Review
Glia–neuron interactions in the mammalian retina

https://doi.org/10.1016/j.preteyeres.2015.06.003Get rights and content
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Abstract

The mammalian retina provides an excellent opportunity to study glia–neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K+ uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.

Keywords

Retina
Neurons
Glial cells
Astrocytes
Müller glia
Microglia
Macrophages
Retinal ganglion cells
Photoreceptors
Glaucoma
Retinitis pigmentosa
Neuroprotection
Neurotrophins
Plasticity
Integrins
Extracellular matrix

List of abbreviations

AAV
adeno-associated virus
Ach
acetylcholine
AGA
amadori-glycated albumin
AGE
advanced glycation end-products
AhR
aryl hydrocarbon receptor
AKT
protein kinase B
AMD
age-related macular degeneration
AP-1
activating protein-1
APC
antigen-presenting cells
Apo
apolipoprotein
AQP
aquaporin
ASCL1
achaete-scute family bHLH transcription factor 1
Atoh7
atonal homolog 7
ATP
adenosine triphosphate
BBB
blood–brain barrier
Bcl-2
B-cell lymphoma 2
BDNF
brain-derived neurotrophic factor
bFGF
basic fibroblast growth factor
BMP
bone morphogenetic protein
BV
blood vessel
CaMKII
Ca2+/calmodulin-dependent protein kinase
Car2
carbonic anhydrase II
CCL2
monocyte Chemotactic Protein-1
CCR2
C–C chemokine receptor type 2
CD45
cluster of differentiation 45
Cdc14A
cell division cycle 14A
Cdk10
cyclin-dependent kinase 10
Ch
choroid
ChAT
choline acetyltransferase
CHX10
Ceh-10 homeodomain-containing homolog
CNS
central nervous system
CNTF
ciliary neurotrophic factor
CNV
choroidal neovascularisation
CRALBP
cellular retinaldehyde-binding protein C
CREB
cAMP response element-binding protein
CSF1R
colony stimulating factor 1 receptor
CSPG
chondroitin sulphate proteoglycans
CTGF
connective tissue growth factor
CX3CL1
chemokine (C-X3-C Motif) Ligand 1
CX3CR1
CX3C chemokine receptor 1
DAPI
4′,6-diamidino-2-phenylindole
DAPT
γ-Secretase inhibitor
DHA
docosahexaenoic acid
DKK3
Dickkopf-related protein 3
DR
diabetic retinopathy
EAAT
excitatory amino acid transporter
ECM
extracellular matrix
ED-1
monoclonal antibody against glycoprotein CD68
EGF
epidermal growth factor
EMV
extracellular membrane microvesicles
ESMV
embryonic stem cells microvesicles
FG
fluorogold
FGF
fibroblast growth factor
FKN
fraktalkine
G6P
Glucose-6-Phosphate
GABA
γ-aminobutyric acid
gadd45b
growth Arrest And DNA-Damage-Inducible Beta
GCL
ganglion cell layer
GDNF
glia-derived neurotrophic factor
GFAP
glial fibrillary acidic protein
GFP
green fluorescent protein
GK
Goto Kakizaki
GLAST
glutamate-aspartate transporter
GLT1
glial Glutamate Transporter 1
Gpc
glypican
GS
glutamine synthetase
hMGSC
human Müller glia stem cells
HSPG
heparin sulphate proteoglycan
IBA1
ionized calcium-binding adapter molecule 1
IF
intermediate filaments
IFN
interferon
IGF
insulin-like growth factor
IL
interleukin
ILM
inner limiting membrane
INL
inner nuclear layer
IOP
intraocular pressure
IP3R2
IP3 receptor type 2
IPL
inner plexiform layer
JNK
C-Jun N-terminal kinase
Kir
inwardly rectifying potassium channels
LCA
Leber congenital amaurosis
LDL
low-density lipoproteins
LGN
lateral geniculate nucleus
LIF
leukaemia inhibitory factor
MAPK
mitogen-activated protein kinases
Mash1
mammalian achaete-scute homolog-1
MCP1
monocyte chemoattractant protein-1
Megf10
multiple epidermal growth factor-like domains protein 10
Mertk
tyrosine-protein kinase Mer
MHC
major histocompatibility complex
MMP
matrix metalloproteinases
mTOR
mechanistic target of rapamycin
NAD
nicotine adenine dinucleotide
NADPH
nicotinamide adenine dinucleotide phosphate
NF
neurofilaments
NFL
nerve fibre layer
NFκ&Bgr
uclear factor kappa-light-chain-enhancer of activated B cells
NGF
nerve growth factor
NMDA
N-Methyl-d-aspartate
NO
nitric oxide
NPD1
neuroprotectin D1
NPPB
5-nitro-2-[(3-phenylpropyl)amino]benzoic acid
NV
neovascularisation
OIR
oxygen-induced retinopathy
OLM
outer limiting membrane
ON
optic nerve
ONL
outer nuclear layer
OPC
oligodendrocyte precursor cells
OPL
outer plexiform layer
OPN
osteopontin
OS
outer segment layer
P2Y
metabotropic purinergic
Pax6
paired box 6
PCAG
primary closed-angle glaucoma
PCG
primary congenital glaucoma
PE
pigment epithelium
PEDF
pigment epithelium-derived factor
PI3K
phosphatidylinositol-4,5-bisphosphate 3-kinase
PKB
protein kinase B
PLC
phospholipase C
POAG
primary open angle glaucoma
PSD95
postsynaptic density protein 95
rd10
retinal degeneration 10
RFP
red fluorescent protein
RGC
retinal ganglion cells
RGCL
retinal ganglion cells layer
RNA
ribonucleic acid
ROS
reactive oxygen species
RP
retinitis pigmentosa
RPE
retinal pigment epithelium
RT-PCR
reverse transcription polymerase chain reaction
RVD
regulatory Volume Decrease
SELDI-TOF
surface-enhanced laser desorption ionization-time of flight
SNAP25
synaptosomal-associated protein 25
SP-A
surfactant protein A
Spbc25
spindle pole body component 25
STAT
signal transducers and activators of transcription transient
STZ
streptozotozin
TAK1
transforming growth factor β-activated kinase 1
TCA
tricarboxylic acid cycle
TGF&Bgr
transforming growth factor beta
Thy-1
thymocyte antigen 1
TN-C
tenascin C
TNF
tumour necrosis factor
TRK&Bgr
tropomyosin receptor kinase B
uPA
urinary-type plasminogen activator
VEGF
vascular endothelial growth factor
Vim
vimentin
WNT
Wingless-Type MMTV integration site family

Cited by (0)

1

Each co-author contributed equally (20%) to this article.

2

www.ehu.es/GOBE.