An investigation of vitreous biomarkers associated with proliferative vitreoretinopathy development

Chaudhary, Rishika (2020). An investigation of vitreous biomarkers associated with proliferative vitreoretinopathy development. University of Birmingham. M.D.

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Abstract

Introduction: During a rhegmatogenous detachment, all non-neuronal cell types undergo proliferation, resulting in PVR formation in 5-10% of cases. PVR remains the most common cause of surgical failure and poor visual prognosis1,2. Numerous surgical adjunctive agents to prevent post-operative PVR have been evaluated with limited success. Correct identification of pathogenesis and predictive biomarkers would identify therapeutic targets and allow the development of an accurate predictive model for PVR to inform management decisions.

Methods:

Design: (1), prospective observational clinical study evaluating potential predictive biomarkers of PVR on luminex cytokine analysis and metabolomic analysis of vitreous; (2), cell culture study of the fibrogenic potential of identified biomarkers on human RPE cells

Outcome measures: (1), development of PVR; (2), expression of collagen and epithelial-mesenchymal transition by RPE cells in vitro.

Results: IL-1 β and IL-7 predict PVR development. The metabolomic predictors of PVR such as 2-Hydroxyvalerate and 2-Phosphoglycerate are involved in amino acid and glutamate metabolism. IL-6, PDGF and VEGF did not have affect RPE cells fibrotic phenotype in vitro.

Conclusions: Cytokine biomarkers that predict PVR are inflammatory cytokines IL-1β and Il-7, with identified metabolomic changes consistent with these cytokine systems, therefore representing potential therapeutic targets. Inflammatory cytokines IL-6, VEGF and PDGF do not directly act on RPE cells in vitro to cause fibrosis, highlighting the important role of other retinal cells and the immune system in PVR development.

Type of Work:

Thesis (Doctorates > M.D.)

Award Type:

Doctorates > M.D.

Supervisor(s):