Abstract
Animal models of glaucoma, a neurodegenerative disease affecting the retina, offer the opportunity to study candidate molecular biomarkers throughout the disease. In this work, the DBA/2J glaucomatous mouse has been used to study the systemic levels of several proteins previously identified as potential biomarkers of glaucoma, along the pre- to post-glaucomatous transition. Serum samples obtained from glaucomatous and control mice at 4, 10, and 14 months, were classified into different experimental groups according to the optic nerve damage at 14 months old. Quantifications of ten serum proteins were carried out by enzyme immunoassays. Changes in the levels of some of these proteins in the transition to glaucomatous stages were identified, highlighting the significative decrease in the concentration of complement C4a protein. Moreover, the five-protein panel consisting of complement C4a, complement factor H, ficolin-3, apolipoprotein A4, and transthyretin predicted the transition to glaucoma in 78% of cases, and to the advanced disease in 89%. Our data, although still preliminary, suggest that disease development in DBA/2J mice is associated with important molecular changes in immune response and complement system proteins and demonstrate the utility of this model in identifying, at systemic level, potential markers for the diagnosis of glaucoma.
Highlights
Glaucoma is a complex group of neurodegenerative disorders characterized by the progressive degeneration of the optic nerve, retinal ganglion cell (RGC) death and the loss of visual field [1].Global glaucoma prevalence is currently estimated in 80 million people, while the projected number of affected will increase to 118 million in 2040 [2,3]
As proof of concept the DBA/2J mouse model of glaucoma has been used considering its specific features of the human disease including age-related, elevation of intraocular pressure (IOP) with variable onset, RGC loss, and progressive optic nerve axon damage [16,18]
Ten proteins previously identified as candidate biomarkers of human glaucoma were analyzed in the serum of DBA/2J mice at pre-glaucomatous (DBA/2J_G4 ) and glaucomatous stages (DBA/2J_G10 and DBA/2J_G14 ) of the later-onset glaucoma
Summary
Glaucoma is a complex group of neurodegenerative disorders characterized by the progressive degeneration of the optic nerve, retinal ganglion cell (RGC) death and the loss of visual field [1].Global glaucoma prevalence is currently estimated in 80 million people, while the projected number of affected will increase to 118 million in 2040 [2,3]. Glaucoma is a complex group of neurodegenerative disorders characterized by the progressive degeneration of the optic nerve, retinal ganglion cell (RGC) death and the loss of visual field [1]. Pseudoexfoliation glaucoma (PEXG) are the most prevalent types of glaucoma in developed countries [4,5]. Both subtypes of glaucoma are multifactorial in origin, sharing an abnormal increase in the intraocular pressure (IOP) related with their onset. It is often clinically observed that by the time a glaucoma patient is diagnosed, he/she has already lost 35–40% of his/her RGCs [8]. There is a current need for a much more sensitive and specific method of early detection of glaucoma for an effective treatment and the improvement of its prognosis
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