title: Cosmetic preservatives as therapeutic corneal and scleral tissue cross-linking agents.
abstract: OBJECTIVE
  Previously, aliphatic β-nitroalcohols (BNAs) have been studied as a means to chemically induce tissue cross-linking (TXL) of cornea and sclera. There are a number of related and possibly more potent agents, known as formaldehyde releasers (FARs), that are in commercial use as preservatives in cosmetics and other personal care products. The present study was undertaken in order to screen such compounds for potential clinical utility as therapeutic TXL agents.
  
  
  METHODS
  A chemical registry of 62 FARs was created from a literature review and included characteristics relevant to TXL such as molecular weight, carcinogenicity/mutagenicity, toxicity, hydrophobicity, and commercial availability. From this registry, five compounds [diazolidinyl urea (DAU), imidazolidinyl urea (IMU), sodium hydroxymethylglycinate (SMG), DMDM hydantoin (DMDM), 5-Ethyl-3,7-dioxa-1-azabicyclo [3.3.0] octane (OCT)] were selected for efficacy screening using two independent systems, an ex vivo rabbit corneal cross-linking simulation setup and incubation of cut scleral tissue pieces. Treatments were conducted at pH 7.4 or 8.5 for 30 minutes. Efficacy was evaluated using thermal denaturation temperature (Tm), and cell toxicity was studied using the trypan blue exclusion method.
  
  
  RESULTS
  Cross-linking effects in the five selected FARs were pH and concentration dependent. Overall, the Tm shifts were in agreement with both cornea and sclera. By comparison with BNAs previously reported upon, the FARs identified in this study were significantly more potent but with similar or better cytotoxicity.
  
  
  CONCLUSIONS
  The FARs, a class of compounds well known to the cosmetic industry, may have utility as therapeutic TXL agents. The compounds studied thus far show promise and will be further tested.
authors: Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, New York, United States.
authors: Natasha
authors: N
authors: Babar
authors: Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, New York, United States.
authors: MiJung
authors: M
authors: Kim
authors: Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, New York, United States.
authors: Kerry
authors: K
authors: Cao
authors: Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, New York, United States.
authors: Yukari
authors: Y
authors: Shimizu
authors: Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, New York, United States.
authors: Su-Young
authors: SY
authors: Kim
authors: Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, New York, United States.
authors: Anna
authors: A
authors: Takaoka
authors: Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, New York, United States.
authors: Stephen L
authors: SL
authors: Trokel
authors: Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, New York, United States.
authors: David C
authors: DC
authors: Paik
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D003124:Colorimetry; D003315:Cornea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004195:Disease Models, Animal; D007640:Keratoconus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D011817:Rabbits; D012590:Sclera / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D046509:Tissue Culture Techniques
chemical_list: D003432:Cross-Linking Reagents; D011310:Preservatives, Pharmaceutical; D003094:Collagen
keywords: cornea; keratoconus; progressive myopia; sclera; tissue cross-linking
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