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Regulation of Cataractogenesis in Cultured Bovine Lenses by ATB 343
Author(s) -
Maffofou Leonce N,
SegewkalHeruye Segewkal H,
NjieMbye Ya Fatou,
Ohia Sunny E,
Opere Catherine A.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.812.8
Subject(s) - chemistry , ascorbic acid , in vivo , bovine serum albumin , endogeny , lens (geology) , biochemistry , optics , biology , food science , microbiology and biotechnology , physics
Purpose There is evidence that substrates for the endogenous production of hydrogen sulfide (H 2 S) such as L‐cysteine and N‐acetylcysteine ( Zhang et al., Mol Vis, 14:862–870, 2008) and NSAIDs such as ibuprofen ( Robert and Harding, Exp Eye Res, 54:509–518) can mitigate cataractogenesis in vitro and in vivo . However, the role of the hybrid compound consisting of the NSAID, indomethacin and a H 2 S‐donating moiety, ATB 343 on cataractogenesis has not been elucidated. In this study, we investigated the effect of the ATB 343 on cataractogenesis in cultured bovine lenses. Methods Freshly isolated bovine lenses were cultured in a DMEM buffer solution as follows: Group I: Control (DMEM); Group II–III: H 2 O 2 (10 mM or 50 mM); Group IV–VI: ATB 343 (10 −8 M to 10 −6 M; Group VII: ascorbic acid (AA; 10 mM) in presence and absence of H 2 O 2 (10 mM or 50 mM). Lenses were incubated in a CO 2 chamber and assessed at 3, 6, 24, 48 and 72 hour‐time points. Qualitative assessments were conducted by visual inspection of lenses and photographic images captured against a black grid, while quantitative assessment was conducted by measurement of transmittance using a plate reader (Synergy H1 hybrid reader; Bio Tek Instruments, Inc) at every time point. Results DMEM‐cultured lenses exhibited a time‐dependent decrease in transmittance (420nm) and a corresponding loss of lens optical clarity up to 72 hours. Similar to the endogenous antioxidant, AA (10 mM), ATB 343 (10 −7 M) attenuated time‐dependent lens degradation up to 24 hours. H 2 O 2 (10 mM and 50 mM) decreased light transmittance in a time‐dependent manner, achieving an inhibition of 41.98% (n=12; p<0.0001) and 46.37% (n=12; p<0.0001), respectively after 72 hours. Interestingly, ATB 343 (10 −8 M to 10 −6 M) partially reversed H 2 O 2 (10 mM)‐induced degradation up to 72 hours. After 48 hours, the rank order of protection was: ATB (10 −7 M)>ATB (10 −6 M)>AA (10 mM)>ATB (10 −8 M). Similarly, ATB 343 (10 −7 M and 10 −6 M) partially reversed H 2 O 2 (50 mM)‐induced lens degradation up to 48 hours. After 24 hours, the rank order of protection was: ATB (10 −7 M)>ATB (10 −8 M)>ATB (10 −6 M >AA (10 mM). Conclusion ATB 343 protected cultured lenses from time‐dependent degradation up to 24 hours and partially protected cultured bovine lenses from H 2 O 2 ‐induced cataractogenesis. Support or Funding Information Creighton University‐SPAHP, Pharmaceutical Sciences Graduate Program This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .