Inhibition of matrix metalloproteases by a chemical cross-linker to halt the corneal degradation in keratoconus.

The need for better and simpler alternative crosslinking strategies to treat keratoconus (KC) is becoming essential as there is only a single approved way to treat it. Recently, conventional UV-A Riboflavin crosslinking is proven to have some disadvantages such as causing damage to the corneal endothelium and inducing keratocyte apoptosis. A chemical cross-linker (CXL) using carbodiimide chemistry and an octanedioic acid spacer is found effective in stiffening the cornea and has the potential to be developed as an alternative therapy to halt KC progression.

Melanin depletion affects Aspergillus flavus conidial surface proteins, architecture, and virulence.

Melanin is an Aspergillus flavus cell wall component that provides chemical and physical protection to the organism. However, the molecular and biological mechanisms modulating melanin-mediated host-pathogen interaction in A. flavus keratitis are not well understood.

Myocilin Mutation N480K Leads to Early Onset Juvenile and Adult-onset Primary Open Angle Glaucoma in a Six Generation Family.

Prcis: A pathogenic autosomal dominant MYOC mutation N480K detected in 6 generations of an Indian family is primarily responsible for juvenile open angle glaucoma (JOAG) and adult-onset primary open angle glaucoma (POAG), emphasizing the importance of screening this mutation at a younger age.

Purpose: To screen myocilin mutations in a large South Indian family with early-onset JOAG and adult-onset POAG.

Methods: In a large South Indian family with 20 members, 8 members diagnosed as JOAG, 7 members as POAG, 4 members as JOAG suspect, and 1 member as POAG suspect were screened for myocilin ( MYOC) mutations using Sanger sequencing.

Comparative proteomics of proliferative diabetic retinopathy in people with Type 2 diabetes highlights the role of inflammation, visual transduction, and extracellular matrix pathways.

Purpose: To explore the vitreous humor proteome from type 2 diabetes subjects with proliferative diabetic retinopathy (PDR) in the Indian population.

Methods: We performed mass spectrometry-based label-free quantitative analysis of vitreous proteome of PDR (n = 13) and idiopathic macular hole (IMH; control) subjects (n = 14). Nine samples of PDR and 10 samples of IMH were pooled as case and control, respectively, and compared.

Profiling of idiopathic macular hole vitreous proteome identifies the role of extracellular matrix remodelling, epithelial-mesenchymal transformation and unfolded protein-response pathways.

Purpose: To analyze and describe the proteome of the vitreous humour in eyes with idiopathic macular holes.

Methods: We performed mass spectrometry (MS)-based label-free quantitative analysis of the vitreous proteome of idiopathic macular hole (IMH) and control donor vitreous. Comparative quantification was performed using SCAFFOLD software which calculated fold changes of differential expression.

Comparative proteome analysis identifies species-specific signature proteins in Aspergillus pathogens.

Aspergillus flavus and Aspergillus fumigatus are important human pathogens that can infect the lung and cornea. During infection, Aspergillus dormant conidia are the primary morphotype that comes in contact with the host. As the conidial surface-associated proteins (CSPs) and the extracellular proteins during the early stages of growth play a crucial role in establishing infection, we profiled and compared these proteins between a clinical strain of A.

Mycobacterium leprae hsp18 promoter-EGFP transcriptional fusion construct: Environmental stress and strain-specific expression.

The Hsp18 protein is a major T-cell antigen of Mycobacterium leprae belonging to the family of small heat-shock proteins. The protein is specifically regulated at post-translational level during the intracellular growth of M. leprae within macrophages due to auto-phosphorylation, indicating its importance in the survival of the bacterium.

Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy.

Importance: It is a global challenge to provide regular retinal screening for all people with diabetes to detect sight-threatening diabetic retinopathy (STDR).

Objective: To determine if circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect STDR.

Design, Setting, And Participants: This cross-sectional study collected data from October 22, 2018, to December 31, 2021.

Inhibition of Aldose Reductase by Novel Phytocompounds: A Heuristic Approach to Treating Diabetic Retinopathy.

Aldose reductase (ALR2) activation in the polyol pathway has been implicated as the primary mechanism for the progression of diabetic retinopathy. Most of the aldose reductase inhibitors (ARIs), used for the treatment of diabetic complications, were withdrawn due to ineffective treatment and adverse side effects caused by nonspecificity. Epalrestat, a carboxylic acid inhibitor, is the only ARI used for the treatment of diabetic neuropathy, though associated with minor side effects to 8% of the treated population.

Expression of immune response genes in human corneal epithelial cells interacting with Aspergillus flavus conidia.

Background: Aspergillus flavus, one of the causative agents of human fungal keratitis, can be phagocytosed by human corneal epithelial (HCE) cells and the conidia containing phagosomes mature into phagolysosomes. But the immunological responses of human corneal epithelial cells interacting with A. flavus are not clear.

Chemical Cross-Linking of Corneal Tissue to Reduce Progression of Loss of Sight in Patients With Keratoconus.

Purpose: We aimed to develop a novel chemical cross-linker treatment for keratoconus by reacting dicarboxylic acid spacer molecules and amine functional groups on protein structure of the tissue using carbodi-imide chemistry. We propose this as an alternative to conventional cross-linking treatment for keratoconus.

Methods: The study involved optimization of the cross-linker formulation.

Human Corneal Epithelial Cells Internalize Aspergillus flavus Spores by Actin-Mediated Endocytosis.

Human corneal epithelial (HCE) cells play a significant role in the innate immune response by secreting cytokines and antimicrobial peptides when they encounter fungal pathogens. But the detailed mechanism of attachment and engulfment of the fungal conidia by HCE cells is not well understood. Here, we show the phagocytosis of conidia by RCB2280 cells and primary HCE cultures using confocal microscopy and proteomic analysis of conidium-containing phagosomes.

Proteomic Signatures of Healthy Intervertebral Discs From Organ Donors: A Comparison With Previous Studies on Discs From Scoliosis, Animals, and Trauma.

Objective: To catalog and characterize the proteome of normal human intervertebral disc (IVD).

Methods: Nine magnetic resonance imaging (MRI) normal IVDs were harvested from 9 different brain dead yet alive voluntary organ donors and were subjected to electrospray ionization-liquid chromatography tandem mass spectrometry (ESI-LC-MS/MS) acquisition.

Results: A total of 1,116 proteins were identified.

Differential Interactions of Serum and Bronchoalveolar Lavage Fluid Complement Proteins with Conidia of Airborne Fungal Pathogen Aspergillus fumigatus.

Even though both cellular and humoral immunities contribute to host defense, the role played by humoral immunity against the airborne opportunistic fungal pathogen has been underexplored. In this study, we aimed at deciphering the role of the complement system, the major humoral immune component, against Mass spectrometry analysis of the proteins extracted from conidial (asexual spores and infective propagules) surfaces opsonized with human serum indicated that C3 is the major complement protein involved. Flow cytometry and immunolabeling assays further confirmed C3b (activated C3) deposition on the conidial surfaces.

Local Activation of the Alternative Pathway of Complement System in Mycotic Keratitis Patient Tear.

are the predominant causative agents of mycotic keratitis in the tropical part of the world. Tear proteins play a major role in the innate immune response against these fungal infections as has been shown by the presence of complement proteins and neutrophil extracellular trap proteins in keratitis patients tear. In this study, we established the presence of the components of the alternate pathway of complement system and their functional state in the tear film of mycotic keratitis patients.

Molecular Mimicry between Betaine Aldehyde Dehydrogenase of and Retinal Dehydrogenase 1 of Human Lens: A Potential Trigger for Cataract Formation in Leptospiral Uveitis Patients.

: Rapidly progressing cataract is one of the ocular manifestations in leptospiral uveitis patients. We examined whether molecular mimicry between the leptospira antigens and lens proteins exists that could result in cataract in these patients.: Immunoblot analysis using patient sera was done with proteins from normal lens and cataract lens from leptospiral uveitis patients and the cross-reacting lens proteins were identified by mass spectrometry analysis.

Dataset for the spore surface proteome and hydrophobin A/RodA proteoforms of A.flavus.

Fungal keratitis is a major sight-threatening corneal infection: and mycotic keratitis is more common in tropical parts of the world including India. and are the predominant causative agents of corneal infection. We extracted conidial surface proteins of from saprophyte and clinical isolates and analyzed the proteins using high resolution mass spectrometry.

Quantitative profiling of tear proteome reveals down regulation of zinc alpha-2 glycoprotein in Aspergillus flavus keratitis patients.

Corneal mycotic ulceration is predominantly due to Aspergillus and Fusarium solani infection in tropical countries. In this study, we examined the proteome profile of tear samples from A. flavus keratitis patients at various stages of infection.

Identification of the proteoforms of surface localized Rod A of Aspergillus flavus and determination of the mechanism of proteoform generation.

Fungal keratitis is a serious, potentially sight-threatening corneal infection that is more prevalent in the tropical parts of the world including India, and A. flavus and Fusarium solani are the predominant etiological agents. The surface of fungal conidia is covered by hydrophobin family proteins, effectively masking the conidial antigens from immune cells.

Data set of induced alterations in tear proteome: Understanding the pathogen-induced host response to fungal infection.

Fungal keratitis is one of the leading causes of blindness in the tropical countries affecting individuals in their most productive age. The host immune response during this infection is poorly understood. We carried out comparative tear proteome analysis of keratitis patients and uninfected controls.

Aspergillus flavus induced alterations in tear protein profile reveal pathogen-induced host response to fungal infection.

Unlabelled: Aspergillus flavus and Fusarium sp. are primary causative agents of keratitis that results in corneal tissue damage leading to vision loss particularly in individuals from the tropical parts of the world. Proteins in the tear film collected from control and keratitis patients was profiled and compared.

Data set for the mass spectrometry based exoproteome analysis of Aspergillus flavus isolates.

Aspergillus flavus is one of the predominant causative organisms of mycotic keratitis in tropical parts of the world. Extracellular proteins are the earliest proteins that come in contact with the host and have a role in the infection process. Exoproteins of A.

Exoproteome of Aspergillus flavus corneal isolates and saprophytes: identification of proteoforms of an oversecreted alkaline protease.

Unlabelled: Aspergillus flavus infects the human eye leading to keratitis. Extracellular proteins, the earliest proteins that come in contact with the host and virulence related exoproteins, were identified in the fungus isolated from infected cornea. Virulence of the corneal isolates was tested in the Galleria mellonella larvae model and those isolates showing higher virulence were taken for subsequent exoproteome analysis.