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X. Song, S. A. Vishnivetskiy, J. Chen, V. V. Gurevich; Evaluation the Effects of Transgenic Manipulation of Arrestin1 Expression Level on Retinal Rod Function. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5424.
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Arrestin1 binds phosphorylated rhodopsin and shuts off light response. Transgenic mice lacking arrestin1 show prolonged recovery, indicating the critical role of arrestin1 in photoresponse recovery. We used transgenic mice to investigate how arrestin1 expression levels affect the morphology and functional performance of rod photoreceptors.
We generated mice expressing arrestin1 at levels ranging from 3% to 240% of arrestin1 expression in wild type (WT) animals. Morphology was evaluated using the length of the outer segments (OS) and thickness of outer nuclear layer. The functional performance of the rods was evaluated using single- and double-flash ERG.
WT mice express arrestin1 at 0.8:1 ratio to rhodopsin. We show that the fraction of arrestin1 in the OS of dark-adapted rods is proportional to its overall expression level. Rapid recovery requires arrestin1 expression level at least 7% of WT. Arrestin1 protects rods expressing as little as ~3% of WT level (as compared to Arr1 knockout mice), but these animals demonstrate 3-8 times slower photoresponse recovery than WT mice. The OS in WT mice are longer and healthier than in animals expressing arrestin1 at higher or lower levels. However, at 6 weeks transgenic lines expressing arrestin1 at 140% and 190% of WT level demonstrate more robust photoresponses, faster recovery, and higher light sensitivity.
Arrestin1 concentration in the OS in the dark determines the recovery kinetics and light sensitivity of rods. Higher than WT arrestin1 concentration in the OS improves rod performance and facilitates recovery, but it is detrimental for rod health. Thus, arrestin1 expression level in WT animals is a compromise between optimal performance and long-term photoreceptor survival.
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