Change in phospholipid species of retinal layer in traumatic optic neuropathy model

Abstract

Injured optic nerves induce death in almost all retinal ganglion cells (RGC) and cause a loss of axons. To date, we have studied injured RGC axon regeneration by using a traumatic optic nerve injury (TONI) rodent model, and we revealed that axonal regeneration is induced by the graft of an autologous peripheral nerve. The efficient approach to the regeneration of axons thus needs an environmental adjustment of RGC. However, the RGC environment induced by TONI remains unknown. Here, we analyzed female and male C57BL/6 mouse retinal tissue alterations in detail after TONI and focused on the major phospholipid species that are enriched in the whole retina. Reactive astrocyte accumulation, glia scar formation, and demyelination were observed in the injured optic nerve area, while RGC cell death, astrocyte accumulation, and Glial fibrillary acidic protein (GFAP) positive Müller cell increases were detected in the retinal layer. Furthermore, phosphatidylinositol (PI) 18:0/20:4 was localized to three nuclear layer structures: the ganglion cell layer (GCL), the inner nuclear layer (INL), and the outer nuclear layer (ONL) in control retina; however, the localization of 18:0/20:4 PI in TONI was disturbed. Meanwhile, phosphatidylserine (PS) 18:0/22:6showed that the expression was specifically in the inner plexiform layer (IPL) with similar signal intensity in both cases. Other PS species and phosphatidylethanolamine (PE) were differentially localized in the retinal layer; however, the expressions of PE including docosahexaenoic acid (DHA) were affected by TONI. These results suggest that not only GCL but also other retinal layers were influenced by TONI.

Effect of astrocyte GPER on the optic nerve inflammatory response following optic nerve injury in mice

“…Many RGCs are lost following ONC, resulting in blindness [ 63 ]. Reactive astrocyte accumulation may explain the underlying apoptotic processes in RGCs following TON [ 64 ]. Our results were similar to those of a previous study that revealed that astrocytes were activated, while their marker, GFAP, was substantially expressed on day 3 ( Supplementary Fig.…”

miR-181d-5p Protects against Retinal Ganglion Cell Death after Blunt Ocular Injury by Regulating NFIA-Medicated Astrocyte Development

“…Astrocytes have extensive proinflammatory capabilities and are regulators of inflammatory responses in the CNS [ 13 ]. Reactive astrocyte accumulation has been hypothesized to underlie RGCs apoptotic processes after TON [ 12 ]. In addition, studies have shown that excessive activation of astrocytes is detrimental to the repair of retinal ganglion cells after optic nerve injury [ 34 ].…”

“…Impairment of axonal regeneration and functional recovery results from damage to the central nervous system, enabling the transformation of naive astrocytes into reactive astrocytes and ultimately into scar-forming astrocytes [ 11 ]. Interestingly, a recent study found that the injured ON promotes astrocyte accumulation, glial scar formation, and RGCs death in the retinal layer [ 12 ]. In addition, astrocytes are emerging as central regulators of retinal ON inflammatory responses because they also have strong proinflammatory potential [ 13 ].…”

Mitochondrial Triglyceride Dysregulation in Optic Nerves Following Indirect Traumatic Optic Neuropathy

“…The impact of indirect trauma on the retina in this model has yet to be explored. Previous works on a different model of TON found that expression levels of phospholipid species were affected by traumatic optic neuropathy and may be associated with phospholipid species-specific functions [ 26 ]. Traumatic retinopathy brought on by either direct or indirect damage to the globe is referred to as commotio retinae.…”