Retina Development Flashcards
When does eye development begin?
week 4 –> 8 years post natal
neural tissues (forebrain) forms
retina, RPE, iris, ciliary body
surface ectoderm forms
lens, eyelids, cornea
neural crest forms
cornea, ciliary body
mesenchyme forms
sclera, blood vessels
5 parts of neural tube
telencephalon diencephalon mesencephalon metencephalon myelencephalon
Eyes are outgrowings of?
the diencephalon - optic vesicles
optic vesicles reach what and what happens?
surface ecoderm - induces lens placode
optic cup folds - bilayer optic cup
posterior region of optic cup
optic stalk - blood vessels and axons
lens placode invaginates to form what?
lens vesicle
what does lens placode lose contact with?
surface epithelium
2 parts of optic cup
retina and RPE
what does lens vesicle make?
lens
what induces formation of cornea?
signals from lens
spemann and Lewis, 1900
amphibians - contact of optic nesicle with surface ectoderm - form lens
remove optic vesicle = no lens placode
Later optic vesicle/lens induction experiments
lens like structure can form
differences in timing of inductive events between species
Can all ectoderm form a lens? why?
no - at gastrulation head ectoderm bias towards lens fate
optic vesicle transplanted to trunk
no lens
lens signalling back to optic vesicle
lens induce expression in distal optic cup of genes - Chx10, Lhx2 for neural retina development
dissect of epithelium or rotate optic vesicle - retina genes
no expression as no lens
retina genes where normally RPE
signals from where pattern optic cup?
lens and extraocular mesenchyme
extraocular mesenchyme - RPE genes
upregulate
where is pax 6 expressed?
widely in developing eye - optic cup and lens vesicle
master regulator of eye development
pax6
mouse - pax 6
\+/- = microphthalmia - small eyes -/- = no eyes
Pax 6 +/- humans
no iris, cataract, glaucoma
other genes essential for eye development
Rx - retinal homeobox
six3
genes eye development - early distribution
pax 6, rx and six 3 continuous across early neural plate
single eye field
What splits eyefield in two?
shh in midline of neural tube
what does shh activate?
expression of genes required for optic stalk development eg pax 2
what does shh repress?
expression of genes required for optic vesicle development eg pax 6
pax 6 and pax 2
mutual repressors
cyc -/- or shh -/-
pax 6 not repressed at midline - no activation of pax2
form single large optic cup
increased shh in midline
increased repression pax 6 and increased activation pax 2
smaller eye field
cyclopia in humans
rare
disrupt shh signalling
associated with cranial defects
lose midline structures
what is nasal/temporal and dorsal/ventral patterning of retina needed for?
visual function - green cones in dorsal and blue cones ventral
mapping retina onto visual targets - positional identity
what cells relay visual info from eye to brain?
RGC
primary target of RGC
amphibians = tectum
humans - LGN, some to superior colliculus
dorsal and ventral RGC axons to tectum
dorsal - lateral
ventral - medial
nasal and temporal RGC axons to tectum
nasal posterior
temporal - anterior
transcription factors imposing n/t and d/v specificty of optic cup
nasal - Foxg1 and SOHO1
temporal - Foxd1
dorsal - Tbx5
ventral - Vax2
What does vax 2 in ventral retina induce expression of?
EPHBs
Express EPHB in dorsal retina also or KO
dorsal = ventral and dorsal RGC map medially KO = both map laterally
retina cell types
6 neuronal cell types and muller glia
rods, cones, horizontal, bipolar, amacrine, RGC
Retinal progenitor cell fate
became all major types but biased
generation of retinal cell types
stereotypical sequence
ganglion cells first, amacrine, horizontal, cones, rods, bipolar, muller glia
waves of retinal neurogenesis
central - peripheral
ciliary margin
far peripheral retina
neurogenesis continues here in lower vertebrates throughout life - stem cells?
asymmetric and symmetric division of progenitor cells
symmetric = 2 progenitor or undifferentiated cell asymmetric = 1 of each
where are RGC found?
inner most surface of retina
where do progenitor cells divide?
adjacent to RPE
what happens to progenitors that differentiate as RGC?
basal process to vitreal surface
nucleus migrates
axon extends into OFL
break attachment of apical surface
what triggers the initial central patch of differentiated RGCs?
FGFs
evidence for FGF - central RGC
FGF expressed in central retina/optic stalk before neuogenesis
block FGF inhibits neurogenesis
what drives RGC differentitation in fish?
shh
RGC differentiation in fish
wave of shh - self propagating
disrupt shh signal = neurogenesis initiates but fails to spread normally
commitment to RGC fate - important
notch/delta signalling - premature differentiation, overproduction RGC
Atho7 - no RGC
Islet2 - born but fail to differentiate and die
retinal cell types - bias
eg VC1.1 -ve = cones
+ve = amacrine/horz
+ve then -ve = rods
generation of retinal cell types
cannot go back or skip a step
controlled by transcription factors
environment
