Ocular retardation (or) in the mouse.
Ocular retardation (or) in the mouse.
Ocular retardation (or) in the mouse.
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Volume 17<br />
Number 5 Rep<strong>or</strong>ts 469<br />
Fig. 1. Sagittal sections of eyes at 11.0 days' gestation. A, Eye ot <strong>or</strong> 1 mutant, vessels nave<br />
entered optic cup through ret<strong>in</strong>al p<strong>or</strong>tion of optic fissure. There are no necrotic foci <strong>in</strong> <strong>the</strong><br />
ret<strong>in</strong>al rudiment. The lens pit is f<strong>or</strong>m<strong>in</strong>g n<strong>or</strong>mally. (x235.) B, N<strong>or</strong>mal eye. Note zones of<br />
necrosis <strong>in</strong> d<strong>or</strong>sal ret<strong>in</strong>a (arrows). Vascularized mesenchyme has entered optic cup through<br />
ret<strong>in</strong>al p<strong>or</strong>tion of optic fissure. (x235.)<br />
optic stalk was just becom<strong>in</strong>g apparent at 11 days,<br />
but by 11.5 days it was well established <strong>in</strong> <strong>the</strong><br />
optic stalk of n<strong>or</strong>mal animals (Fig. 2, A). In mutant<br />
animals this optic stalk fissure was delayed <strong>in</strong> its<br />
f<strong>or</strong>mation and rema<strong>in</strong>ed abn<strong>or</strong>mal throughout development<br />
(Fig. 2, B). At 11.5 days only a small<br />
<strong>in</strong>trusion of neuroectodermal cells <strong>in</strong>to <strong>the</strong> stalk<br />
lumen was evident. Vascularized mesenchyme<br />
was only sparsely represented <strong>in</strong> this ventral <strong>in</strong>trusion<br />
<strong>in</strong> <strong>the</strong> mutants, whereas <strong>in</strong> n<strong>or</strong>mal animals<br />
<strong>the</strong> vessels which had <strong>or</strong>ig<strong>in</strong>ally entered <strong>the</strong> eye<br />
through <strong>the</strong> ret<strong>in</strong>al p<strong>or</strong>tion of <strong>the</strong> optic fissure<br />
eventually came to course well back <strong>in</strong>to <strong>the</strong> optic<br />
stalk fissure (Fig. 2).<br />
By 12.5 days of gestation o<strong>the</strong>r maj<strong>or</strong> differences<br />
were apparent between n<strong>or</strong>mal and mutant<br />
eyes. Ret<strong>in</strong>al ganglion cells had differentiated and<br />
had sent axons back along <strong>the</strong> optic stalk <strong>in</strong> n<strong>or</strong>mal<br />
animals, whereas <strong>in</strong> <strong>or</strong> J animals no evidence of<br />
ganglion cell differentiation was apparent. In <strong>the</strong><br />
mutant animals <strong>the</strong>re now were large numbers of<br />
degenerat<strong>in</strong>g cells <strong>in</strong> <strong>the</strong> ret<strong>in</strong>a and optic stalk,<br />
especially <strong>in</strong> <strong>the</strong> ventral region adjacent to <strong>the</strong><br />
optic fissure (Fig. 3). These necrotic foci were <strong>in</strong><br />
excess of <strong>the</strong> number seen at this time <strong>in</strong> n<strong>or</strong>mal<br />
animals. The edges of <strong>the</strong> fissure were partially<br />
overlapp<strong>in</strong>g and redundant, but <strong>the</strong>y were closely<br />
approximated and appeared to be clos<strong>in</strong>g. Some<br />
blood vessels still entered <strong>the</strong> eye through <strong>the</strong><br />
posteri<strong>or</strong> extent of <strong>the</strong> optic fissure. The mutant<br />
eye appeared slightly smaller than its n<strong>or</strong>mal control,<br />
especially <strong>in</strong> its m<strong>or</strong>e ventral p<strong>or</strong>tions.<br />
By 14.5 days of gestation, <strong>the</strong> eye and optic<br />
nerve of n<strong>or</strong>mal animals had steadily <strong>in</strong>creased <strong>in</strong><br />
volume as greater numbers of ganglion cells differentiated<br />
and sent axons back toward <strong>the</strong> bra<strong>in</strong><br />
(Fig. 4, A). In <strong>the</strong> <strong>or</strong> 1 mutant by day 15 all rema<strong>in</strong><strong>in</strong>g<br />
fissures <strong>in</strong> <strong>the</strong> ret<strong>in</strong>a and optic stalk had closed<br />
completely. A substantial ret<strong>in</strong>al neuroblastic<br />
layer was present, but it was difficult to dist<strong>in</strong>guish<br />
ganglion cells. Although <strong>the</strong>re was some <strong>in</strong>dication<br />
of nerve fiber f<strong>or</strong>mation at <strong>the</strong> <strong>in</strong>ner surface of <strong>the</strong><br />
ret<strong>in</strong>a, its development was meager, and no axons<br />
exited from <strong>the</strong> eye (Fig. 4, B). In <strong>the</strong> absence of<br />
an optic nerve, <strong>the</strong> optic stalk regressed and became<br />
a slender c<strong>or</strong>d of cells. The open<strong>in</strong>g <strong>in</strong> <strong>the</strong><br />
posteri<strong>or</strong> ret<strong>in</strong>a f<strong>or</strong> passage of <strong>the</strong> hyaloid vessels<br />
was completely closed at this stage. Blood vessels,