Intravitreal thalidomide reduces experimental preretinal neovascularisation without induction of retinal toxicity.
OBJECTIVE
Proliferative retinopathies remain the most common causes of blindness. Retinal neovascularisation is induced by hypoxic upregulation of angiogenic growth factors, such as vascular endothelial growth factor (VEGF). Thalidomide has been shown to be anti-angiogenic via reduction of VEGF levels. We investigated the effect of intravitreal application of thalidomide on neovascularisation and retinal toxicity in a mouse model of proliferative retinopathy.


METHODS
C57BL/6J mice were exposed to 75% oxygen from postnatal day (p) 7 to p12. Immediately after transfer to room air at p12, mice received an intravitreal injection of 150 microg/microl thalidomide or control solution. Preretinal neovascularisation was quantified at p17. VEGF levels were assessed in whole retinal lysates at p13 and p17. Retinal toxicity was assessed by measuring retinal layer thickness and by analysing caspase-3 activity and apoptotic cell counts in retinal layers to examine retinal apoptosis.


RESULTS
Intravitreal application of thalidomide significantly reduced preretinal neovascularisation by 62% compared with control treated contralateral eyes (p=0.01). Interestingly, this effect was established without a change in retinal VEGF levels. Intravitreal thalidomide was not toxic, as retinal layer thickness, retinal caspase-3 activity and apoptotic cell counts were unaltered.


CONCLUSIONS
These data indicate that intravitreal application of thalidomide can be an effective and safe way to treat retinal neovascularisation.
Vom Hagen
Franziska
F
5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
Kamppeter
Bernd A
BA
Erber
Ralf
R
Jonas
Jost B
JB
Hammes
Hans-Peter
HP
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation; D058449:Intravitreal Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000201:enzymology / Q000473:pathology; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013792:Thalidomide / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D053148:Caspase 3