Impaired pericyte-Müller glia interaction via PDGFRβ suppression aggravates photoreceptor loss in a rodent model of light-induced retinal injury

Abstract

AIM: To investigate the involvement of pericyte-Müller glia interaction in retinal damage repair and assess the influence of suppressing the platelet-derived growth factor receptor β (PDGFRβ) signaling pathway in retinal pericytes on photoreceptor loss and Müller glial response. METHODS: Sprague-Dawley rats were exposed to intense light to induce retinal injury. Neutralizing antibody against PDGFRβ were deployed to block the signaling pathway in retinal pericytes through intravitreal injection. Retinal histology and Müller glial reaction were assessed following light injury. In vitro, normal and PDGFRβ-blocked retinal pericytes were cocultured with Müller cell line (rMC-1) to examine morphological and protein expression changes upon supplementation with light-injured supernatants of homogenized retinas (SHRs). RESULTS: PDGFRβ blockage 24h prior to intense light exposure resulted in a significant exacerbation of photoreceptor loss. The upregulation of GFAP and p-STAT3, observed after intense light exposure, was significantly inhibited in the PDGFRβ blockage group. Further upregulation of cytokines monocyte chemoattractant protein 1 (MCP-1) and interleukin-1β (IL-1β) was also observed following PDGFRβ inhibition. In the in vitro coculture system, the addition of light-injured SHRs induced pericyte deformation and upregulation of proliferating cell nuclear antigen (PCNA) expression, while Müller cells exhibited neuron-like morphology and expressed Nestin. However, PDGFRβ blockage in retinal pericytes abolished these cellular responses to light-induced damage, consistent with the in vivo PDGFRβ blockage findings. CONCLUSION: Pericyte-Müller glia interaction plays a potential role in the endogenous repair process of retinal injury. Impairment of this interaction exacerbates photoreceptor degeneration in light-induced retinal injury.

Keywords

• pericyte
• müller glia
• light-induced retinal injury
• platelet-derived growth factor receptor β
• signal pathway