Retinal microglia signaling affects Müller cell behavior in the zebrafish following laser injury induction

Federica Maria Conedera1,2,3, Ana Maria Quintela Pousa1,2, Nadia Mercader4

  • 1Department of Ophthalmology, University Hospital of Bern, University of Bern, Bern, Switzerland.

Glia
|February 23, 2019
PubMed

Insights

Microglia and Müller cells are crucial for retinal repair in zebrafish. Depleting microglia impairs regeneration, highlighting their vital role in Müller cell responses and unlocking retinal regenerative potential.

Area of Science:

  • Neuroscience
  • Ophthalmology
  • Immunology

Background:

  • Microglia, the central nervous system's resident macrophages, interact with Müller cells, the primary glial cells in the retina.
  • These bidirectional microglia-Müller cell interactions influence retinal injury responses, with both beneficial and detrimental outcomes reported.
  • The specific role of Müller cell reactivity and survival in the absence of immune cells post-injury in adult zebrafish remains underexplored.

Purpose of the Study:

  • To investigate Müller cell behavior and retinal regeneration in adult zebrafish following focal injury and immune cell depletion.
  • To elucidate the necessity of microglia and macrophages for Müller cell reactivity and regenerative processes in the injured retina.

Main Methods:

  • Developed a focal retinal injury model in adult zebrafish using diode laser to damage photoreceptors.
  • Employed pharmacological agents: PLX3397 for macrophage-microglia depletion and clodronate liposomes for selective peripheral macrophage elimination.
  • Assessed Müller cell responses by analyzing glial fibrillary acidic protein (GFAP), Phospho-p44/42 MAPK (Erk1/2), and PCNA expression, alongside cell cycle reentry.

Main Results:

  • PLX3397-induced depletion of microglia and macrophages significantly hindered retinal regeneration, an effect reversed upon microglial repopulation.
  • Selective elimination of peripheral macrophages did not alter the kinetics of retinal regeneration.
  • Absence of retinal microglia and macrophages led to dysregulated Müller cell behavior, characterized by suppressed GFAP and Erk1/2 upregulation and unaffected cell cycle reentry post-injury.

Conclusions:

  • Microglia-Müller cell signaling is essential for activating Müller cell regenerative potential in the damaged retina.
  • Microglia play a pivotal role in orchestrating Müller cell responses necessary for effective retinal repair in zebrafish.
  • Targeting microglia-Müller cell interactions could be a key strategy for enhancing retinal regeneration.

Related Concept Videos

What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
130.3K
Cell-surface Signaling01:21

Cell-surface Signaling

Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
54.3K
Bacterial Signaling01:30

Bacterial Signaling

Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
40.6K
Overview of Cell Signaling01:23

Overview of Cell Signaling

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate with the environment.
Cells respond to many types of information, often through receptor proteins positioned on the membrane. For example, skin cells respond to and transmit touch...
24.6K
Cell Signaling in Plants01:25

Cell Signaling in Plants

Plant cells communicate to coordinate their cycle of growth, flowering and fruiting, and activities in roots, shoots, and leaves in response to the changing environmental conditions. Plant signaling is distinct from animal signaling. Plants primarily utilize enzyme-linked receptors, whereas the largest class of cell-surface receptors in animals are G-protein coupled receptors (GPCRs). Unlike animals, receptor tyrosine kinases are rare in plants. Instead, plants have a diverse class of...
6.2K
What is Behavior?00:54

What is Behavior?

Behaviors are actions that an organism engages in—they can be related to finding food, reproducing, defending against threats, and many other possible actions. Behaviors include activities related to the environment around the animal—such as migration—as well as social interactions within a species or population. Many behaviors involve motor output—that is, muscle movements—while others involve less visible actions, such as learning.
10.3K