BACTERIOCHLOROPHYLL DERIVATIVE WST11/NIR

Riboflavin/UVA collagen cross-linking has several drawbacks including the lengthy riboflavin treatment time, the prolonged exposure to UV irradiation and toxicity to keratocytes and corneal endothelial cells [1,2], so alternative corneal stiffening treatments, that are potentially safer for the patient, are currently being sought.

One possibility is photochemical corneal stiffening by topical application of a novel photosensitizer referred to as WST11 followed by near infrared (NIR, 755nm) illumination [3]. WST11, or  palladium bacteriochlorin 130-(2-sulfoethyl) amide dipotassium salt,  is a synthesized chemical derivative of a photosynthetic pigment that generates oxygen radicals (O2and •OH) after illumination with non-hazardous NIR [4,5]. One role of these photogenerated radicals is thought to be in promoting protein cross-linking [6] and, therefore, their  topical application on the cornea should result in stiffening for the treatment of keratoconus and related pathologies.

The treatment of rabbit corneas with WST11/NIR has been shown to increase corneal biomechanical strength without generating singlet oxygen in the cornea [3]. When the WST11 was formulated with dextran T500 (WST-D) the treatment resulted in significant corneal stiffening   whilst causing fewer detrimental effects (reduced post-treatment oedema and faster epithelial healing) [3].

[1] Wollensak, G. et al. Keratocyte cytotoxicity of riboflavin/UVA-treatment in vitro. Eye. 2004;18:718–722.

[2] Wollensak, G. Histological changes in human cornea after cross-linking with riboflavin and ultraviolet A [letter]. Acta Ophthalmol. 2010;88:e17–e18.

[3] Marcovich, A. L. et al. Stiffening of rabbit corneas by the bacteriochlorophyll derivative WST11 using near infrared light. Invest Ophthalmol Vis Sci. 2012;53:6378-88.

[4] Ashur, I. et al. Photocatalytic generation of oxygen radicals by the water-soluble bacteriochlorophyll derivative WST11, noncovalently bound to serum albumin. J Phys Chem. 2009;113:8027–8037.

[5] Mazor, O. et al. WST11, a novel watersoluble bacteriochlorophyll derivative; cellular uptake, pharmacokinetics, biodistribution, and vascular targeted photodynamic activity against melanoma tumors. Photochem Photobiol. 2005;81:342–345.

[6] Liu, K. et al. Superoxide, hydrogen peroxide and hydroxyl radical in D1/D2/cytochrome b-559 Photosystem II reaction center complex. Photosynth Res. 2004;81:41–47.