Matrix-metalloproteinase expression and gelatinase activity in the avian retina and their influence on Müller glia proliferation
| Autor: | Sydney Blum, Seth Blackshaw, Andy J. Fischer, Joshua Zent, Jennifer L. Leight, Thanh Hoang, Warren A. Campbell, Jessica L Weist, Ameya Deshmukh, Ninoshka Mendonca, Levi Todd |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gelatinases MMP2 Ependymoglial Cells Matrix metalloproteinase Retina Article Extracellular matrix 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience medicine Gelatinase Animals Retinal regeneration Cell Proliferation Chemistry Stem Cells Cell migration Cellular Reprogramming Cell biology Nerve Regeneration 030104 developmental biology medicine.anatomical_structure Neurology Matrix Metalloproteinase 2 sense organs Muller glia Chickens 030217 neurology & neurosurgery |
| Zdroj: | Exp Neurol |
| ISSN: | 1090-2430 |
| Popis: | Gelatinases are a class of matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) to regulate intercellular signaling and cell migration. Gelatinase activity is tightly regulated via proteolytic activation and through the expression of tissue inhibitors of matrix metalloproteinases (TIMPs). Gelatinase activity has been implicated in retinal pathophysiology in different animal models and human disease. However, the role of gelatinases in retinal regeneration remains uncertain. In this study we investigated the dynamic changes in gelatinase activity in response to excitotoxic damage and how this enzymatic activity influenced the formation of Müller glia progenitor cells (MGPCs) in the avian retina. This study used hydrogels containing a gelatinase-degradable fluorescent peptide to measure gelatinase activity in vitro and dye quenched gelatin to localize enzymatic activity in situ. These data were corroborated by using single cell RNA sequencing (scRNA-seq). Gelatinase mRNA, specifically MMP2, was detected in oligodendrocytes and non-astrocytic inner retinal glia. Total retinal gelatinase activity was reduced following NMDA-treatment, and sustained inhibition of MMP2 prior to damage or growth factor treatment increased the formation of proliferating MGPCs and c-fos signaling. We observed that microglia, Müller glia (MG), and Nonastrocytic Inner Retinal Glia were involved in regulating changes in gelatinase activity through TIMP2 and TIMP3. Collectively, these findings implicate MMP2 in reprogramming of Muller glia into MGPCs. |
| Databáze: | OpenAIRE |
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