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U. Napankangas, U. Lonngren, M. Lafuente, N. Lindqvist, S. Mayor, I. Cànovas, M. Vidal–Sanz, F. Hallbook; The Expression of Growth Factors and Their Receptors After Transient Retinal Ischemia – Modulation by Alpha–2–Receptor Stimulation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4837.
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We studied the expression of Bdnf, Nt3, Fgf2, Fgf1, Cntf, and their receptors (TrkB, TrkC, Fgfr1, Cntfr–alpha) after an ischemic insult to evaluate their participation in an injury–induced response. In order to examine possible modulating effects of alpha–2–adrenergic receptor stimulation on the mRNA expression after ischemia, animals were treated with the receptor agonist brimonidine.
90 minutes of retinal ischemia was induced by selective ligature of the ophthalmic vessels of one eye of adult Sprague Dawley rats. Prior to surgery, animals were treated topically with 2 x 5 µl 0.5 % brimonidine or vehicle (0.9 % NaCl). Left retinas were collected 1, 3, 7, or 14 days after injury and analyzed using qRT–PCR. The results were normalized to beta–actin and related to normal retinal levels. Thy1 mRNA level was analyzed as a measure of ganglion cell injury.
The injury evoked a transient and significant increase in mRNA levels of Cntf, Fgf2, Nt3 and Fgfr1, whereas a decrease was detected in Thy1, TrkB and TrkC mRNAs. The mRNA levels of Bdnf, Fgf1 and Cntfr–alpha were not altered. Brimonidine–treated retinas showed significantly higher Bdnf, Cntf, Nt3, Fgf2, Fgf1 and Fgfr4 mRNA levels at several time points after ischemia both compared to normal and ischemic vehicle–treated retinas. TrkB and TrkC levels did not decrease after ischemia in the brimonidine treated retinas. Fgf1, Fgfr1 and Cntfr–alpha levels were not altered.
Ischemia induces alterations in the expression of growth factors and their receptors in retina. The decrease of Thy–1, TrkB and TrkC mRNA is likely to reflect the injury of ganglion cells. The increase of Cntf and Fgf2 as well as Nt3 and Fgfr1 is part of an injury–induced response that may contribute to diminish the effects of the injury. Brimonidine has been shown to reduce retinal cell injury after ischemia and the increased expression of neurotrophic factors and receptors after treatment are most likely part of the neuroprotective mechanisms of brimonidine.
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