Abstract
We have investigated the possibility that direct cellular effects may mediate the action of EPI to lower the IOP. To do this, cultured HTM and SCE cells were grown as monolayers over a millipore-filter support structure. The monolayers were exposed to various adrenergic agonists and antagonists while flow of the perfusate (DME + 5% FBS) was measured using a specially-designed computer-linked apparatus. Exposure of the cells to 10(-5) M EPI for around 2 hours led to a rapid twofold increase in HC which gradually declines over the next 12 hours. Continuous exposure of either cell type (ie, HTM or SCE cells) to EPI or ISO resulted in a four- to eightfold increase with a maximal effect measured around 10 hours and a half maximal effect at 2.5 hours. Administration of c-AMP alone gave similar responses. In agreement with clinical studies, timolol blocks EPI's effect completely while betaxolol acted as a partial antagonist. These findings suggest that the cellular changes and the increase in HC are mediated by a beta-2 receptor. There are many similarities between the responses observed using our in vitro system and the IOP-lowering response observed in vivo after the topical application of EPI (eg, concentration, time course, duration, and magnitude). The clinical implications of these preliminary results are discussed and it is proposed that the described in vitro system may be useful to select new adrenergic drugs for glaucoma therapy.
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- Alexander D. W., Berson F. G., Epstein D. L. A clinical trial of timolol and epinephrine in the treatment of primary open-angle glaucoma. Ophthalmology. 1988 Feb;95(2):247–251. doi: 10.1016/s0161-6420(88)33205-7. [DOI] [PubMed] [Google Scholar]
- Allen R. C., Epstein D. L. Additive effect of betaxolol and epinephrine in primary open angle glaucoma. Arch Ophthalmol. 1986 Aug;104(8):1178–1184. doi: 10.1001/archopht.1986.01050200084056. [DOI] [PubMed] [Google Scholar]
- Alvarado J. A., Wood I., Polansky J. R. Human trabecular cells. II. Growth pattern and ultrastructural characteristics. Invest Ophthalmol Vis Sci. 1982 Oct;23(4):464–478. [PubMed] [Google Scholar]
- Alvarado J., Murphy C., Juster R. Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normals. Ophthalmology. 1984 Jun;91(6):564–579. doi: 10.1016/s0161-6420(84)34248-8. [DOI] [PubMed] [Google Scholar]
- Alvarado J., Murphy C., Polansky J., Juster R. Age-related changes in trabecular meshwork cellularity. Invest Ophthalmol Vis Sci. 1981 Nov;21(5):714–727. [PubMed] [Google Scholar]
- BALLINTINE E. J., GARNER L. L. Improvement of the co-efficient of outflow in glaucomatous eyes. Prolonged local treatment with epinephrine. Arch Ophthalmol. 1961 Sep;66:314–317. doi: 10.1001/archopht.1961.00960010316004. [DOI] [PubMed] [Google Scholar]
- Kronfeld P. C. Early effects of single and repeated doses of L-epinephrine in man. Am J Ophthalmol. 1971 Dec;72(6):1058–1072. doi: 10.1016/0002-9394(71)91211-6. [DOI] [PubMed] [Google Scholar]
- Neufeld A. H., Jumblatt M. M., Matkin E. D., Raymond G. M. Maintenance of corneal endothelial cell shape by prostaglandin E2: effects of EGF and indomethacin. Invest Ophthalmol Vis Sci. 1986 Oct;27(10):1437–1442. [PubMed] [Google Scholar]
- Neufeld A. H., Sears M. L. Adenosine 3',5'-monophosphate analogue increases the outflow facility of the primate eye. Invest Ophthalmol. 1975 Sep;14(9):688–689. [PubMed] [Google Scholar]
- Perkins T. W., Alvarado J. A., Polansky J. R., Stilwell L., Maglio M., Juster R. Trabecular meshwork cells grown on filters. Conductivity and cytochalasin effects. Invest Ophthalmol Vis Sci. 1988 Dec;29(12):1836–1846. [PubMed] [Google Scholar]
- Polansky J. R., Alvarado J. A. Isolation and evaluation of target cells in glaucoma research: hormone receptors and drug responses. Curr Eye Res. 1985 Mar;4(3):267–279. doi: 10.3109/02713688509000858. [DOI] [PubMed] [Google Scholar]
- Polansky J., Friedman Z., Fauss D., Kurtz R., Alvarado J. Effects of betaxolol/timolol on epinephrine stimulated cyclic-AMP levels in human trabecular meshwork cells. Int Ophthalmol. 1989 Jan;13(1-2):95–97. doi: 10.1007/BF02028646. [DOI] [PubMed] [Google Scholar]
- Schenker H. I., Yablonski M. E., Podos S. M., Linder L. Fluorophotometric study of epinephrine and timolol in human subjects. Arch Ophthalmol. 1981 Jul;99(7):1212–1216. doi: 10.1001/archopht.1981.03930020086007. [DOI] [PubMed] [Google Scholar]
- Shirato S., Murphy C. G., Bloom E., Franse-Carman L., Maglio M. T., Polansky J. R., Alvarado J. A. Kinetics of phagocytosis in trabecular meshwork cells. Flow cytometry and morphometry. Invest Ophthalmol Vis Sci. 1989 Dec;30(12):2499–2511. [PubMed] [Google Scholar]
- Thomas J. V., Epstein D. L. Timolol and epinephrine in primary open angle glaucoma. Transient additive effect. Arch Ophthalmol. 1981 Jan;99(1):91–95. doi: 10.1001/archopht.1981.03930010093010. [DOI] [PubMed] [Google Scholar]
- Townsend D. J., Brubaker R. F. Immediate effect of epinephrine on aqueous formation in the normal human eye as measured by fluorophotometry. Invest Ophthalmol Vis Sci. 1980 Mar;19(3):256–266. [PubMed] [Google Scholar]
- Wei C. P., Anderson J. A., Leopold I. Ocular absorption and metabolism of topically applied epinephrine and a dipivalyl ester of epinephrine. Invest Ophthalmol Vis Sci. 1978 Apr;17(4):315–321. [PubMed] [Google Scholar]
- Yun A. J., Murphy C. G., Polansky J. R., Newsome D. A., Alvarado J. A. Proteins secreted by human trabecular cells. Glucocorticoid and other effects. Invest Ophthalmol Vis Sci. 1989 Sep;30(9):2012–2022. [PubMed] [Google Scholar]