Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0314719 (dry eye)
 2,625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PURPOSE. Given that dry eye disease (DED) is associated with T cell-mediated inflammation of the ocular surface and that PD-L1 is an important negative or inhibitory regulator of immune responses constitutively expressed at high levels by corneal epithelial cells, the authors studied the expression and function of PD-L1 in DED. METHODS. Dry eye was induced in untreated wild-type mice, PD-L1(-/-) mice, and wild-type mice treated with anti-PD-L1 antibody by exposing these mice to a desiccating environment in the controlled environment chamber modified with subcutaneous administration of scopolamine. Real-time PCR was used to quantify the expression of chemokine gene transcript levels of multiple CC and CXC chemokine ligands and receptors. Epifluorescence microscopy was used to evaluate corneal infiltration of CD3(+) T cells after immunohistochemical staining. RESULTS. The increased expression of specific chemokine ligands and receptors in PD-L1(-/-) corneas of normal mice is associated with significant increases in T-cell homing into these corneas. Similar, and more enhanced, increases in T-cell infiltration were observed in PD-L1(-/-) DED mice or DED mice treated with anti-PD-L1 antibody compared with controls. In addition, the authors found significantly decreased expression of PD-L1 by corneal epithelial cells in DED and significantly increased corneal fluorescein staining score with PD-L1 functional blockade using anti-PD-L1 antibody. CONCLUSIONS. Downregulation of corneal epithelial PD-L1 amplifies dry eye-associated corneal inflammation and epitheliopathy by increasing the expression of chemokine ligands and receptors that promote T-cell homing to the ocular surface.
 ...
PMID:Regulation of T-cell chemotaxis by programmed death-ligand 1 (PD-L1) in dry eye-associated corneal inflammation. 2001 73

Programmed death receptor-1 (PD-1) and its ligand, PD-L1, as negative co-stimulatory molecules, are indispensable for regulating both physiological and pathological immune responses. The PD-1/PD-L1-mediated signaling pathway has been studied extensively in cancer research and has become a hotspot for biopharmaceuticals and immunotherapy. Furthermore, monoclonal antibodies to PD-1 have just been approved by the US Food and Drug Administration to treat certain types of malignancies. Recent research has unveiled a close association between the PD-1/PD-L1 system and eye diseases. This review describes the expression and physiological functions of PD-1 and its ligand in ocular tissues and summarizes the pathogenic, regulatory, and therapeutic roles of PD-1/PD-L1 system in eye diseases, including uveal melanoma, autoimmune uveitis, autoimmune dry eye, sympathetic ophthalmia, Graves' ophthalmopathy, diabetic retinopathy, herpes simplex keratitis, and trachoma, with the intent of highlighting the potential of PD-1/PD-L1 as novel therapeutic targets or biomarkers for these ocular diseases.
 ...
PMID:Exploring the role of programmed cell death protein 1 and its ligand 1 in eye diseases. 3060 20