June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Temporal analysis in Transcriptomic profile identifies immune markers and modulation of key pathways in Murine Model of Multi-Drug Resistant (MDR) Pseudomonas aeruginosa endophthalmitis
Author Affiliations & Notes
  • Joveeta Joseph Ruben
    LV Prasad Eye Institute, Hyderabad, Telangana, India
  • POONAM NAIK
    LV Prasad Eye Institute, Hyderabad, Telangana, India
  • Milind Neelkanth Naik
    LV Prasad Eye Institute, Hyderabad, Telangana, India
  • Footnotes
    Commercial Relationships   Joveeta Joseph Ruben None; POONAM NAIK None; Milind Naik None
  • Footnotes
    Support  Hyderabad Eye Research Foundation
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4275. doi:
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      Joveeta Joseph Ruben, POONAM NAIK, Milind Neelkanth Naik; Temporal analysis in Transcriptomic profile identifies immune markers and modulation of key pathways in Murine Model of Multi-Drug Resistant (MDR) Pseudomonas aeruginosa endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4275.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Increasing incidences of multidrug-resistant (MDR) P. aeruginosa (PA) causing endophthalmitis threaten our ability to manage this vision threatening condition. Understanding host-pathogen interactions is central for improving clinical outcomes. In this study, temporal dynamics of immune response in mouse model of MDR-PAendophthalmitis was investigated by transcriptome analysis.

Methods : C57BL/6 mice were infected with MDR-PA and susceptible (S-PA) and disease progression and severity was monitored at 6h and 24h post infection (p.i). The extent of retinal damage was assessed by H&E staining. Microarray analysis was performed using SuperPrint G3 Mouse Gene Expression v2 chip and the differential gene expression analysis was performed with limma package in R (v4.0.0.) /Bioconductor (v3.11). A computational pipeline then selected differentially expressed genes at both the time points and clustered them into groups with distinct temporal patterns associated with molecular functions and pathways.

Results : Histological analysis revealed significant difference in retinal architecture and vitreous infiltrates. In comparison to S-PA, MDR-PA revealed altered expression of 923 genes at 6h and 2220 genes at 24h. Further, 23% and 76% of these altered genes and their downstream interacting proteins showed time specific expression (6h and 24h respectively), indicating its association with disease progression. Adhesion proteins like Desmocollin-2,-3, Protocadherin 10, Integrin beta-3, and Cadherin-22 were upregulated during 6h, while growth factors like fgf11, fgf9, and regulator of G protein signalling were downregulated. At 24h. Lipocalin along with TNF receptor-associated factor 1 and GFAP was found to be upregulated at 24h. Histopathological changes and DEG's suggest that the magnitude of upregulation was stronger at 24h. Major clustering of genes at 24h involved in disease progression involved: inflammasome signalling, dysregulated ubiquitination, complement cascade, extracellular matrix remodelling.

Conclusions : The transcriptional differences between the two time points reveal that distinct genes contributes to disease severity and provided novel insights by extending the number of molecular determinants and functional pathways that underpin host associated damage.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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