PMID- 8550317
OWN - NLM
STAT- MEDLINE
DCOM- 19960216
LR  - 20131121
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 37
IP  - 1
DP  - 1996 Jan
TI  - Enhanced prostaglandin synthesis after ultraviolet-B exposure modulates DNA 
      synthesis of lens epithelial cells and lowers intraocular pressure in vivo.
PG  - 142-53
AB  - PURPOSE: To study the functional significance of prostaglandin synthesis after 
      ultraviolet-B (UVB) exposure of cultured human lens epithelial cells and rabbit 
      eyes in vivo. METHODS: Prostaglandin E2 (PGE2) was assayed using a 
      radioimmunoassay (RIA) and mass spectroscopy. An immortalized human lens 
      epithelial cell line (HLE-B3) was exposed to UV irradiation, and the synthesis of 
      PGE2 was compared with the rabbit lens epithelial cell line N/N1003A. Intact 
      human lenses were exposed to UVB in organ culture. [3H]Thymidine incorporation 
      was measured in cultured lens epithelial cells by incubation with the radiolabel. 
      The effects of isobutyl methyl xanthine (IBMX), an inhibitor of phosphodiesterase 
      and of dibutyryl cyclic adenosine monophosphate (cAMP), an analog of cAMP, on 
      PGE2 synthesis and DNA synthesis, were determined. Rabbit eyes were exposed to 
      UVB radiation in vivo. Intraocular pressure was measured at specific times after 
      exposure. Aqueous humor was remove from rabbit eyes, and its PGE2 content was 
      measured by RIA. RESULTS: Cultured human lens epithelial cells (HLE), like rabbit 
      lens epithelial cells (RLE), showed a dose-dependent increase in basal PGE2 
      synthesis 24 hours after UVB exposure. However, the amount of PGE2 synthesis was 
      2000-fold higher in the rabbit cells. Ultraviolet-B radiation enhanced the 
      incorporation of [3H]thymidine in lens epithelial cells. Pretreatment of cells 
      with indomethacin reduce PGE2 synthesis and [3H]thymidine incorporation. The 
      human and rabbit cells responded in a similar manner to changes in DNA synthesis 
      after UVB exposure. The addition of IBMX or dbcAMP to indomethacin-treated, 
      UVB-exposed cells restored DNA synthesis toward the levels observed in the 
      UVB-exposed cells. An increase in the concentration of cAMP was observed in lens 
      epithelial cells exposed to exogenous PGE2. PGE2 synthesis in intact human lenses 
      also increased twofold 24 hours after UVB exposure. Exposure of the rabbit eye in 
      vivo to an optimal dose of UVB produced an increase in the PGE2 levels of the 
      lens and the aqueous humor. Measurements of the intraocular pressure (IOP) of the 
      animals showed a decrease in IOP by 2.21 +/- 0.66 and 6.45 +/- 0.79 mm Hg (mean 
      +/- SEM, P = 0.004, t-test) at 6 and 24 hours after UVB exposure, respectively. 
      The decrease in IOP was prevented by pretreatment with indomethacin. Exposure of 
      the rabbit lens to UVB radiation in vivo enhanced [3H]thymidine incorporation 
      twofold into the lens. Pretreatment of rabbits with indomethacin before exposure 
      reduced this response. CONCLUSIONS: Results indicate that UVB exposure enhances 
      PGE2 synthesis in HLE cultures as well as in rabbit lenses irradiated in vivo. 
      This increased PGE2 synthesis is related to the increase in DNA synthesis 
      observed after UVB treatment. The modulation of DNA synthesis in cultured lens 
      epithelial cells after UVB exposure may be mediated by a cAMP-dependent 
      mechanism.
FAU - Andley, U P
AU  - Andley UP
AD  - Department of Ophthalmology and Visual Sciences, Washington University School of 
      Medicine, St. Louis, Missouri 63110, USA.
FAU - Becker, B
AU  - Becker B
FAU - Hebert, J S
AU  - Hebert JS
FAU - Reddan, J R
AU  - Reddan JR
FAU - Morrison, A R
AU  - Morrison AR
FAU - Pentland, A P
AU  - Pentland AP
LA  - eng
GR  - EY00362/EY/NEI NIH HHS/United States
GR  - EY02687/EY/NEI NIH HHS/United States
GR  - EY05681/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 9007-49-2 (DNA)
RN  - E0399OZS9N (Cyclic AMP)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - TBT296U68M (1-Methyl-3-isobutylxanthine)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - 1-Methyl-3-isobutylxanthine/pharmacology
MH  - Animals
MH  - Autoradiography
MH  - Cell Division/radiation effects
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cyclic AMP/metabolism
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - DNA/*biosynthesis/radiation effects
MH  - DNA Replication/radiation effects
MH  - Dinoprostone/*biosynthesis/radiation effects
MH  - Dose-Response Relationship, Radiation
MH  - Epithelium/drug effects/radiation effects
MH  - Humans
MH  - Indomethacin/pharmacology
MH  - Infant
MH  - Intraocular Pressure/*radiation effects
MH  - Lens, Crystalline/cytology/drug effects/*radiation effects
MH  - Mass Spectrometry
MH  - Ocular Hypertension/etiology
MH  - Phosphodiesterase Inhibitors/pharmacology
MH  - Rabbits
MH  - Radioimmunoassay
MH  - *Ultraviolet Rays
EDAT- 1996/01/01 00:00
MHDA- 1996/01/01 00:01
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 1996/01/01 00:01 [medline]
PHST- 1996/01/01 00:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 1996 Jan;37(1):142-53.