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The Histopathology of Corneal Neovascularization: Inhibitor Effects

The Histopathology of Corneal Neovascularization: Inhibitor Effects Abstract • With the use of a previously described model of corneal neovascularization induced by thermal cautery, we examined the effects of inhibitors on both the incidence of corneal neovascularization and the degree of inflammatory cell response. Three known inhibitors of corneal neovascularization, 1% prednisolone acetate, indomethacin, and 0.3% flurbiprofen, were studied and the results were compared with those in saline-treated controls. As expected, corneal neovascularization, preceded by conjunctival and corneal polymorphonuclear leukocyte (PMNL) infiltration, occurred in all control animals. Corneal neovascularization did not occur in any of the inhibitor-treated eyes. Histopathologically, both conjunctival and corneal PMNL counts in the treated eyes were markedly reduced compared with controls. These findings are consistent with the hypothesis that inflammatory cells, particularly PMNLs, are closely associated with the initiation of corneal neovascularization. References 1. Cogan DG: Vascularization of the cornea: Its experimental induction by small lesions and a new theory of its pathogenesis . Arch Ophthalmol 1949;41:406-416.Crossref 2. Ashton N, Cook C, Langham M: Effect of cortisone on vascularization and opacification of the cornea induced by alloxan . Br J Ophthalmol 1951;35:718-724.Crossref 3. Campbell FW, Michaelson IC: Blood-vessel formation in the cornea . Br J Ophthalmol 1949; 33:248-255.Crossref 4. Zauberman H, Michaelson I, Bergmann F, et al: Stimulation of neovascularization of the cornea by biogenic amines . Exp Eye Res 1969; 8:77-83.Crossref 5. Berman M, Winthrop S, Auspring D, et al: Plasminogen activator (urokinase) causes vascularization of the cornea . Invest Ophthalmol Vis Sci 1982;22:191-199. 6. Berman M, Leary R, Gage J: Evidence for a role of the plasminogen activator-plasmin system in cornea ulceration . Invest Ophthalmol Vis Sci 1980;19:1204-1221. 7. Lagoutte F: Cornée et néovascularisation. Essai physiopathologique . J Fr Ophthalmol 1981;4:531-539. 8. BenEzra D: Neovasculogenic ability of prostaglandins, growth factors, and synthetic chemoattractants . Am J Ophthalmol 1978;86:455-461. 9. Eliason JA: Leukocytes and experimental corneal neovascularization . Invest Ophthalmol Vis Sci 1979;18:172-178. 10. Fromer CH, Klintworth GK: An evaluation of the role of leukocytes in the pathogenesis of experimentally induced corneal vascularization: I. Comparison of experimental models of corneal vascularization . Am J Pathol 1975;79:537-544. 11. Fromer CH, Klintworth GK: An evaluation of the role of leukocytes in the pathogenesis of experimentally induced corneal vascularization: II. Studies on the effect of leukocytic elimination on corneal vascularization . Am J Pathol 1975; 81:531-544. 12. Fromer CH, Klintworth GK: An evaluation of the role of leukocytes in the pathogenesis of experimentally induced corneal vascularization: III. Studies related to the vasoproliferative capability of polymorphonuclear leukocytes . Am J Pathol 1976;82:157-170. 13. Epstein RJ, Hughes WF: Lymphocyteinduced corneal neovascularization: A morphologic assessment . Invest Ophthalmol Vis Sci 1981; 22:191-199. 14. Schanzlin DJ, Cyr RJ, Friedlander MD: Histopathology of corneal neovascularization . Arch Ophthalmol 1983;101:472-474.Crossref 15. Phillips K, Arffa R, Cintron C, et al: Effects of prednisolone and medroxyprogesterone on corneal wound healing, ulceration, and neovascularization . Arch Ophthalmol 1983; 101:640-643.Crossref 16. Deutsch TA, Hughes WF: Suppressive effects of indomethacin on thermally induced neovascularization of rabbit corneas . Am J Ophthalmol 1979;87:536-540. 17. Cooper CA, Bergamini MVW, Leopold IH: Use of flurbiprofen to inhibit corneal neovascularization . Arch Ophthalmol 1980;98:1102-1105.Crossref 18. Sholley MM, Gimbrone MA Jr, Cotran RS: The effects of leukocyte depletion on corneal neovascularization . Lab Invest 1978;38:32-40.Crossref 19. Kulkarni PS, Bhattacherjee P, Eakins KE, et al: Anti-inflammatory effects of betamethasone phosphate, dexamethasone phosphate and indomethacin on rabbit ocular inflammation induced by bovine serum albumin . Curr Eye Res 1981;1:43-47.Crossref 20. Eakins KE: Prostaglandin and non-prostaglandin mediated breakdown of the blood-aqueous barrier . Exp Eye Res 1977;25( (suppl) ):483-489.Crossref 21. Kulkarni PS, Srinivasan BD: The effect of intravitreal and topical prostaglandins on intraocular inflammation . Invest Ophthalmol Vis Sci 1982;23:383-392. 22. Higgs GA, McCall E, Youlten LJF: A chemotactic role for prostaglandins released from polymorphonuclear leucocytes during phagocytosis . Br J Pharmacol 1975;53:539-546.Crossref 23. Adams SS, Burrows CA, Skeldon N, et al: Inhibition of prostaglandin synthesis and leucocyte migration by flurbiprofen . Curr Med Res Opin 1977;5:11-16.Crossref 24. Bray MA, Franco M: Prostaglandins and inflammatory cell movement in vitro . Int Arch Allergy Appl Immunol 1978;56:500-506.Crossref 25. Shibuya E, Masuda K, Izawa Y: Effects of prostaglandins on leukocyte migration . Prostaglandins 1976;12:165-174.Crossref 26. Walker JR, Smith MJH, Ford-Hutchinson AW: Prostaglandins and leucotaxis . J Pharm Pharmacol 1976;28:745-747.Crossref 27. Chang J, Lewis GP, Piper PJ: The effect of anti-inflammatory drugs on the prostaglandin system in human subcutaneous adipose tissue . Br J Ophthalmol 1977;61:446-447.Crossref 28. Chandrabose KA, Lapetina EG, Schmitges CJ, et al: Action of corticosteroids in regulation of prostaglandin synthesis . Proc Natl Acad Sci USA 1978;75:214-217.Crossref 29. Kulkarni PS, Srinivasan BD: Steroidal and nonsteroidal anti-inflammatory drugs in ocular inflammation . Ocular Inflammation Ther 1983; 1:11-18. 30. Duffin RM, Weissman BA, Glasser DB, et al: Flurbiprofen in the treatment of corneal neovascularization induced by contact lenses . Am J Ophthalmol 1982;93:607-614. 31. Jaffe EB, Podos SM, Becker B: Indomethacin blocks arachidonic acid associated elevations of aqueous humor prostaglandin E . Invest Ophthalmol Vis Sci 1973;12:621-622. 32. Podos SM: Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease . Trans Am Ophthalmol Soc 1977;74:637-660. 33. Hanna C, Keatts HC: Indomethacin in ocular inflammation in the rabbit . Arch Ophthalmol 1967;99:681-682. 34. Miller D, Gruenberg P, Miller R, et al: Topical flurbiprofen or prednisolone: Effect on corneal wound healing in rabbits . Arch Ophthalmol 1981;99:681-682.Crossref 35. Srinivasan BD, Kulkarni PS: Polymorphonuclear leukocyte response: Inhibition following corneal epithelial denudation by steroidal and nonsteroidal anti-inflammatory agents . Arch Ophthalmol 1981;99:1085-1089.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

The Histopathology of Corneal Neovascularization: Inhibitor Effects

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Publisher
American Medical Association
Copyright
Copyright © 1985 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1985.01050020136037
Publisher site
See Article on Publisher Site

Abstract

Abstract • With the use of a previously described model of corneal neovascularization induced by thermal cautery, we examined the effects of inhibitors on both the incidence of corneal neovascularization and the degree of inflammatory cell response. Three known inhibitors of corneal neovascularization, 1% prednisolone acetate, indomethacin, and 0.3% flurbiprofen, were studied and the results were compared with those in saline-treated controls. As expected, corneal neovascularization, preceded by conjunctival and corneal polymorphonuclear leukocyte (PMNL) infiltration, occurred in all control animals. Corneal neovascularization did not occur in any of the inhibitor-treated eyes. Histopathologically, both conjunctival and corneal PMNL counts in the treated eyes were markedly reduced compared with controls. These findings are consistent with the hypothesis that inflammatory cells, particularly PMNLs, are closely associated with the initiation of corneal neovascularization. References 1. Cogan DG: Vascularization of the cornea: Its experimental induction by small lesions and a new theory of its pathogenesis . Arch Ophthalmol 1949;41:406-416.Crossref 2. Ashton N, Cook C, Langham M: Effect of cortisone on vascularization and opacification of the cornea induced by alloxan . Br J Ophthalmol 1951;35:718-724.Crossref 3. Campbell FW, Michaelson IC: Blood-vessel formation in the cornea . Br J Ophthalmol 1949; 33:248-255.Crossref 4. Zauberman H, Michaelson I, Bergmann F, et al: Stimulation of neovascularization of the cornea by biogenic amines . Exp Eye Res 1969; 8:77-83.Crossref 5. Berman M, Winthrop S, Auspring D, et al: Plasminogen activator (urokinase) causes vascularization of the cornea . Invest Ophthalmol Vis Sci 1982;22:191-199. 6. Berman M, Leary R, Gage J: Evidence for a role of the plasminogen activator-plasmin system in cornea ulceration . Invest Ophthalmol Vis Sci 1980;19:1204-1221. 7. Lagoutte F: Cornée et néovascularisation. Essai physiopathologique . J Fr Ophthalmol 1981;4:531-539. 8. BenEzra D: Neovasculogenic ability of prostaglandins, growth factors, and synthetic chemoattractants . Am J Ophthalmol 1978;86:455-461. 9. Eliason JA: Leukocytes and experimental corneal neovascularization . Invest Ophthalmol Vis Sci 1979;18:172-178. 10. Fromer CH, Klintworth GK: An evaluation of the role of leukocytes in the pathogenesis of experimentally induced corneal vascularization: I. Comparison of experimental models of corneal vascularization . Am J Pathol 1975;79:537-544. 11. Fromer CH, Klintworth GK: An evaluation of the role of leukocytes in the pathogenesis of experimentally induced corneal vascularization: II. Studies on the effect of leukocytic elimination on corneal vascularization . Am J Pathol 1975; 81:531-544. 12. Fromer CH, Klintworth GK: An evaluation of the role of leukocytes in the pathogenesis of experimentally induced corneal vascularization: III. Studies related to the vasoproliferative capability of polymorphonuclear leukocytes . Am J Pathol 1976;82:157-170. 13. Epstein RJ, Hughes WF: Lymphocyteinduced corneal neovascularization: A morphologic assessment . Invest Ophthalmol Vis Sci 1981; 22:191-199. 14. Schanzlin DJ, Cyr RJ, Friedlander MD: Histopathology of corneal neovascularization . Arch Ophthalmol 1983;101:472-474.Crossref 15. Phillips K, Arffa R, Cintron C, et al: Effects of prednisolone and medroxyprogesterone on corneal wound healing, ulceration, and neovascularization . Arch Ophthalmol 1983; 101:640-643.Crossref 16. Deutsch TA, Hughes WF: Suppressive effects of indomethacin on thermally induced neovascularization of rabbit corneas . Am J Ophthalmol 1979;87:536-540. 17. Cooper CA, Bergamini MVW, Leopold IH: Use of flurbiprofen to inhibit corneal neovascularization . Arch Ophthalmol 1980;98:1102-1105.Crossref 18. Sholley MM, Gimbrone MA Jr, Cotran RS: The effects of leukocyte depletion on corneal neovascularization . Lab Invest 1978;38:32-40.Crossref 19. Kulkarni PS, Bhattacherjee P, Eakins KE, et al: Anti-inflammatory effects of betamethasone phosphate, dexamethasone phosphate and indomethacin on rabbit ocular inflammation induced by bovine serum albumin . Curr Eye Res 1981;1:43-47.Crossref 20. Eakins KE: Prostaglandin and non-prostaglandin mediated breakdown of the blood-aqueous barrier . Exp Eye Res 1977;25( (suppl) ):483-489.Crossref 21. Kulkarni PS, Srinivasan BD: The effect of intravitreal and topical prostaglandins on intraocular inflammation . Invest Ophthalmol Vis Sci 1982;23:383-392. 22. Higgs GA, McCall E, Youlten LJF: A chemotactic role for prostaglandins released from polymorphonuclear leucocytes during phagocytosis . Br J Pharmacol 1975;53:539-546.Crossref 23. Adams SS, Burrows CA, Skeldon N, et al: Inhibition of prostaglandin synthesis and leucocyte migration by flurbiprofen . Curr Med Res Opin 1977;5:11-16.Crossref 24. Bray MA, Franco M: Prostaglandins and inflammatory cell movement in vitro . Int Arch Allergy Appl Immunol 1978;56:500-506.Crossref 25. Shibuya E, Masuda K, Izawa Y: Effects of prostaglandins on leukocyte migration . Prostaglandins 1976;12:165-174.Crossref 26. Walker JR, Smith MJH, Ford-Hutchinson AW: Prostaglandins and leucotaxis . J Pharm Pharmacol 1976;28:745-747.Crossref 27. Chang J, Lewis GP, Piper PJ: The effect of anti-inflammatory drugs on the prostaglandin system in human subcutaneous adipose tissue . Br J Ophthalmol 1977;61:446-447.Crossref 28. Chandrabose KA, Lapetina EG, Schmitges CJ, et al: Action of corticosteroids in regulation of prostaglandin synthesis . Proc Natl Acad Sci USA 1978;75:214-217.Crossref 29. Kulkarni PS, Srinivasan BD: Steroidal and nonsteroidal anti-inflammatory drugs in ocular inflammation . Ocular Inflammation Ther 1983; 1:11-18. 30. Duffin RM, Weissman BA, Glasser DB, et al: Flurbiprofen in the treatment of corneal neovascularization induced by contact lenses . Am J Ophthalmol 1982;93:607-614. 31. Jaffe EB, Podos SM, Becker B: Indomethacin blocks arachidonic acid associated elevations of aqueous humor prostaglandin E . Invest Ophthalmol Vis Sci 1973;12:621-622. 32. Podos SM: Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease . Trans Am Ophthalmol Soc 1977;74:637-660. 33. Hanna C, Keatts HC: Indomethacin in ocular inflammation in the rabbit . Arch Ophthalmol 1967;99:681-682. 34. Miller D, Gruenberg P, Miller R, et al: Topical flurbiprofen or prednisolone: Effect on corneal wound healing in rabbits . Arch Ophthalmol 1981;99:681-682.Crossref 35. Srinivasan BD, Kulkarni PS: Polymorphonuclear leukocyte response: Inhibition following corneal epithelial denudation by steroidal and nonsteroidal anti-inflammatory agents . Arch Ophthalmol 1981;99:1085-1089.Crossref

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Feb 1, 1985

References

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