Retinal detachment is a severe eye condition characterized by the detachment of the neurosensory retina from the retinal pigment epithelium and caused by retinal tears. Pars plana vitrectomy is the elective surgical procedure during which vitreous humor is collected. This fluid shapes the eye globe providing mechanical and nutritional support to the retina. Hence, exploring the proteome of vitreous humor isolated from subjects diagnosed with retinal detachment is supposed to help decipher the pathobiology of the disease and that of its complications, such as proliferative vitreo-retinopathy, which predispose to recurrent RD (observed in 20% of cases), a sight threatening condition. Herein, we investigated the perturbations of vitreous proteome between subjects affected by primary retinal detachment and controls by shot-gun proteomics approaches. Spectra were first searched and analyzed to identify proteome perturbations. Thereafter, starting from the hypothesis that the disease could be sustained by altered proteolytic processing of structural and non-structural elements of vitreous humor, N- and C-termini were mined to uncover endogenous proteolytic events. This search retrieved evidence of a wide repertoire of proteolytic events and proteolytic sites, either already described for proteins commonly identified also in other biological samples, or likely specific of this fluid. Comparison between the N- and C-termini landscapes and the perturbations of global proteome highlighted robust alterations of the repertoire of cleaved proteins between retinal detachment and control subjects. Strengthened by immunoblotting studies on a selection of proteins, datasets envisage that retinal detachment is characterized by unbalanced proteolysis of structural and non-structural components involved in the regulation of immune processes, proteolytic control and, in particular, angiogenesis.
