Levobetaxolol-induced Up-regulation of retinal bFGF and CNTF mRNAs and preservation of retinal function against a photic-induced retinopathy.
Betaxolol (racemic), a beta-adrenoceptor antagonist that is used to lower intraocular pressure in the treatment of glaucoma, has been shown to protect inner retina cells from various insults. To determine if such protection could be afforded to retinal photoreceptors and retinal pigment epithelial cells (RPE), levobetaxolol (S-betaxolol) was evaluated in a photic-induced retinopathy model. Rats were dosed (IP) with vehicle or levobetaxolol (10 and 20 mg kg(-1)) 48, 24 and 0 hr prior to exposure for 6 hr to fluorescent blue light. The electroretinogram (ERG) and retinal morphology were assessed after a 3 week recovery period. Evaluation of the ERG demonstrated significant protection of retinal function in levobetaxolol (20 mg kg(-1))-dosed rats compared to vehicle-dosed rats. Similarly, the RPE and outer nuclear layer were significantly thicker in levobetaxolol (20 mg kg(-1))-dosed rats compared to vehicle-dosed rats. To elucidate potential mechanism(s) of the neuroprotective activity of levobetaxolol, bFGF and CNTF mRNA levels in normal rat retinas were evaluated 12 hr after a single i.p. injection. Northern blot analysis of levobetaxolol treated retinas demonstrated a 10-fold up-regulation of bFGF and a two-fold up-regulation of CNTF mRNA levels, trophic factors that have been shown to inhibit retinal degeneration in a number of species. These studies suggest that levobetaxolol can be used as a novel neuroprotective agent to ameliorate retinopathy.
Agarwal
Neeraj
N
Department of Pathology and Anatomy, Division of Cell Biology and Genetics, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA.
Martin
Elizabeth
E
Krishnamoorthy
Raghu R
RR
Landers
Robert
R
Wen
Rong
R
Krueger
Scott
S
Kapin
Michael A
MA
Collier
Robert J
RJ
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D015784:Betaxolol / Q000627:therapeutic use*; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics; D008027:Light; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D011832:Radiation Injuries / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism; D012162:Retinal Degeneration / Q000517:prevention & control*; D015854:Up-Regulation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D020934:Ciliary Neurotrophic Factor; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D015784:Betaxolol