Biomedical Engineering Reference
In-Depth Information
15.4 CONCLUSIONS
Several well-establishedmethods are available for the safety testing of compounds for
adverse effects on visual function in larval zebrafish, including OMR, OKR and ERG
measurement. These methodologies, along with other larval zebrafish safety assays,
are gaining acceptance in nonclinical safety evaluation, as a means of “frontloading”
in vivo studies, because the assays are amenable to medium/high-throughput screen-
ing and chronic dosing (Valentin and Hammond, 2008). Preliminary published
observations are encouraging with predictivity of the OMR assay being reported as
70%. However, the visual function assays require further validation using a wide
range of compounds to ensure the reliability, robustness, reproducibility, and pre-
dictive value of the OMR and OKR assays. Further automation and miniaturization of
the OMR and OKR assays would improve throughput and the determination of the
amount of compound in the zebrafish larvae by mass spectrometry would help to
eliminate false negatives and transform these assays from a qualitative to quantitative
prediction of effects.
REFERENCES
B
ALM
PH and G
RONEVELD
D (1998). The melanin-concentrating hormone system in fish. Ann NYAcad Sci
839: 205-209.
B
ARROS
TP, A
LDERTON
WK, R
EYNOLDS
HM, R
OACH
AG, and B
ERGHMANS
S (2008). Zebrafish: an emerging
technology for in vivo pharmacological assessment to identify potential safety liabilities in early drug
discovery. Br J Pharmacol 154(7): 1400-1413.
B
ERGHMANS
S, B
UTLER
P, G
OLDSMITH
P, W
ALDRON
G, G
ARDNER
I, G
OLDER
Z, R
ICHARDS
FM, K
IMBER
G, R
OACH
A, A
LDERTON
W, and F
LEMING
A (2008). Zebrafish based assays for the assessment of cardiac, visual and
gut function: potential safety screens for early drug discovery. J Pharmacol Toxicol Methods 58(1):
59-68.
B
IEHLMAIER
O, N
EUHAUSS
SC, and K
OHLER
K (2003). Synaptic plasticity and functionality at the cone
terminal of the developing zebrafish retina. J Neurobiol 56(3): 222-236.
B
ILOTTA
J, S
ASZIK
S, and S
UTHERLAND
SE (2001). Rod contributions to the electroretinogram of the dark-
adapted developing zebrafish. Dev Dyn 222(4): 564-570.
B
RANCHEK
T and B
REMILLER
R (1984). The development of photoreceptors in the zebrafish, Brachydanio
rerio. I. Structure. J Comp Neurol 224(1): 107-115.
B
ROCKERHOFF
SE (2006). Measuring the optokinetic response of zebrafish larvae. Nat Protoc 1(5):
2448-2451.
B
ROCKERHOFF
SE, H
URLEY
JB, J
ANSSEN
-B
IENHOLD
U, N
EUHAUSS
SC, D
RIEVER
W, and D
OWLING
JE (1995). A
behavioral screen for isolating zebrafish mutants with visual system defects. Proc Natl Acad Sci USA
92(23): 10545-10549.
B
ROCKERHOFF
SE, H
URLEY
JB, N
IEMI
GA, and D
OWLING
JE (1997). A new form of inherited red-blindness
identified in zebrafish. J Neurosci 17(11): 4236-4242.
B
URRILL
JD andE
ASTER
SS Jr. (1995). The first retinal axons and their microenvironment in zebrafish: cryptic
pioneers and the pretract. J Neurosci 15(4): 2935-2947.
C
HIOU
G (1999). Ocular Toxicity, 2nd edition. Taylor & Francis, Philadelphia, pp. 43-86, 225-354.
E
ASTER
SS Jr. and N
ICOLA
GN (1996). The development of vision in the zebrafish (Danio rerio). Dev Biol
180(2): 646-663.
F
LEISCH
VC and N
EUHAUSS
SC (2006). Visual behavior in zebrafish. Zebrafish 3(2): 191-201.
G
OLDSMITH
P (2001). Modelling eye diseases in zebrafish. Neuroreport 12(13): A73-A77.
Search WWH ::
Custom Search