Investigating retinal toxicity of a lutein-based dye in a model of isolated and perfused bovine retina
- 16 Downloads
Retidyne™ is a new lutein-based dye for internal limiting membrane staining. It uses the intrinsic staining characteristics of lutein which is already known to act as an antioxidant and blue-light filter in the human retina. We investigated retinal tolerance to different staining times measured by the electroretinogram (ERG) of an isolated and perfused retina whole mount.
For functionality, testing bovine retinas were prepared and perfused with an oxygen saturated standard solution and the ERG was recorded until stable b-wave amplitudes were reached. Then the perfusion was stopped and Retidyne™ was applied directly onto the retinal surface for exposure times of 60 or 120 s. After restarting the perfusion with standard solution, the ERG amplitudes were monitored for 75 min. To investigate the effects on photoreceptor function alone, 1 mM asparate was added to block b-waves.
For an exposure time of 60 s amplitudes of a- and b-waves remained stable throughout the experiment. Exposure times of 120 s caused an initial drop of amplitudes that reached statistical significance only for a-waves (a, − 21%, p = 0.047; b, − 14%, p = 0.052). This effect was only seen during the first minutes of the washout and the ERG recovered completely.
In the model of isolated and perfused bovine retina, Retidyne™ showed a good safety profile for common intraoperatively used staining times. An initial toxic effect regarding the transient drop of amplitudes cannot be ruled out but the effect might also be explained by the partial blockage of the flashlight due to a more intense staining effect at the beginning of the washout.
KeywordsLutein Vital dye Internal limiting membrane staining Peeling surgery Electroretinogram Biocompatibility
Compliance with ethical standards
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Luke J, Ludeke I, Acksteiner A, Nassar K, Hoerauf H, Grisanti S, Luke M (2013) Morphological and functional outcome after brilliant blue G-assisted macular hole surgery. Ophthalmologica Journal international d’ophtalmologie International journal of ophthalmology Zeitschrift fur Augenheilkunde 230(2):81–86. https://doi.org/10.1159/000351658 CrossRefGoogle Scholar
- 9.Narayanan R, Kenney MC, Kamjoo S, Trinh TH, Seigel GM, Resende GP, Kuppermann BD (2005) Toxicity of indocyanine green (ICG) in combination with light on retinal pigment epithelial cells and neurosensory retinal cells. Curr Eye Res 30(6):471–478. https://doi.org/10.1080/02713680590959312 CrossRefGoogle Scholar
- 10.Kernt M, Hirneiss C, Wolf A, Liegl R, Rueping J, Neubauer A, Alge C, Ulbig M, Gandorfer A, Kampik A, Haritoglou C (2012) Indocyanine green increases light-induced oxidative stress, senescence, and matrix metalloproteinases 1 and 3 in human RPE cells. Acta Ophthalmol 90(6):571–579. https://doi.org/10.1111/j.1755-3768.2010.01961.x CrossRefGoogle Scholar
- 14.Yu CC, Nandrot EF, Dun Y, Finnemann SC (2012) Dietary antioxidants prevent age-related retinal pigment epithelium actin damage and blindness in mice lacking alphavbeta5 integrin. Free Radic Biol Med 52(3):660–670. https://doi.org/10.1016/j.freeradbiomed.2011.11.021 CrossRefGoogle Scholar
- 17.Badaro E, Furlani B, Prazeres J, Maia M, Lima AA, Souza-Martins D, Muccioli C, Lucatto LF, Belfort R Jr (2014) Soluble lutein in combination with brilliant blue as a new dye for chromovitrectomy. Graefes Arch Clin Exp Ophthalmol 252(7):1071–1078. https://doi.org/10.1007/s00417-013-2539-5 CrossRefGoogle Scholar
- 18.Luke M, Weiergraber M, Brand C, Siapich SA, Banat M, Hescheler J, Luke C, Schneider T (2005) The isolated perfused bovine retina--a sensitive tool for pharmacological research on retinal function. Brain Res Brain Res Protoc 16(1–3):27–36. https://doi.org/10.1016/j.brainresprot.2005.09.001 CrossRefGoogle Scholar
- 19.Sickel W (1966) The isolated retina maintained in a circulating medium. Combined optical and electrical investigations of metabolic aspects of the generation of the electroretinogram. In: Clinical electroretinography. Pergamon Press, Oxford, pp 115–124Google Scholar
- 22.Rodrigues EB, Meyer CH (2008) Meta-analysis of chromovitrectomy with indocyanine green in macular hole surgery. Ophthalmologica Journal international d’ophtalmologie International journal of ophthalmology Zeitschrift fur Augenheilkunde 222(2):123–129. https://doi.org/10.1159/000112630 CrossRefGoogle Scholar
- 25.Tura A, Alt A, Haritoglou C, Meyer CH, Schneider T, Grisanti S, Luke J, Luke M, International Chromovitrectomy C (2014) Testing the effects of the dye acid violet-17 on retinal function for an intraocular application in vitreo-retinal surgery. Graefes Arch Clin Exp Ophthalmol 252(12):1927–1937. https://doi.org/10.1007/s00417-014-2761-9 CrossRefGoogle Scholar
- 29.Furlani BA, Barroso L, Sousa-Martins D, Maia M, Moraes-Filho MN, Badaro E, Portella R, Lima-Filho AA, Rodrigues EB, Belfort R Jr (2014) Lutein and zeaxanthin toxicity with and without brilliant blue in rabbits. J Ocul Pharmacol Ther 30(7):559–566. https://doi.org/10.1089/jop.2013.0171 CrossRefGoogle Scholar
- 30.Casaroli-Marano RP, Sousa-Martins D, Martinez-Conesa EM, Badaro E, Nunes RP, Lima-Filho AA, Rodrigues EB, Belfort R Jr, Maia M (2015) Dye solutions based on lutein and zeaxanthin: in vitro and in vivo analysis of ocular toxicity profiles. Curr Eye Res 40(7):707–718. https://doi.org/10.3109/02713683.2014.952831 CrossRefGoogle Scholar
- 31.Henrich PB, Haritoglou C, Meyer P, Ferreira PR, Schotzau A, Katamay R, Josifova T, Schneider U, Flammer J, Priglinger S (2010) Anatomical and functional outcome in Brilliant Blue G assisted chromovitrectomy. Acta Ophthalmol 88(5):588–593. https://doi.org/10.1111/j.1755-3768.2008.01477.x CrossRefGoogle Scholar
- 32.Hoing A, Remy M, Dirisamer M, Priglinger S, Schonfeld CL, Kampik A, Haritoglou C (2011) An in-vivo evaluation of Brilliant Blue G in macular surgery. Klin Monatsbl Augenheilkd 228(8):724–728. https://doi.org/10.1055/s-0031-1273351 [doi]
- 33.Mansoor S, Sharma A, Caceres-Del-Carpio J, Zacharias LC, Patil AJ, Gupta N, Limb GA, Kenney MC, Kuppermann BD (2015) Effects of light on retinal pigment epithelial cells, neurosensory retinal cells and Muller cells treated with Brilliant Blue G. Clin Exp Ophthalmol 43(9):820–829. https://doi.org/10.1111/ceo.12568 CrossRefGoogle Scholar