Proteomic analysis of vitreous humour of eyes with diabetic macular oedema: a systematic review

The pathophysiology of diabetic macular oedema (DME) remains poorly understood. Proteomic analysis of the vitreous using mass spectrometry (MS) can potentially identify proteins of pathophysiological importance. In this systematic review, we summarize the available evidence on protein changes in DME detected by MS. We systematically searched 13 literature databases on 19 September 2021. Eligible studies were defined as those using samples from human eyes with DME analysed with MS. Two authors assessed the studies for eligibility, extracted data and evaluated risk of bias independently. Six eligible studies were identified. All were designed in a cross-sectional fashion comparing results to either a non-diabetic control group or a control group without DME. A total of 62 eyes from 60 patients contributed as study group and 48 eyes from 48 patients served as control group. Proteomic analyses revealed significant differences in the vitreous protein levels in patients with DME when compared with controls. Three studies or more identified increased contents of apolipoprotein A-I, apolipoprotein A-II, apolipoprotein A-IV, apolipoprotein C-III, gelsolin, pigment epithelium-derived factor, serum albumin, transthyretin, vitamin D-binding protein in DME. Two studies found increased levels of complement factors B and C3. Protein changes reproduced across the studies suggested that DME was associated with retinal lipid accumulation, angiogenesis, retinal protective mechanisms, inflammation and complement activation. Proteome studies support the multifactorial pathogenesis of DME as proteins with highly different biological functions are regulated in DME. An important number of proteins differ, provide pathophysiological insight and suggest the direction for future research.