Purpose. We fortuitously discovered an increase in bFGF mRNA in the retina after injection of the α2-adrenergic agonist xylazine in rat. Here we show that this induction of bFGF expression was mediated by α2-adrenergic receptors, and the induced expression was retina specific. Methods. Adult male Sprague-Dawley rats were injected with the α2-adrenergic agonists xylazine, clonidine, or the antagonist yohimbine. bFGF expression in the retina was determined by Northern blot analysis. In situ hybridization was employed to localize the induced expression. Results. A single injection of xylazine (6mg/kg, i.m.) induced a 5-fold increase in bFGF mRNA in the retina by 12 hr, which declined to the baseline in 48 hr. Pre-treatment with yohimbine, an α2-adrenergic antagonist (5mg/kg, i.p., 20 min before xylazine) completely inhibited this increase. Injection of another α2-adrenergic agonist, clonidine (0.5 mg/kg, i.p.), also up-regulated bFGF mRNA in the retina with a similar temporal pattern. Pre-injection of yohimbine (15 mg/kg, i.p., 20 min before clonidine) also completely abolished the effect of clonidine. Moreover, high dosage of yohimbine (15 mg/kg, i.p.) inhibited the baseline expression of bFGF by 40%, indicating that α2-adrenergic receptors play a physiological role in regulating bFGF expression in normal retina. There was, however, no increase in bFGF mRNA in any of the eight brain regions examined (septum, striatum, thalamus, hypothalamus, hippocampus, olfactory balb, cerebellum, and cerebral cortex) after either xylazine or clonidine treatment. In situ hybridization showed that the induced bFGF expression was almost exclusively in the inner-segment region of photoreceptors. Conclusions. Our results indicate that regulation of bFGF expression in photoreceptors is unique in the central nervous system, and α2-adrenergic receptors play a role. This raises the possibility that photoreceptors could be specifically targeted, systemically, to modulate their bFGF production. Since bFGF has been shown to promote photoreceptor survival, the therapeutic potential of α2-adrenergic agonists for photoreceptor degenerative diseases should not be overlooked.
|Original language||English (US)|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Feb 15 1996|
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience