Osteopontin/Secreted Phosphoprotein 1 is Reduced in the Human Retina and Optic Nerve During Glaucoma Pathogenesis

Secreted phosphoprotein 1 (SPP1) has emerged as an important protein in neurodegenerative disease. In glaucoma, a neurodegenerative disease where retinal ganglion cells degenerate, this is particularly related to its expression in resistant subtypes of retinal ganglion cell. Overexpression of SPP1 provides neuroprotection. However, whether SPP1 expression profiles in the rodent match human glaucoma has yet to be determined and is important in understanding the translational relevance of SPP1-based therapies. A cohort of highly preserved and well-characterized human donor retina was used to perform antibody labeling and quantification of SPP1 in human retina and optic nerve and compare this to RNA sequencing data. It was demonstrated that SPP1 expression is highest in glia cells, but antibody labeling demonstrates its presence throughout the retina. In human glaucoma, SPP1 labeling is reduced in the ganglion cell complex (representing retinal ganglion cell axons, somas, and dendrites) and optic nerve (retinal ganglion cell axons). These data support the relevance of SPP1 as a target for neuroprotection in human glaucoma.