in ALS patients could act as a biological marker for diagnosing ALS, predicting prognosis, and discriminating between endophenotypes.
Recent advances in NLRP3 inflammasome in corneal diseases: Preclinical insights and therapeutic implications
Ge J, Li X, Xia Y, Chen Z, Xie C, Zhao Y, Chen K, Shen Y and Tong J
NLRP3 inflammasome is a cytosolic multiprotein complex formed in response to exogenous environmental stress and cellular damage. The three major components of the NLRP3 inflammasome are the innate immunoreceptor protein NLRP3, the adapter protein apoptosis-associated speck-like protein containing a C-terminal caspase activation and recruitment domain, and the inflammatory protease enzyme caspase-1. The integrated NLRP3 inflammasome triggers the activation of caspase-1, leading to GSDMD-dependent pyroptosis and facilitating the maturation and release of inflammatory cytokines, namely interleukin (IL)-18 and IL-1β. However, the inflammatory responses mediated by the NLRP3 inflammasome exhibit dual functions in innate immune defense and cellular homeostasis. Aberrant activation of the NLRP3 inflammasome matters in the etiology and pathophysiology of various corneal diseases. Corneal alkali burn can induce pyroptosis, neutrophil infiltration, and corneal angiogenesis via the activation of NLRP3 inflammasome. When various pathogens invade the cornea, NLRP3 inflammasome recognizes pathogen-associated molecular patterns or damage-associated molecular patterns to engage in pro-inflammatory and anti-inflammatory mechanisms. Moreover, chronic inflammation and proinflammatory cascades mediated by the NLRP3 inflammasome contribute to the pathogenesis of diabetic keratopathy. Furthermore, overproduction of reactive oxygen species, mitochondrial dysfunction, and toll-like receptor-mediated activation of nuclear factor kappa B drive the stimulation of NLRP3 inflammasome and participate in the progression of dry eye disease. However, there still exist controversies regarding the regulatory pathways of the NLRP3 inflammasome. In this review, we provide a comprehensive overview of recent advancements in the function of NLRP3 inflammasome in corneal diseases and its regulatory pathways primarily through studies using animal models. Furthermore, we explore prospects for pharmacologically targeting pathways associated with NLRP3.