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H. Takase, C. C. Chan, M. Santos-Muffley, J. Tuo, B. P. Vistica, M. Mochizuki, I. Gery; Microarray Analysis of Gene Expression in Light Exposed Mouse Retina: A Comparison Between Light-Damage Susceptible and Resistant Strains. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4417.
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© ARVO (1962-2015); The Authors (2016-present)
Excessive light causes retinal photoreceptor degeneration, and there is a wide variability among mouse strains in their susceptibility to light damage (LD) due to level of pigmentation as well as genetic background. This study was aimed at comparing changes of retinal genes between LD susceptible and resistant mouse strains following exposure to light.
LD susceptible mice included albino BALB/c and a line of mice homozygous for Leu (Leu/Leu) at position 450 of RPE65, backcrossed into C57Bl/6. A line of C57Bl/6 mice expressing Met/Met at that position was the LD resistant line. All mice were exposed to 5000 lux white fluorescent light continuously for 7 (BALB/c) or 14 (C57Bl/6) days. Control mice of the same lines were kept in cyclic colony room light. Immediately after exposure to light, the mice were euthanized, one eye of each mouse was used for histological analysis, whereas the retina from the fellow eye was processed for total RNA extraction followed by Affymetrix DNA microarray analysis, to compare gene expression in light damaged mice and their corresponding controls.
Severe photoreceptor (inner and outer segments of photoreceptor layer, and outer nuclear layer) loss was observed in light exposed BALB/c and Leu/Leu mice, while only slightly shortened inner and outer segments of photoreceptors were noted in the LD resistant Met/Met strain. Microarray analysis revealed that the number of genes up- or down-regulated over 2 fold in light exposed retinas, compared to the corresponding controls, was 1771 in BALB/c, 740 in the Leu/Leu mice, and 127 in Met/Met mice. BALB/c and Leu/Leu mice had 191 up-regulated genes (e.g., nupr1, Lyzs, Ifi202b, and Oasl2) and 344 down-regulated genes (e.g., Grk1, Gucy2e, Slc6a6, and B3gat1) in common. Only 22 up-regulated genes (e.g., Cebpd, Egr1, SOCS3, and Edn2) and 12 down-regulated genes (e.g., Dscaml1, Wisp1, Gas7, and Fscn2) were common to all three tested lines.
The number of retinal genes that changed after light exposure was higher in the two LD susceptible strains as compared with the LD resistant mice. Expression of a substantial number of the same genes was affected by light exposure in the two susceptible strains.
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