McLellan, Gillian1; Adams, Grace1; Kiland, Julie1; Oikawa, Kazuya1
1University of Wisconsin-Madison
Purpose: Glaucoma is a leading cause of blindness worldwide, characterized by degeneration of retinal ganglion cell (RGC) somas and their axons in the retinal nerve fiber layer (RNFL) and optic nerve (ON). Neurofilament light chain (Nfl) is a neuronal cytoplasmic protein that is highly expressed in myelinated axons and has been proposed as a plasma biomarker in various neurodegenerative diseases in people and animals, but sparse studies in glaucoma patients have yielded conflicting results. Our goal was to determine association between circulating Nfl concentration and structural and functional markers of ON degeneration in cats with glaucoma.
Methods: Biobanked serum and plasma samples from 43 young adult cats with feline congenital glaucoma (FCG) due to LTBP2 mutation and 15 normal control cats of both sexes were assayed for Nfl (Quanterix Single molecule array [Simoa]; HD-X analyzer, [Quanterix, Billerica, MA]). Optical coherence tomography (OCT) imaging and ON axon count data provided in vivo and direct histologic ON structural metrics, respectively. Visual evoked potentials (VEP) provided a measure of ON function. Longitudinal intraocular pressure (IOP) data were also recorded. Optical coherence tomography (OCT; Heidelberg Spectralis) imaging and ON axon count data provided in vivo (RNFL thickness) and direct histologic ON structural metrics, respectively. Visual evoked potentials (VEP) provided a measure of ON function. Longitudinal intraocular pressure (IOP) data were also available for each cat.
Results: Serum Nfl concentrations were significantly higher in FCG than in normal cats (p=0.0009), with no significant difference between sexes, and no association with age in this young cohort. Serum Nfl concentration showed a weak negative correlation with ON axon count and VEP amplitude (Pearson r = -0.213 and -0.219, respectively) and modest positive correlation with VEP latency (r=0.286 and maximum IOP value measured in the worst affected eye (r= 0.348) Serum and plasma Nfl values were highly correlated (r2 =0.996) and could be interchangeable in a clinical setting.
Conclusions: Circulating serum Nfl concentrations are elevated in glaucoma but are only modestly associated with direct measures of ON neurodegeneration in this feline glaucoma model, which may limit clinical application as a fluid biomarker in this disease.
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