A Biomarker for Retinal Degeneration: Vitreous Body Neurofilaments

Abstract

Purpose: : Biomarkers are an attractive tool for quantifying neurodegeneration. Neurofilaments can be used to specifically measure neuro–axonal loss because they are generally not expressed in other cell–types. The main aim of this study was to investigate whether the phosphorylated form of the neurofilament heavy chain (NfH^SMI35), an important biomarker for axonal degeneration, could be measured from a fluid compartment of the eye.

Methods: : Aqueous humour samples were collected from glaucoma patients who underwent routine trabeculectomy for primary open–angle glaucoma (POAG) or pseudoexfoliation open–angle glaucoma (PEXG). Vitreous humour samples were collected from 14 patients who underwent vitrectomy for retinal detachment (RD) and macular hole (MH) surgery. The control group consisted of patients in whom we did not expect to find any axonal pathology. Two of the control patients suffered from epiretinal gliosis and one underwent vitrectomy during cataract surgery due to a nanophthalmic eye. A previously–described ELISA technique was used to quantify NfH levels.

Results: : Vitreous body homogenate NfH^SMI35 levels were detectable in all samples of vitreous body homogenate. There was no correlation between the NfH^SMI35 levels and the patients’ age (Spearman’s R=–0.29, p=0.31). The highest value observed in the control group was 0.47 ng/mL NfH^SMI35 . Comparable NfH^SMI35 levels were observed in patients with MH (0.03 to 0.34 ng/mL). For patients with RD a bimodal distribution was observed with one group having NfH^SMI35 levels of 0.06 to 0.23 ng/mL and the other one achieving concentrations of 0.83 to 1.49 ng/mL. Neurofilament levels could not be detected in any of the anterior chamber fluid samples.

Conclusions: : This study is the first to show that NfH^SMI35 can be quantified from the vitreous body, but not from the anterior chamber fluid in humans. We hypothesize that high vitreous body NfH^SMI35 levels in some RD patients suggests considerable axonal loss

Keywords: vitreous • retina: neurochemistry • degenerations/dystrophies