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LOXL1 expression in lens capsule tissue specimens from individuals with pseudoexfoliation syndrome and glaucoma.

Publication ,  Journal Article
Khan, TT; Li, G; Navarro, ID; Kastury, RD; Zeil, CJ; Semchyshyn, TM; Moya, FJ; Epstein, DL; Gonzalez, P; Challa, P
Published in: Mol Vis
November 2, 2010

PURPOSE: To study lysyl oxidase-like 1 (LOXL1) expression in freshly collected lens capsules from pseudoexfoliation syndrome (XFS), pseudoexfoliation glaucoma (XFG), and normal cataract control individuals. We also investigated the effects of four glaucoma drug medications on LOXL1 expression in primary human lens epithelial cell cultures to see if they could affect LOXL1 expression. METHODS: Lens capsules were collected at the time of cataract surgery. Controls were matched to age, sex, and ethnicity. Total RNA was isolated from individual lens capsule samples and real-time PCR was performed on each sample using primers flanking the sixth exon of the LOXL1 gene. Cell cultures were grown to confluence in four separate six-well plates at 37 °C in 5% CO2. Each plate was then treated with one of four different glaucoma drugs (brinzolamide 1%, brimonidine tartrate 0.1%, timolol maleate 0.5%, and latanoprost 0.005%) once daily for seven days (at both 1:1,000 and 1:100 concentrations relative to media). Controls were not treated with any drug but media was changed in the same manner. After one week of treatment, cells were harvested and total RNA isolated. Real-time PCR was performed on each group of cells. RESULTS: Seven XFS, seven XFG, and ten cataract control specimens were analyzed. LOXL1 expression was detected in the lens capsule specimens from each of the four groups. Significant expression differences were found between the control and XFG groups and XFS and XFG groups. No significant difference was observed between the control and XFS group. No significant decrease in LOXL1 expression was seen with drug incubation of the four medications (Brinzolamide, Timolol, Latanoprost, and Brimonidine) at the 1:1,000 drug:media concentrations versus controls. At 10-fold higher concentrations (1:100 drug:media), brinzolamide, timolol maleate, and latanoprost showed small increases in LOXL1 expression relative to controls. This effect was not observed with brimonidine tartrate. CONCLUSIONS: These results establish that LOXL1 expression is reduced in lens capsule specimens from XFG individuals but not XFS. The drug treatment incubation studies suggest that the change in LOXL1 expression observed in XFG is not attributable to glaucoma drug therapy. If a causative functional relationship can be validated, modification of LOXL1 expression in affected tissues may represent a novel treatment strategy for this disorder.

Duke Scholars

Published In

Mol Vis

EISSN

1090-0535

Publication Date

November 2, 2010

Volume

16

Start / End Page

2236 / 2241

Location

United States

Related Subject Headings

  • Ophthalmology & Optometry
  • Middle Aged
  • Male
  • Lens Capsule, Crystalline
  • Humans
  • Glaucoma
  • Gene Expression Regulation, Enzymologic
  • Female
  • Exfoliation Syndrome
  • Epithelial Cells
 

Citation

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Khan, T. T., Li, G., Navarro, I. D., Kastury, R. D., Zeil, C. J., Semchyshyn, T. M., … Challa, P. (2010). LOXL1 expression in lens capsule tissue specimens from individuals with pseudoexfoliation syndrome and glaucoma. Mol Vis, 16, 2236–2241.
Khan, Tanya T., Guorong Li, Iris D. Navarro, Rama D. Kastury, Carol J. Zeil, Taras M. Semchyshyn, Frank J. Moya, David L. Epstein, Pedro Gonzalez, and Pratap Challa. “LOXL1 expression in lens capsule tissue specimens from individuals with pseudoexfoliation syndrome and glaucoma.Mol Vis 16 (November 2, 2010): 2236–41.
Khan TT, Li G, Navarro ID, Kastury RD, Zeil CJ, Semchyshyn TM, et al. LOXL1 expression in lens capsule tissue specimens from individuals with pseudoexfoliation syndrome and glaucoma. Mol Vis. 2010 Nov 2;16:2236–41.
Khan TT, Li G, Navarro ID, Kastury RD, Zeil CJ, Semchyshyn TM, Moya FJ, Epstein DL, Gonzalez P, Challa P. LOXL1 expression in lens capsule tissue specimens from individuals with pseudoexfoliation syndrome and glaucoma. Mol Vis. 2010 Nov 2;16:2236–2241.

Published In

Mol Vis

EISSN

1090-0535

Publication Date

November 2, 2010

Volume

16

Start / End Page

2236 / 2241

Location

United States

Related Subject Headings

  • Ophthalmology & Optometry
  • Middle Aged
  • Male
  • Lens Capsule, Crystalline
  • Humans
  • Glaucoma
  • Gene Expression Regulation, Enzymologic
  • Female
  • Exfoliation Syndrome
  • Epithelial Cells