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Intravitreal thalidomide reduces experimental preretinal neovascularization without induction of retinal toxicity
  1. Franziska vom Hagen1,
  2. Bernd A Kamppeter2,
  3. Ralf Erber3,
  4. Jost Jonas2,
  5. Hans-Peter Hammes1
  1. 1 Medical Department, Clinical Faculty Mannheim, University of Heidelberg, Germany;
  2. 2 Department of Ophthalmology, Medical Faculty Mannheim, University of Heidelberg, Germany;
  3. 3 Department of Neurosurgery, Medical Faculty Mannheim, University of Heidelberg, Germany
  1. To whom correspondence should be addressed. E-mail: hans-peter.hammes{at}med5.ma.uni-heidelberg.de

Abstract

Background/aims: Proliferative retinopathies have remained the most common causes of blindness. Retinal neovascularization 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 the reduction of VEGF. We investigated the effect of intravitreal application of thalidomide on neovascularization and retinal toxicity in a mouse model of proliferative retinopathy.

Methods: C57BL/6J mice were exposed to 75% oxygen from postnatal day 7 (p7) to 12. Immediately after transfer to room air at p12, mice received an intravitreal injection of 150µg/µl thalidomide or control solution. Preretinal neovascularization 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 neovascularization by 62% compared to 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 and neither retinal caspase-3 activity nor apoptotic cell counts were altered.

Conclusion: These data indicate that intravitreal application of thalidomide can be an effective and safe way to treat retinal neovascularization.

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