Early remodelling of the extracellular matrix proteins tenascin‐C and phosphacan in retina and optic nerve of an experimental autoimmune glaucoma model

Abstract

Glaucoma is characterized by the loss of retinal ganglion cells (RGCs) and optic nerve fibres. Previous studies noted fewer RGCs after immunization with ocular antigens at 28 days. It is known that changes in extracellular matrix (ECM) components conduct retina and optic nerve degeneration. Here, we focused on the remodelling of tenascin‐C and phosphacan/receptor protein tyrosine phosphatase β/ζ in an autoimmune glaucoma model. Rats were immunized with optic nerve homogenate (ONA) or S100B protein (S100). Controls received sodium chloride (Co). After 14 days, no changes in RGC number were noted in all groups. An increase in GFAP mRNA expression was observed in the S100 group, whereas no alterations were noted via immunohistochemistry in both groups. Extracellular matrix remodelling was analyzed after 3, 7, 14 and 28 days. Tenascin‐C and 473HD immunoreactivity in retinae and optic nerves was unaltered in both immunized groups at 3 days. At 7 days, tenascin‐C staining increased in both tissues in the ONA group. Also, in the optic nerves of the S100 group, an intense tenascin‐C staining could be shown. In the retina, an increased tenascin‐C expression was also observed in ONA animals via Western blot. 473HD immunoreactivity was elevated in the ONA group in both tissues and in the S100 optic nerves at 7 days. At 14 days, tenascin‐C and 473HD immunoreactivity was up‐regulated in the ONA retinae, whereas phosphacan expression was up‐regulated in both groups. We conclude that remodelling of tenascin‐C and phosphacan occurred shortly after immunization, already before RGC loss. We assume that both ECM molecules represent early indicators of neurodegeneration.

Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

“…In addition, we recently verified a transient upregulation of phosphacan in the optic nerve of an experimental autoimmune glaucoma model52. This is in agreement with our current findings, which reveal a significant upregulation of phosphacan/RPTPβ/ζ in the ischemic optic nerve.…”

Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

“…Though in DBA/2J mice no functional impairments could be observed in cells with normal morphology [ 94 ], rats with intraocular S100B injection showed a reduction in their electroretinogram amplitudes regarding the a- and b-wave after 14 days [ 29 ]. Although no electroretinogram data for systemic S100B immunization are available, rats that received a systemic ONA immunization showed a reduction in their a- and b-wave after 6 weeks [ 95 ], and S100B is a component of ONA [ 96 ]. The a-wave amplitude represents the electrical activity of the photoreceptors, and the b-wave amplitude reflects the electrical output of the inner nuclear layer.…”

Optic Nerve Degeneration after Retinal Ischemia/Reperfusion in a Rodent Model

“…qRT-PCR experiments were performed with SYBR Green I in a Light Cycler 96 (Roche Applied Science, Mannheim, Germany). Primer efficiencies of each primer set were calculated based on a dilution series of 5–125 ng cDNA (Reinehr et al, 2016b ). For normalization and relative quantification, Ct values of the house-keeping gene cyclophilin were taken into account (Table 1 ).…”