Doxycycline in the Management of Pseudomonas Corneal Melting

McElvanney, A M

doi:10.1097/01.icl.0000086490.38331.58

Cited by 37 publications

(23 citation statements)

References 30 publications

(28 reference statements)

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“…Other MMPs also had highly upregulated gene expression in both BK and FK, including MMP10, blockade of which improves corneal epithelial healing in diabetic corneas (Saghizadeh et al, 2013). Pharmacological inhibition of MMPs with tetracyclines has shown some success toward halting corneal perforation in both animal models and human MK, and thus may prove to be a potential therapeutic target (Levy and Katz, 1990; McElvanney, 2003). …”

Section: Discussionmentioning

confidence: 99%

Persistence of Innate Immune Pathways in Late Stage Human Bacterial and Fungal Keratitis: Results from a Comparative Transcriptome Analysis

Chidambaram

Kannambath

Srikanthi

et al. 2017

Front. Cell. Infect. Microbiol.

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Microbial keratitis (MK) is a major cause of blindness worldwide. Despite adequate antimicrobial treatment, tissue damage can ensue. We compared the human corneal transcriptional profile in late stage MK to normal corneal tissue to identify pathways involved in pathogenesis. Total RNA from MK tissue and normal cadaver corneas was used to determine transcriptome profiles with Illumina HumanHT-12 v4 beadchips. We performed differential expression and network analysis of genes in bacterial keratitis (BK) and fungal keratitis (FK) compared with control (C) samples. Results were validated by RTqPCR for 45 genes in an independent series of 183 MK patients. For the microarray transcriptome analysis, 27 samples were used: 12 controls, 7 BK culture positive for Streptococcus pneumoniae (n = 6), Pseudomonas aeruginosa (n = 1), and 8 FK, culture positive for Fusarium sp. (n = 5), Aspergillus sp. (n = 2), or Lasiodiplodia sp. (n = 1). There were 185 unique differentially expressed genes in BK, 50 in FK, and 339 common to both [i.e., genes with fold-change (FC) < −4 or ≥4 and false discovery rate (FDR) adjusted P < 0.05]. MMP9 had the highest FC in BK (91 FC, adj p = 3.64 E-12) and FK (FC 64, adj. p = 6.10 E-11), along with other MMPs (MMP1, MMP7, MMP10, MMP12), pro-inflammatory cytokines (IL1B, TNF), and PRRs (TLR2, TLR4). HIF1A and its induced genes were upregulated uniquely in BK. Immune/defense response and extracellular matrix terms were the most enriched Gene Ontology terms in both BK and FK. In the network analysis, chemokines were prominent for FK, and actin filament reorganization for BK. Microarray and RTqPCR results were highly correlated for the same samples tested with both assays, and with the larger RTqPCR series. In conclusion, we found a great deal of overlap in the gene expression profile of late stage BK and FK, however genes unique to fungal infection highlighted a corneal epithelial wound healing response and for bacterial infection the prominence of HIF1A-induced genes. These sets of genes may provide new targets for future research into therapeutic agents.

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Section: Discussionmentioning

confidence: 99%

Persistence of Innate Immune Pathways in Late Stage Human Bacterial and Fungal Keratitis: Results from a Comparative Transcriptome Analysis

Chidambaram

Kannambath

Srikanthi

et al. 2017

Front. Cell. Infect. Microbiol.

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“…Matrix metalloproteinases (MMPs) is one group of proteases, which include collagenases, gelatinases, and stromelysins. [3233] Inhibition of MMPs may be helpful in the prevention of stromal destruction. Proposed MMP inhibitors which have been proposed for use in microbial keratitis include tetracyclines, acetylcysteine, ascorbate, and sodium ethylenediaminetetraacetic acid.…”

Section: Matrix Metalloproteinases Inhibitorsmentioning

confidence: 99%

“…McElvanney[33] reported two cases of culture-proven pseudomonas bacterial keratitis treated oral doxycycline 100 mg twice daily, in addition to topical ofloxacin 0.3% and ceftazidime 5%. He found that stabilization of corneal melting occurred, but this report offers little or nothing in regard to evidence of the benefit of doxycycline.…”

Section: Matrix Metalloproteinases Inhibitorsmentioning

confidence: 99%

Adjunctive therapies for bacterial keratitis

Dakhil

Stone

Gritz

2017

Middle East Afr J Ophthalmol

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“…The use of anti‐collagenase treatment, such as medroxyprogesterone (MPG) may have a protective role or serve to reduce the severity of the condition. Oral tetracycline also prevents corneal melting . This form of treatment has been used in several studies following corneal graft procedures.…”

Section: Treatmentmentioning

confidence: 99%