Vitreous humor in the pathologic scope: Insights from proteomic approaches

Abstract

The vitreous humor (VH) is the largest component of the eye. It is a colorless, gelatinous, highly hydrated matrix that fills the posterior segment of the eye between the lens and retina in vertebrates. In VH, a diversity of proteins that can influence retinal physiology is present, including growth factors, hormones, proteins with transporter activity, and enzymes. More importantly, the protein composition of VH has been described as being altered in a number of disease states. Therefore, attempts aiming at establishing a map of VH proteins and detecting putative biomarkers for ocular illness or protein fluctuations with putative physiologic significance were conducted over the last two decades, using proteomic approaches. Proteomic strategies often involve gel-based or LC techniques as sample fractioning approaches, subsequently coupled with MS procedures. This set of studies resulted in the proteomic characterization of a range of ocular disease samples, with particular incidence on diabetic retinopathy. However, practical therapeutic applications arising from these studies are scarce at the moment. A pertinent example of therapeutic targets arising from VH proteomics has emerged concerning vasoproliferative factors present in the vitreous, which should be involved in neovascularization and subsequent fibrovascular proliferation of the retina, in ocular disease context. Therefore, this review attempts to sum up the information acquired from the proteomic approaches to ocular disease conducted in VH samples, highlighting its clinical potential for disclosing ocular disease mechanisms and engendering pharmacological therapeutic treatments.

Systems pathology analysis identifies neurodegenerative nature of age‐related vitreoretinal interface diseases

“…Because of this close interaction, the physiological and pathological conditions of the retina are reflected directly on the protein composition of the vitreous (Monteiro et al, 2015). To obtain an in‐depth view of the vitreous humor proteome in the aging human eye, we collected and analyzed a total of 54 vitreous humor patient samples; 26 were obtained from iERM patients and 21 from MH patients.…”

“…In healthy eyes, the homeostasis of the retinal extracellular matrix (ECM) is tightly regulated. However, it is altered in ocular disorders, and this offers a means of indirectly studying the events that take place at the retina (Miller, Budoff, Prenner, & Schwarzbauer, 2017; Monteiro et al, 2015). Mass spectrometry (MS)‐based quantitative proteomics provides a means for the determination of global proteome changes at the tissue and cellular levels, enabling a molecular level characterization of the pathophysiologies of complex eye disorders.…”

Lens glutathione homeostasis: Discrepancies and gaps in knowledge standing in the way of novel therapeutic approaches

“…Soluble extracellular proteins and small molecule solutes present in the vitreous are anticipated to play a vital role in maintaining homeostasis of adjacent ocular tissues, i.e. the lens and retina(Berman, 1991; Lund-Andersen, 2003; Monteiro et al, 2015). Outstanding work from Dr. Beebe’s group suggestes another important functional mechanisms of vitreous humor, namely the regulation of molecular oxygen levels(Barton et al, 2007; Beebe et al, 1986; Filas et al, 2013; Harocopos et al, 2004; Holekamp et al, 2008; Shui et al, 2009).…”

Proteomic analysis of aqueous humor proteins associated with cataract development

“…Recently, proteomic analysis has been performed in various ocular diseases including diabetic retinopathy and cataract, which allows the simultaneous detection of a large number of proteins in specific cells, tissues or body fluids at a given time [10][11][12][13][14]. The main objective of the proteomic approach in these studies is to identify protein or peptide disease biomarkers for study of disease mechanisms, diagnosis and novel therapies.…”