Archana Padmanabhan Nair1, Sharon D'Souza2, Rohit Shetty2, Prerna Ahuja2, Gairik Kundu2, Pooja Khamar2, Zelda Dadachanji2, Prajakta Paritekar2, Pavitra Patel2, Mor M Dickman3, Rudy Mma Nuijts4, Rajiv R Mohan5, Arkasubhra Ghosh6, Swaminathan Sethu7. 1. GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India; Manipal Academy of Higher Education, Manipal, India. 2. Department of Cornea and Refractive Surgery, Narayana Nethralaya, Bangalore, India. 3. University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands; MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, the Netherlands. 4. University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands. 5. Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA; Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO, USA; Harry S Truman Veterans' Memorial Hospital, Columbia, MO, USA. Electronic address: mohanr@health.missouri.edu. 6. GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India; Singapore Eye Research Institute, Singapore. Electronic address: arkasubhra@narayananethralaya.com. 7. GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India. Electronic address: swaminathansethu@narayananethralaya.com.
Abstract
PURPOSE: Aberrant inflammation and immune dysregulation are known pathogenic contributors in dry eye disease (DED). Aim of the study was to determine the proportions of immune cell subsets on the ocular surface (OS) of DED patients. METHODS: 15 healthy controls (22 eyes) and 48 DED subjects (36 eyes with evaporative DED - EDED; 60 eyes with aqueous deficient DED - ADED) were included in the study. Tear break up time (TBUT), Schirmer's test 1 (ST1), corneal staining (CS) and ocular surface disease index (OSDI) scoring were recorded. OS wash was used to collect immune cells on the OS of study subjects. The cells immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer-NK cells and T cell subsets (CD4; CD8; double positive-DP; gamma delta-γδ and NK T cells). RESULTS: Significantly higher proportions of leukocytes, neutrophils, CD4 T cells, CD8 T cells, DP T cells and CD4/CD8 T cells ratio were observed in EDED and/or ADED patients. Significantly higher proportions of neutrophils and lower proportions of NK cells were observed in ADED subjects with corneal staining compared to those without and controls. Neutrophils/NK cells ratio was significantly higher in EDED and ADED subjects compared to controls. Correlation analysis revealed pathological relationships between proportions of leukocytes, neutrophils, CD4 T cells and Neutrophil/NK cells ratio with DED clinical parameters. CONCLUSION: OS immune cell subset proportion changes in DED patients were associated with DED types and severity. The data suggests the potential for a new generation of therapies targeting immune cells on the ocular surface.
PURPOSE: Aberrant inflammation and immune dysregulation are known pathogenic contributors in dry eye disease (DED). Aim of the study was to determine the proportions of immune cell subsets on the ocular surface (OS) of DED patients. METHODS: 15 healthy controls (22 eyes) and 48 DED subjects (36 eyes with evaporative DED - EDED; 60 eyes with aqueous deficient DED - ADED) were included in the study. Tear break up time (TBUT), Schirmer's test 1 (ST1), corneal staining (CS) and ocular surface disease index (OSDI) scoring were recorded. OS wash was used to collect immune cells on the OS of study subjects. The cells immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer-NK cells and T cell subsets (CD4; CD8; double positive-DP; gamma delta-γδ and NK T cells). RESULTS: Significantly higher proportions of leukocytes, neutrophils, CD4 T cells, CD8 T cells, DP T cells and CD4/CD8 T cells ratio were observed in EDED and/or ADED patients. Significantly higher proportions of neutrophils and lower proportions of NK cells were observed in ADED subjects with corneal staining compared to those without and controls. Neutrophils/NK cells ratio was significantly higher in EDED and ADED subjects compared to controls. Correlation analysis revealed pathological relationships between proportions of leukocytes, neutrophils, CD4 T cells and Neutrophil/NK cells ratio with DED clinical parameters. CONCLUSION: OS immune cell subset proportion changes in DED patients were associated with DED types and severity. The data suggests the potential for a new generation of therapies targeting immune cells on the ocular surface.
Authors: Konstantinos Kagkelaris; Mohamed A El Mubarak; Panagiotis Plotas; Dimitris Panaretos; George D Panayiotakopoulos; Gregory B Sivolapenko; Constantinos D Georgakopoulos Journal: Medicina (Kaunas) Date: 2022-08-01 Impact factor: 2.948