Differential Response of Müller Cells and Microglia in a Mouse Retinal Detachment Model and Its Implications in Detached and Non-Detached Regions.

Seung-Hee Lee,In-Beom Kim,Yong-Soo Park,Sun-Sook Paik

doi:10.3390/cells10081972

Abstract

Retinal detachment (RD) is a sight-threatening condition, leading to photoreceptor cell death; however, only a few studies provide insight into its effects on the entire retinal region. We examined the spatiotemporal changes in glial responses in a mouse RD model. In electroretinography, a- and b-waves were reduced in a time-dependent manner. Hematoxylin and eosin staining revealed a gradual decrease in the outer nuclear layer throughout the retinal region. Terminal deoxynucleotidyltransferase dUTP nick end labeling (TUNEL) assay showed that TUNEL-positive photoreceptors increased 5 days after RD and decreased by 14 days. Glial response was evaluated by immunohistochemistry using antibodies against glial fibrillary acidic protein (GFAP, Müller glial marker) and Iba-1 (microglial marker) and osteopontin (OPN, activated microglial marker). GFAP immunoreactivity increased after 7 days in complete RD, and was retained for 14 days. OPN expression increased in microglial cells 3–7 days after RD, and decreased by 14 days in the detached and border regions. Although OPN was not expressed in the intact region, morphologically activated microglial cells were observed. These retinal glial cell responses and photoreceptor degeneration in the border and intact regions suggest that the effects of RD in the border and intact retinal regions need to be understood further.

Highlights

Retinal detachment (RD) is a sight-threatening condition, in which the outer segments of the photoreceptors physically separate from the underlying retinal pigment epithelium (RPE), which acts as a photoreceptor nourishment source
Rhegmatogenous detachment is the most common cause of RD, which is characterized by retinal tear-inducing vitreous penetration under the retina [1], while tractional detachment and exudative detachment are rare types of RD caused by a complication of various retinal disorders, including age-related macular degeneration (AMD) [2] and diabetic retinopathy (DR) [3]
We established and characterized animal retinal degeneration models, such as N-methyl-nitrosourea (MNU)-induced rat model [15] and a blue light-emitting diode (LED)-induced mouse model [16]. In these retinal degeneration models, we found that microglial cells and Müller glial cells were activated, and an increase in pro-inflammatory cytokines was seen [15,16,17,18,19], suggesting that inflammation is a critical mechanism in its pathogenesis

Summary

Introduction

Retinal detachment (RD) is a sight-threatening condition, in which the outer segments of the photoreceptors physically separate from the underlying retinal pigment epithelium (RPE), which acts as a photoreceptor nourishment source. Photoreceptor cell death continues during RD, causing progressive visual impairment. RD can be classified into three types: rhegmatogenous, tractional, and exudative. Rhegmatogenous detachment is the most common cause of RD, which is characterized by retinal tear-inducing vitreous penetration under the retina [1], while tractional detachment and exudative detachment are rare types of RD caused by a complication of various retinal disorders, including age-related macular degeneration (AMD) [2] and diabetic retinopathy (DR) [3]. Progressive photoreceptor cell death occurs in multiple ways in the detached region of the retina, including via apoptosis [6,7], necroptosis [8,9,10], and autophagy [11,12]

Objectives

Methods

Results

Conclusion