Toll-Like Receptor Expression and Activation in Mice with Experimental Dry Eye

Abstract

DTS modulates the expression of TLR and CRAMP and topical application of TLR agonists in EDE mice resulted in corneal epithelial loss and thinning. These results suggest that TLRs are involved in DTS inflammation.

Desiccating Stress–Induced Chemokine Expression in the Epithelium Is Dependent on Upregulation of NKG2D/RAE-1 and Release of IFN-γ in Experimental Dry Eye

“…One link between cellular stress and NK cell activation is increased RAE-1 expression via Toll-like receptor (TLR) stimulation (37). TLRs 2-4 and 9 are increased in the cornea and conjunctiva epithelial cells of dry eye mice (38). In our model, we observed an increase in RAE-1 ligands and did not detect the related MULT1 or CD99 ligand.…”

Monitoring of Strain-Dependent Responsiveness to TLR Activation in the Mouse Anterior Segment Using SD-OCT

“…Previously, SD-OCT has been used to quantify age-related and TLR ligand-mediated corneal thickness changes in mice [27][28][29] and to assess corneal reflectivity during a sterile wound healing response. 30 At baseline, the adult BALB/c cornea is approximately 10% thicker than the C57BL/6 cornea.…”

Age-related Defects in Ocular and Nasal Mucosal Immune System and the Immunopathology of Dry Eye Disease

“…17–22 An expansion of CD4 + CD25 (low) GITR (+) T reg cells has been detected in inflamed tissues of the salivary glands of Sjögren syndrome patients. 53,54 This expansion may represent a regulatory attempt to reduce excessive inflammation.…”

“…9–16 When the integrity of one of these ocular surface compartments is disrupted, this may lead to DED, thus compromising the normal function of the visual system. Two interconnected external and internal mechanisms cause DED 17–22 : (1) an age-related decrease in tear production and/or an increase in tear evaporation that triggers a sustained ocular surface inflammation, which in the elderly can lead to blindness from corneal epithelial barrier disruption, ulceration, and scarring 23–26 and (2) an age-related inflammation of the surface of the eye, triggered by yet-to-be-determined immunopathological mechanisms, independent of tear deficiency. This inflammation compromises the function of lacrimal and meibomian glands, which reduces tear film stability and osmolarity, leading to inflammatory DED.…”

“…For more details on other aspects of DED, such as disruption of homeostatic mechanisms in DED, anti-inflammatory therapy in DED, mucosal autoimmune disease and DED, role of Toll-like receptors in DED, the prevalence and risk factors of DED in the elderly, and relevance of animal models for the research into the immunophysiological processes regulating the functions of the lacrimal gland, we direct the readers to the following excellent reviews by Dana et al, 16,38 Pflugfelder et al, 13 De Paiva et al, 13 McDermott et al, 17,21 Perez et al, 1,39–41 and Mercheff et al 42–44 …”