Investigative Ophthalmology & Visual Science, Vol 27, 926-931, Copyright © 1986 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Role of leukocytes in ocular inflammation of tyrosinemia II

RE Ripple, KM Lohr, SS Twining, RA Hyndiuk and JG Caya

In the animal model of tyrosinemia II only corneas from tyrosine(tyr)- fed rats produce chemoattractants in organ culture. To study the role of neutrophils (PMNs) in production of these chemoattractants, leukocytes (WBCs) were depleted using i.p. cyclophosphamide (CP). Saline (SAL)-treated rats maintained 18,375 +/- 894 WBC/mm3 (mean +/- SEM) with 4168 +/- 424 PMNs. Rats receiving CP (150 mg/kg day 0, 75 mg/kg day 4) has 1565 +/- 170 WBC (565 +/- 129 PMN) on day 3, and 398 +/- 68 WBC (19 +/- 5 PMN) on day 8. Rats ate a low-protein +/- 5% tyr diet on days 4-8. Only SAL-treated tyr-fed rats developed plaque-like gray epithelial lesions; histopathology showed corneal epithelial necrosis, stromal edema, and epithelial and stromal PMN infiltration. Control and CP-treated tyr-fed rat corneas showed no inflammation. On day 8 corneas were cultured in RPMI 1640 + 5% heat-inactivated fetal bovine serum. After 3 days, supernatants were assayed for chemotactic activity (leading front method); data were expressed as the percentage of peritoneal PMN migration relative to 5% zymosan-activated rat serum. The mean total migration toward 75% supernatant from SAL-treated, tyr- fed rat corneas was 79%, whereas migration toward corneal supernatants from controls and CP-treated tyr-fed rats ranged from 42-48%. Corneal extracts were assayed for proteolytic activity. WBC depletion prevented the increase in cathepsin B- and D-like activities present in tyr-fed corneas, suggesting that PMNs were a major source of these enzymes. The data suggest that WBC depletion reduces both corneal inflammation in vivo and the production of chemotactic activity by tyr-fed corneas in culture.