Vitreous proteomic analysis of proliferative vitreoretinopathy

Abstract

Proliferative vitreoretinopathy (PVR) is the most common cause of anatomic failure in retinal detachment surgery. To understand the molecular mechanisms, vitreous proteomes of patients with PVR were investigated by two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry. Vitreous samples of moderate PVR (grade B), and severe PVR (grade C or D) were aspirated during pars plana vitrectomy before infusion. In the current study, 129, 97 and 137 proteins were identified in vitreous of normal control, moderate and severe PVR, respectively. In PVR vitreous samples, complement components, serine proteinase inhibitors, and extracellular proteins were up-regulated or appeared, while normal cytoskeleton and metabolism proteins were down-regulated or disappeared. It was noteworthy that the proteins involved in transcription and translation regulation increased in vitreous with PVR. Among 102 PVR-specific proteins, kininogen 1 was specifically detected in both vitreous and the corresponding serum. Therefore, it can be concluded that PVR is a complicated pathology process with great amount of proteins involved in metabolism dysfunction, immune reactions, and cytoskeleton remolding. Kininogen 1 may be a candidate biomarker of PVR. Further investigations of these special proteins will provide additional targets for treatment or prevention of ocular proliferative diseases.

Receptor mediated disruption of retinal pigment epithelium function in acute glycated-albumin exposure

“…Although the formation of AGEs is a natural process that occurs with aging and nearly all proteins in the body carry some burden of glycation (Monnier et al, 1992), the rate of AGE formation is accelerated in diabetic conditions due to persistent hyperglycemia and oxidative stress (Baynes and Thorpe, 1999). Several studies in the eye have shown an association between the level of AGE products in the vitreous and the clinical progression of DME (Stitt et al, 1998; Yokoi et al, 2005; Yu et al, 2008). To control appropriate responses, cells have a pattern recognition receptor (RAGE) to detect the levels of AGEs in the environment.…”

The upregulation of zinc finger protein 670 and prostaglandin D2 synthase in proliferative vitreoretinopathy

“…This phenomenon has been reported in proliferative diabetic retinopathy and PVR [21,22]. Once retinal detachment occurs, the initial breakdown of the blood-retina barrier contributes part of the increased proteins of the vitreous in PVR [23][24][25].…”

Enhanced expression of the complement factor H mRNA in proliferating human RPE cells

“…Recently, an increased expression of fI was detected in the vitreous of patients with proliferative diabetic retinopathy (PDR) [10], and the complement factors B, H, and I were detected in the PVR vitreous humor [35]. Whereas the authors conclude that their study provides proof of the destruction of blood retina barriers in the PVR samples because many common serum proteins, such as hemopexin, apolipoprotein A-I, A-II, H, and complement components significantly increased in PVR vitreous humor, our finding of a clear expression of fH and fH in epiretinal membranes identified RPE cells as an additional important source of complement regulatory proteins in these membranes.…”