Molecular imaging of retinal gliosis in transgenic mice induced by kainic acid neurotoxicity.
OBJECTIVE
Gliosis is a universal response of the central nervous system to diverse insults. Here the authors aimed to develop a noninvasive fluorescence system to monitor and quantify retinal gliosis in real time.


METHODS
Transgenic mice expressing green fluorescent protein (GFP) under the control of the glial fibrillary acidic protein promoter were treated with excitatory neurotoxicant kainic acid (KA) through a single intraperitoneal injection to induce gliosis in the brain and the retina. The expression of the GFAP-GFP transgene as a surrogate reporter for gliosis was noninvasively and longitudinally imaged with a confocal scanning laser ophthalmoscope for 2 weeks to monitor the progression of gliosis.


RESULTS
The authors demonstrated that KA-induced gliosis (an elevation in GFP fluorescence intensity [FI]) could be noninvasively detected starting on day 3 and that it peaked on day 7, as quantified for the optic disc astrocytes. A significant increase in the FI in retinal glial cells was also visible on the processed images. Immunohistochemistry in defined regions of the brain (hippocampal CA1, CA3, dentate gyrus) known to be affected by KA neurotoxicity showed that severe gliosis in these regions occurred at day 7, when retinal gliosis peaked.


CONCLUSIONS
The current real-time fluorescent imaging method described here is a powerful preclinical tool to directly monitor retinal gliosis caused by various retinopathies. In addition, this molecular imaging method should be useful in assessing retinal neurotoxicity and in therapeutic development in a preclinical setting.
Ho
Gideon
G
Institute of Bioengineering and Nanotechnology, Singapore.
Kumar
Saravana
S
Min
Xiao Shan
XS
Kng
Yin Ling
YL
Loh
Ming Yang
MY
Gao
Shujun
S
Zhuo
Lang
L
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000175:diagnosis; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005453:Fluorescence; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000175:diagnosis*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D020258:Neurotoxicity Syndromes / Q000175:diagnosis / Q000209:etiology; D019721:Ophthalmoscopes; D009900:Optic Nerve / Q000601:surgery; D012164:Retinal Diseases / Q000139:chemically induced / Q000175:diagnosis*
D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D007608:Kainic Acid