Results obtained by our research group during the last grant period suggest that PGs may play an important role in lens pathophysiology and implicates lens PG biosynthesis with development of cataract. However, it is unclear how manipulation of lens PG levels could modulate lens function to maintain lens transparency. Aspirin-like drugs, which inhibit PG synthesis, delay human cataract development. Our published reports indicate that a decreased PG synthesis is also associated with the development of galactose induced cataractogenesis. This proposal will examine the discrepancy in relating PG synthesis to development of cataract and determine the physiological role of PGs in lens development. Different models of cataract production (eg. streptozotocin and x- irradiation) will be used to determine if altered lens PG biosynthesis is a common feature in cataract. The leukotrienes, like the PGs may also play a role in the physiology of the lens. The relevance of our findings is limited until we understand the role of eicosanoids in modulating lens physiological functions and concomitantly whether the human lens can generate PGs. This study will examine the role of eicosanoid production in development, aging and cataractogenesis using biochemical, pharmacological, microchemical and tissue culture techniques. The role oftens PGs in mitosis, cyclic nucleotide metabolism, and ion transport will be examined in both young and old rats, as will the effects of PG inhibitors in modifying lens cellular function and cataract onset. The ability to regulate lens eicoanoid synthesis might, in the long term, lead to a rational therapy for delaying the onset of human cataract.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Visual Sciences B Study Section (VISB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Medicine & Dentistry of NJ
Schools of Medicine
United States
Zip Code
Jaya, B; Hu, L; Bauman, J W et al. (1993) Effect of galactose regimen on glomerular heparan sulfate synthesis and albumin excretion in diabetic rats. Res Commun Chem Pathol Pharmacol 80:143-52
Lysz, T W; Lin, C; Fu, S C et al. (1992) Temporal and regional production of 12(S)hydroxyeicosatetraenoic acid [12(S)-HETE] in rat lens. Exp Eye Res 54:769-74
Lysz, T W; Wu, Y; Brash, A et al. (1991) Identification of 12(S)-hydroxyeicosatetraenoic acid in the young rat lens. Curr Eye Res 10:331-7
Lysz, T W; Billiar, T R; Curran, R D et al. (1990) Kupffer cell-hepatocyte interactions and the changes in 1-14C-arachidonate incorporation in response to endotoxin in vitro. Prostaglandins 39:497-514
Lysz, T W; Zweig, A; Keeting, P E (1988) Examination of mouse and rat tissues for evidence of dual forms of the fatty acid cyclooxygenase. Biochem Pharmacol 37:921-7
Keeting, P E; Dong, D S; Fu, S C et al. (1987) Rat lens prostaglandin generation proceeds by the non-enzymatic degradation of PGH2 endoperoxide. Exp Eye Res 44:261-8
Keeting, P E; Dong, D S; Lysz, T W et al. (1986) Rat lens prostaglandin biosynthesis during galactose-induced cataractogenesis. Exp Eye Res 43:1103-10