Age-related cataract: Antibodies against lens antigens, plus inhibitory cytokine, killed mouse lens epithelial cells in vitro

T. Shinohara, D. P. Singh, T. Sueno, N. Ibaraki, V. N. Reddy, L. T. Chylack

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Circulating autoantibodies (auto-Ab) against lens antigens (Ag) are highly prevalent in patients with cataract, but their pathogenic significance is unknown. We hypothesize that auto-Ab and certain inhibitory cytokines may be pathogenic agents capable of damaging lens epithelial cells (LECs). Methods: To test this hypothesis, we incubated LECs with guinea-pig complement, various cytokines, and mouse Abs against β-crystallins. Human sera from cataract patients were used also. Cidal assay: trypan blue exclusion. Results: We found that Ab was bound to mouse LECs (MLECs), and the cells were killed by the Ab in the presence of complement. Stationary cells were killed more often than actively growing cells. Sera obtained from cataract patients also killed MLECs in culture. Human sera in which complement was heat-inactivated did not affect the MLECs, but killed MLECs when guinea-pig complement was added. Inhibitory cytokines such as TGF-β and granulocyte-macrophage colony stimulating factors (GM-CSFs) inhibited cell growth and transformed cells into a stationary phase. The cidal effect on LECs was most pronounced with TGF-β and Abs against β-crystallins. Conclusions: These results support the hypothesis that auto-Abs against lens Ags are cidal to MLECs. Cell death may involve the complement-mediated pathway. Furthermore, Ab plus certain cytokines (TGF-βs and GM-CSFs) may damage LECs without noticeable ocular inflammation.

Original languageEnglish (US)
Pages (from-to)S1142
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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