Toll-Like Receptor Signaling in the Pathogenesis of Chronic Dacryocystitis: Implication of c-FOS Transcription Factor and its Downstream Effector Chemokine Genes CCL2, CCL4, CXCL3, CXCR4 with a Shift of the M1/M2 Macrophage Phenotype.

INTRODUCTION: TLRs are fundamental elements in the orchestration of the innate immune system. These receptors seem to be responsible for the inflammation and fibrosis in chronic dacryocystitis. The aim of the present study was to investigate the role of the toll-Like receptors (TLR2 and TLR4) signaling pathway and its downstream effector chemokine genes in the pathogenesis of chronic dacryocystitis. METHODS: This study was conducted on 20 patients diagnosed with chronic dacryocystitis and underwent external dacryocystorhinostomy. Estimation of gene expression of TLR2, TLR4, CCL2, CCL4, CXCL3, CXCR4, and c-FOS genes in the lacrimal sac tissues was performed together with the assessment of the inflammatory markers TNFα, IL-1ß, IFN-γ, and IL-22. Histopathological examination of the lacrimal sac walls using hematoxylin and eosin (H&E) stain, in addition to immunohistochemical staining of the CD68 and CD163 macrophage markers, was also performed. RESULTS: Our results showed that TLR2, TLR4, and c-FOS gene expressions were significantly increased in the chronic dacryocystitis group with a subsequent increase in their downstream effector chemokine genes CCL2, CCL4, and CXCL3. This up-regulation of genes was accompanied by macrophage shift of polarization toward the M1 pro-inflammatory phenotype (increased CD68 and decreased CD163 expression), leading to increased levels of the pro-inflammatory cytokines (TNF- α, IL-1ß and IFN-γ) and decreased anti-inflammatory marker IL-22 with chronic dacryocystitis. CONCLUSION: It is essential to fine-tune TLR activation through emerging therapeutic approaches. Targeting TLR signaling at the level of receptors or downstream adaptor molecules represents a new challenge for treating chronic dacryocystitis.

Normal intraocular pressure in Egyptian children and meta-analysis.

OBJECTIVE: To determine the normal intraocular pressure in a sample of Egyptian children 0-12 years of age, and compare it to that recorded in previous studies. METHODS: This is a prospective cross-sectional study, including 345 eyes. All children underwent complete history taking and ophthalmic examination. Any glaucomatous patients or glaucoma suspects were excluded. Intraocular pressure was measured using Haag Streit Perkins M2 handheld applanation tonometer under topical or general anaesthesia. Three readings were recorded for each eye and the average was calculated. Central corneal thickness was measured, using handheld pachymeter (Pachmate 2), whenever possible. RESULTS: The study included 345 eyes of 187 children (101 males and 86 females), aged 2 months to 12 years (mean: 5.69 ± 3.42 years). The recorded IOP was 5-20 mm Hg (mean: 11.5 ± 2.34 mm Hg). Central corneal thickness was 469-742 µm (mean: 564.8 ± 42.72 µm). The mean recorded intraocular pressure showed positive correlation with increased age (p = 0.026) and increased central corneal thickness (p = 0.037), with a difference of 1 mm Hg for every 100-µm change in central corneal thickness. The mean IOP was significantly lower than that recorded by most previous studies. A detailed comparative analysis is presented comparing our findings with other studies including grouped analysis, by country, ethnicity and tonometers used. CONCLUSIONS: The mean IOP in a group of normal Egyptian children was 11.5 ± 2.34 mm Hg, with positive correlation to age and central corneal thickness. This mean intraocular pressure was lower than that previously reported in any other population.