The introduction of beta-adrenergic blocking agents for the treatment of glaucoma was a major advance in the continued search for medications that effectively control the intraocular pressure with minimal side effect. Beta-adrenergic blocking agents block the aqueous pump of the ciliary epithelium resulting in decreased aqueous formation and drop in intraocular pressure. The fact that beta-adrenergic blocking agents had an affinity to intraocular tissues containing melanin granules has been reported. The purpose of this study is to know that mechanism of decrease of intraocular pressure and an affinity to melanin granules of the beta-adrenergic blocking agents. Two drops of 1% befunolol were instilled in the albino and pigmented rabbits, and the eyes were enucleated on 1, 2, 6 and 24 hours after instillation. These eyes were studied with electron microscopic examination. The results were as follows: 1. In the non-pigment epithelium of the ciliary body, mitochondria became swollen. 2. These changes appeared earlier and were more remarkable in albino rabbits than in pigmented ones. 3. In pigmented rabbits, these changes appeared slowly, but continued for longer duration and it seems to be due to affinity of beta-adrenergic blocking agents to the melanin pigment. 4. Swelling of mitochondria at the non-pigmented epithelium of the ciliary body after instillation of beta-adrenergic blocking agents seems to be the pharmacological mechanism of the drugs against aqueous formation in the ciliary body.
Adrenergic beta-Antagonists ; Ciliary Body ; Epithelium* ; Glaucoma ; Intraocular Pressure ; Melanins ; Mitochondria ; Rabbits

Xanthohumol (XH), the principal prenylflavonoid of the hop plant (Humulus lupulus L.), dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis in B16 melanoma cells, with little cytotoxicity at the effective concentrations. Decreased melanin content was accompanied by reduced tyrosinase enzyme activity, protein and mRNA expression. The levels of tyrosinase-related protein 1 and 2 mRNAs were decreased by XH. XH also inhibited alpha-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. XH downregulated the protein and mRNA expression of microphthalmia-associated transcription factor (MITF), a master transcriptional regulator of key melanogenic enzymes. These results suggest that XH might act as a hypo-pigmenting agent through the downregulation of MITF in the cAMP-dependent melanogenic pathway.
1-Methyl-3-isobutylxanthine/pharmacology ; Animals ; Cell Line ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Down-Regulation ; Drug Antagonism ; Forskolin/pharmacology ; *Humulus ; Intramolecular Oxidoreductases/antagonists & inhibitors/biosynthesis ; Melanins/antagonists & inhibitors/*biosynthesis ; Melanocytes/*drug effects/*metabolism ; Melanoma, Experimental ; Membrane Glycoproteins/antagonists & inhibitors/biosynthesis ; Mice ; Microphthalmia-Associated Transcription Factor/antagonists & inhibitors ; Monophenol Monooxygenase/antagonists & inhibitors/biosynthesis/genetics ; Oxidoreductases/antagonists & inhibitors/biosynthesis ; Propiophenones/*pharmacology ; Signal Transduction/drug effects ; alpha-MSH/metabolism