Abstract
• Background: Minoxidil is an inhibitor of lysyl hydroxylase, an enzyme involved in collagen production, and decreases collagen production in vitro. We investigated the in vitro effects of minoxidil on behavior such as proliferation and migration of rabbit subconjunctival fibroblasts (SCFs). The ultrastructural effect of the drug on SCFs was also examined. • Methods: Proliferation of SCFs and closure of the defect produced in monolayer cultures in the presence or absence of minoxidil was studied. The ultrastructure of SCFs treated with minoxidil was also examined. • Results: Minoxidil inhibited SCF proliferation and the closure of the defect produced in monolayer cell sheets. Ultrastructural observations revealed extensive areas of irregularly dilated endoplasmic reticulum in cells treated with minoxidil, indicating the accumulation of protein, probably underhydroxylated collagen precursors, in the cisternae of endoplasmic reticulum. • Conclusions: The results indicated that minoxidil attenuated cellular activities of SCFs such as proliferation and migration in vitro. The exact mechanism of the inhibitory effects of minoxidil on these cellular activities is unknown. The findings suggest that the drug might help to prevent bleb scarring after glaucoma filtering surgery.
Similar content being viewed by others
References
Costa VP, Speath GL, Eiferman RA, Orengo-Nania S (1993) Wound healing modulation in glaucoma filtration surgery. Ophthalmic Surg 24:152–170
Desjardins DC, Parrish RK II, Folberg R, Nevarez J, Heuer DK, Gressel MG (1986) Wound healing after filtering surgery in owl monkeys. Arch Ophthalmol 104:1835–1839
Handa JT, Murad S, Jaffe GJ (1993) Minoxidil inhibits ocular cell proliferation and lysyl hydroxylase activity. Invest Ophthalmol Vis Sci 34:567–575
Heuer DK, Parrish PK II, Gressel MG, Hodapp E, Palmberg PF, Anderson DR (1984) 5-Fluorouracil and glaucoma filtering surgery. III. Intermediate follow-up of a pilot study. Ophthalmology 91:384–394
Jampel HD (1992) Effect of brief exposure to mitomycin C on viability and proliferation of human Tenon's capsule fibroblasts. Ophthalmology 99:1471–1476
Jampel HD, McGuigan LJB, Dunkelberger GR, L'Hernault NL, Guigley HA (1988) Cellular proliferation after experimental glaucoma filtration surgery. Arch Ophthalmol 106:89–94
Khaw PT, Sherwood MB, Mackey SLD, Rossi MJ, Schultz G (1992) Five-minute treatments with fluorouracil, floxuridine, and mitomycin have long-term effects on human Tenon's capsule fibroblasts. Arch Ophthalmol 110:1150–1154
Kitazawa Y, Kawase K, Matsushita H, Minobe M (1991) Trabeculectomy with mitomycin. A comparative study with fluorouracil. Arch Ophthalmol 109:1693–1698
Kivirikko KI, Myllyla R (1985) Post-translational processing of procollagens. Ann NY Acad Sci 460:187–201
Kucharz EJ (1992) The collagens: biochemistry and pathophysiology. Springer, Berlin Heidelberg New York, pp 31–53
Kurisu K, Ohsaki Y, Inai T, Kukita T (1992) Heterogenous distribution of the precursors of type I and type III collagen and fibronectin in the rough endoplasmic reticulum of palatal mesenchymal cells of the mouse embryo cultured in ascorbate-depleted medium. Cell Tissue Res 267:429–435
Liotta LA, Vembu D, Kleinmann HK, Martin GR, Boone C (1978) Collagen required for proliferation of cultured connective tissue cells but not their transformed counterparts. Nature 272:622–624
McGuigan LJB, Mason RP, Sanchez R, Quigley HA (1987) d-Penicillamine and beta-aminopropionitrile effects on experimental filtering surgery. Invest Ophthalmol Vis Sci 28:1625–1629
Miller HM, Grierson I, Unger WI, Hitchings RA (1989) Wound healing in an animal model of glaucoma fistulizing surgery in the rabbit. Ophthalmic Surg 20:350–357
Murad S, Pinnel SR (1987) Suppression of fibroblast proliferation and lysyl hydroxylase activity by minoxidil. J Biol Chem 262:11973–11978
Nomura H, Ishiguro T, Morimoto S (1969) Studies on l-ascorbic acid derivatives. I. Bis-(l-ascorbic acid-3,3′)-phosphate and l-ascorbic-acid 2-phosphate. Chem Pharm Bull (Tokyo) 17:387–393
Nugent MA, Newman MJ (1989) Inhibition of normal rat kidney cell growth by transforming growth factor-b is mediated by collagen. J Biol Chem 264:18060–18067
Pasquale LR, Thibault D, Dorman-Pease ML, Quigley HA, Jampel HD (1992) Effect of topical mitomycin C on glaucoma filtration surgery in monkeys. Ophthalmology 99:14–18
Saika S (1993) Ultrastructural effect of l-ascorbic acid 2-phosphate on cultured keratocytes. Cornea 11:439–445
Saika S, Kanagawa R, Uenoyama S, Hiroi K, Hiraoka J (1991) l-Ascorbic acid 2-phosphate, a phosphate derivative of l-ascorbic acid, enhances the growth of cultured rabbit keratocytes. Graefes Arch Clin Exp Ophthalmol 229:79–83
Saika S, Uenoyama K, Ooshima A, Hiroi K (1992) l-Ascorbic acid 2-phosphate enhances the production of type I and type III collagen peptides in cultured rabbit keratocytes. Ophthalmic Res 24:68–72
Saika S, Yamanaka O, Hashizume N, Kobata S, Okada Y, Uenoyama K, Ooshima A (1993) Proline analog inhibits adhesion, migration, and proliferation of cultured rabbit keratocytes. Ophthalmic Res 25:363–370
Saika S, Hashizume N, Kobata S, Yamanaka O, Okada Y, Uenoyama K, Ooshima A (1994) Prolyl hydroxylase inhibitor and lysyl hydroxylase inhibitor inhibit spreading of corneal epithelium. Graefes Arch Clin Exp Ophthalmol 232:499–502
Sasaki T, Majjama K, Uitto J (1987) Reduction of collagen production in keloid fibroblast cultures by ethyl-3,4-dihydroxy-benzoate. J Biol Chem 262:9397–9403
Stenn KS, Madri JA, Roll FJ (1979) Migrating epidermis produces AB2 collagen and requires continuous collagen synthesis for movement. Nature 277:229–232
Tan EML, Ryhanen L, Uitoo J (1983) Proline analogs inhibit skin fibroblast growth and collagen production in culture. J Invest Dermatol 80:261–267
Weinrab RN (1987) Adjusting the dose of 5-fluorouracil after filtering surgery to minimize side effects. Ophthalmology 94:564–570
Yamamoto T, Varani J, Soong HK, Lichter PR (1990) Effects of 5-fluorouracil and mitomycin C on cultured rabbit subconjunctival fibroblasts. Ophthalmology 97:1204–1210
Yeowell HN, Ha V, Walker LC, Murad S, Pinnel SR (1992) Characterization of a partial cDNA for lysyl hydroxylase from human skin fibroblasts: lysyl hydroxylase mRNAs are regulated differently by minoxidil derivatives and hydralazine. J Invest Dermatol 99:864–869
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Saika, S., Ooshima, A., Hashizume, N. et al. Effect of a lysyl hydroxylase inhibitor, minoxidil, on ultrastructure and behavior of cultured rabbit subconjunctival fibroblasts. Graefe's Arch Clin Exp Ophthalmol 233, 347–353 (1995). https://doi.org/10.1007/BF00200483
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00200483