Safety testing of indocyanine green in an ex vivo porcine retina model.
OBJECTIVE
To assess retinal toxicity of indocyanine green (ICG) in a porcine ex vivo perfusion organ culture model, and to measure intraretinal penetration of ICG applied to the retinal surface.


METHODS
The retinal surface of fresh porcine retinal tissue was exposed to ICG 0.1% and 1% dissolved in glucose 5% for 1 and 30 minutes with and without concomitant illumination. Specimens were then kept in perfusion organ culture for 24 hours before examination by light microscopy and the TUNEL technique. Tissue samples treated with DNAse served as positive controls, and samples exposed to saline served as negative controls. Fluorescence microscopy was used to localize ICG at 1 minute, 60 minutes, 2 hours, and 3 hours after a 1-minute exposure of the retinal surface to ICG 1%.


RESULTS
No increase in TUNEL-positive cells was observed after exposure to ICG 0.1% for 1 minute. Moderate apoptosis was found after 1-minute exposure to ICG 1% and 30-minute exposure to ICG 0.1%, and severe apoptosis was found after 30-minute exposure to ICG 1%. Concomitant application of light did not influence the degree of apoptosis. No signs of cell necrosis were found. After 1-minute exposure of the retinal surface, ICG 1% gradually penetrated the entire retina.


CONCLUSIONS
ICG induced apoptosis but not necrosis in all nuclear retinal layers in a dose-dependent manner. Brief exposure to ICG 0.1% for 1 minute and illumination for 3 minutes simulated the intraoperative use of ICG. No retinal apoptosis or necrosis was observed. ICG briefly applied to the retinal surface gradually penetrated the entire retina.
Saikia
Parykshit
P
Department of Ophthalmology, University of Regensburg, Franz-Josef-Strauss Allee 11, D-93042 Regensburg, Germany.
Maisch
Tim
T
Kobuch
Karin
K
Jackson
Timothy L
TL
Bäumler
Wolfgang
W
Szeimies
Rolf-Markus
RM
Gabel
Veit-Peter
VP
Hillenkamp
Jost
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004396:Coloring Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D020287:In Situ Nick-End Labeling; D007208:Indocyanine Green / Q000493:pharmacokinetics / Q000633:toxicity*; D008027:Light; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D009336:Necrosis; D009924:Organ Culture Techniques; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D013552:Swine
D004396:Coloring Agents; D007208:Indocyanine Green